RECOMBINANT SYNTHESIS OF ALKANES

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is related to U.S. Provisional Application No. 61/756,973, filed January 25, 2013 and U.S. Provisional Application No. 61/826,637, filed May 23, 2013; each of which is herein incorporated by reference, in its entirety, for all purposes.

SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Month XX, 20XX, is named XXXXXUS_sequencelisting.txt, and is Χ,ΧΧΧ,ΧΧΧ bytes in size.

BACKGROUND

[0003] Many existing photoautotrophic organisms (i.e., plants, algae, and photosynthetic bacteria) are poorly suited for industrial bioprocessing and have therefore not demonstrated commercial viability. Recombinant photosynthetic microorganisms have been engineered to produce hydrocarbons and alcohols in amounts that exceed the levels produced naturally by the organism.

SUMMARY

[0004] Described herein is an engineered microorganism, wherein said engineered microorganism comprises one or more recombinant genes encoding one or more enzymes having enzyme activities which catalyze the production of alkanes, wherein the enzyme activities comprise: an alkane deformylative monooxygenase activity, a thioesterase activity, a carboxylic acid reductase activity, and a phosphopanthetheinyl transferase activity; an alkane deformylative monooxygenase activity, a thioesterase activity, a long-chain fatty acid CoA-ligase activity, and a long-chain acyl-CoA reductase activity; and/or an alkane deformylative monooxygenase activity, a pyruvate decarboxylase activity and a 2-ketoacid decarboxylase activity.

[0005] In some aspects, the enzymes comprise an alkane deformylative monooxygenase, a thioesterase, a carboxylic acid reductase, and a phosphopanthetheinyl transferase. In some aspects, the alkane deformylative monooxygenase has EC number 4.1.99.5, the thioesterase has EC number 3.1.2.14, the carboxylic acid reductase has EC number 1.2.99.6, and the phosphopanthetheinyl transferase has EC number 2.7.8.7. In some aspects, the alkane deformylative monooxygenase is encoded by adm, the thioesterase is encoded by fatB or fatB2, the carboxylic acid reductase is encoded by carB, and the phosphopanthetheinyl transferase is encoded by entD.

[0006] In some aspects, the enzyme having alkane deformylative monooxygenase activity has EC number 4.1.99.5. In some aspects, the enzyme having thioesterase activity has EC number 3.1.2.14. In some aspects, the enzyme having carboxylic acid reductase activity has EC number 1.2.99.6. In some aspects, the enzyme having phosphopanthetheinyl transferase activity has EC number 2.7.8.7.

[0007] In some aspects, the enzymes comprise an alkane deformylative monooxygenase, a thioesterase, a long-chain fatty acid CoA-ligase, and a long-chain acyl-CoA reductase. In some aspects, the alkane deformylative monooxygenase has EC number 4.1.99.5, the thioesterase has EC number 3.1.2.14, the long-chain fatty acid CoA-ligase has EC number 6.2.1.3, and the long-chain acyl-CoA reductase has EC number 1.2.1.50. In some aspects, the alkane deformylative monooxygenase is encoded by adm, the thioesterase is encoded by fatB or fatB2, the long-chain fatty acid CoA-ligase is encoded by fadD, and the long-chain acyl- CoA reductase is encoded by acrM.

[0008] In some aspects, the enzyme having alkane deformylative monooxygenase activity has EC number 4.1.99.5. In some aspects, the enzyme having thioesterase activity has EC number 3.1.2.14. In some aspects, the enzyme having long-chain fatty acid CoA-ligase activity has EC number 6.2.1.3. In some aspects, the enzyme having long-chain acyl-CoA reductase activity has EC number 1.2.1.50.

[0009] In some aspects, the one or more recombinant genes comprise a recombinant gene encoding a thioesterase that catalyzes the conversion of acyl-ACP to a fatty acid. In some aspects, the one or more recombinant genes comprises a recombinant gene encoding a phosphopanthetheinyl transferase that phosphopatetheinylates the ACP moiety of a protein encoded by a carboxylic acid reductase gene. In some aspects, the one or more recombinant genes comprise a recombinant gene encoding a carboxylic acid reductase that catalyzes the conversion of fatty acid to fatty aldehyde. In some aspects, the one or more recombinant genes comprise a recombinant gene encoding a alkane deformylative monooxygenase that catalyzes the conversion of fatty aldehyde to an alkane or alkene. In some aspects, the one or more recombinant genes comprise a recombinant gene encoding a fatty acid CoA-ligase that catalyzes the conversion of fatty acid to acyl-CoA. In some aspects, the one or more recombinant genes comprise a recombinant gene encoding an acyl-CoA reductase that catalyzes the conversion of acyl-CoA to fatty aldehyde. [0010] In some aspects, the enzymes comprise an alkane deformylative monooxygenase, a pyruvate decarboxylase and a 2-ketoacid decarboxylase.

[0011] In some aspects, said microorganism is a bacterium. In some aspects, said microorganism is a gram-negative bacterium. In some aspects, said microorganism is E. coli.

[0012] In some aspects, said microorganism is a photosynthetic microorganism. In some aspects, said microorganism is a cyanobacterium. In some aspects, said microorganism is a thermotolerant cyanobacterium. In some aspects, said microorganism is a Synechococcus species.

[0013] In some aspects, expression of an operon comprising the one or more recombinant genes is controlled by a recombinant promoter, and wherein the promoter is constitutive or inducible. In some aspects, said operon is integrated into the genome of said microorganism. In some aspects, said operon is extrachromosomal.

[0014] In some aspects, said alkanes are less than or equal to 11 carbon atoms in length. In some aspects, said alkanes are 7 to 11 carbon atoms in length. In some aspects, said alkanes are 7, 8, 9, 10, or 11 carbon atoms in length. In some aspects, said alkanes are less than or equal to 18 carbon atoms in length. In some aspects, said alkanes are 7 to 18 carbon atoms in length. In some aspects, said alkanes are 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbon atoms in length.

[0015] In some aspects, said recombinant genes are at least 90% or at least 95% identical to a sequence shown in the Tables.

[0016] Also described herein is a cell culture comprising a culture medium and a microorganism described herein.

[0017] Also described herein is a method for producing hydrocarbons, comprising:

culturing an engineered microorganism described herein in a culture medium, wherein said engineered microorganism produces increased amounts of alkanes relative to an otherwise identical microorganism, cultured under identical conditions, but lacking said recombinant genes. In some aspects, the method further includes allowing alkanes to accumulate in the culture medium or in the organism. In some aspects, the method further includes isolating at least a portion of the alkanes. In some aspects, the method further includes processing the isolated alkanes to produce a processed material.

[0018] Also described herein is a method for producing hydrocarbons, comprising: (i) culturing an engineered microorganism described herein in a culture medium; and (ii) exposing said engineered microorganism to light and inorganic carbon, wherein said exposure results in the conversion of said inorganic carbon by said microorganism into alkanes, wherein said alkanes are produced in an amount greater than that produced by an otherwise identical microorganism, cultured under identical conditions, but lacking said recombinant genes. In some aspects, the method further includes allowing alkanes to accumulate in the culture medium or in the organism. In some aspects, the method further includes isolating at least a portion of the alkanes. In some aspects, the method further includes processing the isolated alkanes to produce a processed material.

[0019] Also described herein is a composition comprising alkanes, wherein said alkanes are produced by a method described herein. In some aspects, the composition comprises at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, or at least 99% alkanes.

[0020] The present invention provides, in certain embodiments a method of producing a short-chain alkane or alkene from an engineered organism, the method comprising:

expressing a recombinant alkanal deformylative monooxygenase ("ADM") in the engineered microorganism; culturing the engineered microorganism in a culture medium containing a carbon source under conditions effective to produce a short-chain alkane or alkene.

[0021] In an embodiment, ADM catalyzes the conversion of an aldehyde into an alkane or alkene, wherein the aldehyde is selected from the group consisting of acetaldehyde, butanal, propanal, isobutanal, butanal, 3 -methyl- 1-butanal and 2-phenylethanal. In an embodiment, the alkane or alkene is selected from the group consisting of methane, propane, ethane, butane, propane, isobutane and toluene. In an embodiment, the method of producing a short-chain alkane or alkene from an engineered organism comprises expressing a recombinant pyruvate decarboxylase ("Pdc") in the engineered microorganism. In certain embodiments, the Pdc is at least 90% identical SEQ ID NO: 46. In an embodiment, the method of producing a short-chain alkane or alkene from an engineered organism comprises expressing a 2-ketoacid decarboxylase in the engineered microorganism. In certain embodiments, the Pdc or the 2-ketoacid decarboxylase are expressed in an operon under the control of a single promoter.

[0022] In an embodiment, the operon comprises ADM. In certain embodiments, the ADM is at least 90% identical to SEQ ID NO: 36.

[0023] Also provided herein, are embodiments comprising an engineered microorganism, wherein the engineered microorganism comprises a recombinant gene encoding an alkanal deformylative monooxygenase ("ADM"), and wherein the engineered microorganism further comprises a recombinant gene encoding an enzyme selected from the group consisting of: pyruvate decarboxylase and 2-ketoacid decarboxylase. [0024] In one embodiment, the ADM catalyzes the conversion of an aldehyde into an alkane or alkene, wherein the aldehyde is selected from the group consisting of acetaldehyde, butanal, propanal, isobutanal, 2 -methyl- 1 -butanal, butanal, 3 -methyl- 1 -butanal and 2- phenylethanal. In certain embodiments, the alkane or alkene is selected from the group consisting of methane, propane, ethane, butane, propane, isobutane and toluene.

[0025] In one embodiment, the engineered microorganism comprises a recombinant pyruvate decarboxylase ("Pdc"). In certain embodiments, the Pdc is at least 90% identical to SEQ ID NO: 46. In one embodiment, the engineered microorganism comprises a 2-ketoacid decarboxylase. In certain embodiments, the Pdc or the 2-ketoacid decarboxylase are expressed in an operons under the control of a single promoter.

[0026] In one embodiment, the operon comprises ADM. In some embodiments, the engineered microorganism is an engineered cyanobacterium. In certain embodiments, the ADM is at least 90% identical to SEQ ID NO: 36.

[0027] Also provided herein, are embodiments comprising a cell culture comprising a recombinant microorganism and a culture medium containing a carbon source, wherein a polypeptide that catalyzes the conversion of an aldehyde to an alkane is overexpressed in the recombinant microorganism and an alkane or alkene is produced in the cell culture when the recombinant microorganism is cultured in the culture medium under conditions effective to express the polypeptide. In an embodiment, the polypeptide has alkanal deformylative monooxygenase activity. In an embodiment, the polypeptide comprises an amino acid sequence having at least 90%> identity to SEQ ID NO: 36. In some embodiments, the aldehyde is selected from the group consisting of acetaldehyde, butanal, propanal, isobutanal, butanal, 3 -methyl- 1 -butanal, and 2-phenylethanal.

[0028] In an embodiment, the alkane or alkene is selected from the group consisting of methane, propane, ethane, butane, propane, isobutane, and toluene. In an embodiment, the alkane is a short-chain alkane. In certain embodiments, the alkane comprises a C ₂ to C ₄ alkane. In some embodiments, the alkane comprises a C ₂ to C ₇ alkane. In an embodiment, the alkane or the alkene is secreted into the culture medium.

[0029] In an embodiment, the recombinant microorganism further comprises a recombinant polypeptide comprising a pyruvate decarboxylase ("Pdc") activity. In certain embodiments, the Pdc is at least 90% identical to SEQ ID NO: 46. In an embodiment, the recombinant microorganism further comprises a recombinant 2-ketoacid decarboxylase. In some embodiments, the Pdc or the 2-ketoacid decarboxylase are expressed in an operon under the control of a single promoter. In an embodiment, the operon comprises ADM. [0030] In an embodiment, the recombinant microorganism is selected from the group consisting of yeast, fungi, filamentous fungi, algae, and bacterium. In some embodiments, the bacterium is a cyanobacterium.

[0031] Also provided herein, are embodiments comprising a method for producing isobutane or a derivative of isobutane, comprising contacting ADM with an aldehyde in vitro. In an embodiment, the ADM is at least 90% identical to SEQ ID NO: 36. In certain embodiments, the ADM is Nostoc punctiforme ADM. In an embodiment, the aldehyde is 3- methy lbutyraldehy de .

[0032] These and other embodiments of the invention are further described in the Figures, Description, Examples and Claims, herein.

BRIEF DESCRIPTION OF THE FIGURES

[0033] Figure 1. SDS-PAGE gel showing the overexpression of AcrM protein in E. coli.

[0034] Figure 2. TIC chromatograms of assays with (A) decanoyl-CoA, (B) lauroyl-CoA. Solid line: wild type BL21(DE3); dotted line: acr -expressing BL21(DE3).

[0035] Figure 3. GC/FID chromatogram showing the detection of C13 and C15 alkanes produced by Synechococcus sp. PCC 7002 strain expressing Adm, CarB, TesA and EntD proteins. Grey trace: control strain (does not express CarB protein); solid black trace:

Standards of C13, C14, and C15 n-alkanes; dashed black trace: Synechococcus sp. PCC 7002 strain expressing Adm, CarB, TesA, and EntD proteins.

[0036] Figure 4. TIC chromatograms of samples from acid-fed (dashed lines) or control (solid lines) Synechococcus sp. PCC 7002 expressing Adm and CarB. A and D: octanoic acid feeding, B and E: decanoic acid feeding, C and F: dodecanoic acid feeding.

[0037] Figure 5. GC/FID chromatogram showing the detection of nonane produced by Synechococcus sp. PCC 7002 strain expressing Adm, CarB, FatB2 and EntD proteins at 12h and 72h. Solid trace: control strain (wild type); dotted trace: Synechococcus sp. PCC 7002 strain expressing Adm, CarB, FatB2, and EntD proteins.

[0038] Figure 6. Examples of pathways for production of alkanes. Note that the use of carB can be facilitated by the product of entD (phosphopatetheinyl transferase), which phosphopatethemylates the ACP moiety of the CarB protein. For example, one can use the Bacillus entD, whose enzyme product has a wide substrate spectrum that includes CarB.

[0039] Figure 7. Detection of nonane (A) and undecane (B) produced by Synechococcus sp. PCC 7002 strain expressing Adm, thioesterase, CarB, and EntD proteins when fed with decanoic acid and dodecanoic acid. Circles: alkane detected in the cell pellet; triangles:

alkane detected in the hexadecane overlay.

[0040] Figure 8. GC/FID chromatograms showing the biosynthesis of nonane (A) and undecane (B) from C0 ₂ , by Synechococcus sp. PCC 7002 strain expressing Adm, thioesterase, CarB, and EntD proteins, secreted into the hexadecane overlay. Solid trace: samples from day 0; dotted trace: samples from day 5.

[0041] Figure 9. Time course of the biosynthesis of undecane (triangle) and nonane (circle) from C0 ₂ , by Synechococcus sp. PCC 7002 strain expressing Adm, thioesterase, CarB, and EntD proteins, secreted into the hexadecane overlay.

[0042] Figure 10. GC/FID chromatogram showing the detection of C13 and C15 alkanes produced by 7002 strain expressing Adm, CarB, TesA _m and EntD proteins. Solid line: control strain; dotted line: ALK-C13C15 (experimental strain).

[0043] Figure 11. The growth curve of ALK-C 13C15 over 10 days.

[0044] Figure 12. The production curve of tridecane and pentadecane by ALK-C 13C 15 over 10 days.

[0045] Figure 13. Depicts fractions from Ni-NTA purification of His ₆ -tagged ADM enzyme. The collected fractions pooled for assay use are indicated.

[0046] Figure 14. Time course of the biosynthesis of undecane (triangle) from C0 ₂ by

JCC6036.

[0047] Figure 15. Detection of nonane produced by 7002 strain expressing Adm, CarB, and EntD proteins when fed with decanoic acid. By expressing Nhistagged Adm on pAQ3, the initial activity was increased significantly compared to that on pAQ4.

DETAILED DESCRIPTION

[0048] Unless otherwise defined herein, scientific and technical terms used in connection with the present invention shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular. Generally, nomenclatures used in connection with, and techniques of, biochemistry, enzymology, molecular and cellular biology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well known and commonly used in the art.

[0049] The methods and techniques of the present invention are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated. See, e.g., Sambrook et al., Molecular Cloning: A Laboratory Manual, 2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989); Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates (1992, and Supplements to 2002); Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1990); Taylor and Drickamer,

Introduction to Glycobiology, Oxford Univ. Press (2003); Worthington Enzyme Manual, Worthington Biochemical Corp., Freehold, N.J.; Handbook of Biochemistry: Section A Proteins, Vol I, CRC Press (1976); Handbook of Biochemistry: Section A Proteins, Vol II, CRC Press (1976); Essentials of Glycobiology, Cold Spring Harbor Laboratory Press (1999).

[0050] All publications, patents and other references mentioned herein are hereby incorporated by reference in their entireties.

[0051] The following terms, unless otherwise indicated, shall be understood to have the following meanings:

[0052] The term "polynucleotide" or "nucleic acid molecule" refers to a polymeric form of nucleotides of at least 10 bases in length. The term includes DNA molecules {e.g., cDNA or genomic or synthetic DNA) and RNA molecules {e.g. , mRNA or synthetic RNA), as well as analogs of DNA or RNA containing non-natural nucleotide analogs, non-native

intemucleoside bonds, or both. The nucleic acid can be in any topological conformation. For instance, the nucleic acid can be single-stranded, double-stranded, triple-stranded, quadruplexed, partially double-stranded, branched, hairpinned, circular, or in a padlocked conformation.

[0053] Unless otherwise indicated, and as an example for all sequences described herein under the general format "SEQ ID NO:", "nucleic acid comprising SEQ ID NO: l" refers to a nucleic acid, at least a portion of which has either (i) the sequence of SEQ ID NO: 1 , or (ii) a sequence complementary to SEQ ID NO: 1. The choice between the two is dictated by the context. For instance, if the nucleic acid is used as a probe, the choice between the two is dictated by the requirement that the probe be complementary to the desired target.

[0054] An "isolated" RNA, DNA or a mixed polymer is one which is substantially separated from other cellular components that naturally accompany the native polynucleotide in its natural host cell, e.g., ribosomes, polymerases and genomic sequences with which it is naturally associated.

[0055] As used herein, an "isolated" organic molecule (e.g., an alkane) is one which is substantially separated from the cellular components (membrane lipids, chromosomes, proteins) of the host cell from which it originated, or from the medium in which the host cell was cultured. The term does not require that the biomolecule has been separated from all other chemicals, although certain isolated biomolecules may be purified to near homogeneity.

[0056] The term "recombinant" refers to a biomolecule, e.g., a gene or protein, that (1) has been removed from its naturally occurring environment, (2) is not associated with all or a portion of a polynucleotide in which the gene is found in nature, (3) is operatively linked to a polynucleotide which it is not linked to in nature, or (4) does not occur in nature. The term "recombinant" can be used in reference to cloned DNA isolates, chemically synthesized polynucleotide analogs, or polynucleotide analogs that are biologically synthesized by heterologous systems, as well as proteins and/or mR As encoded by such nucleic acids.

[0057] As used herein, an endogenous nucleic acid sequence in the genome of an organism (or the encoded protein product of that sequence) is deemed "recombinant" herein if a heterologous sequence is placed adjacent to the endogenous nucleic acid sequence, such that the expression of this endogenous nucleic acid sequence is altered. In this context, a heterologous sequence is a sequence that is not naturally adjacent to the endogenous nucleic acid sequence, whether or not the heterologous sequence is itself endogenous (originating from the same host cell or progeny thereof) or exogenous (originating from a different host cell or progeny thereof). By way of example, a promoter sequence can be substituted (e.g., by homologous recombination) for the native promoter of a gene in the genome of a host cell, such that this gene has an altered expression pattern. This gene would now become

"recombinant" because it is separated from at least some of the sequences that naturally flank it.

[0058] A nucleic acid is also considered "recombinant" if it contains any modifications that do not naturally occur to the corresponding nucleic acid in a genome. For instance, an endogenous coding sequence is considered "recombinant" if it contains an insertion, deletion or a point mutation introduced artificially, e.g., by human intervention. A "recombinant nucleic acid" also includes a nucleic acid integrated into a host cell chromosome at a heterologous site and a nucleic acid construct present as an episome.

[0059] As used herein, the phrase "degenerate variant" of a reference nucleic acid sequence encompasses nucleic acid sequences that can be translated, according to the standard genetic code, to provide an amino acid sequence identical to that translated from the reference nucleic acid sequence. The term "degenerate oligonucleotide" or "degenerate primer" is used to signify an oligonucleotide capable of hybridizing with target nucleic acid sequences that are not necessarily identical in sequence but that are homologous to one another within one or more particular segments. [0060] The term "percent sequence identity" or "identical" in the context of nucleic acid sequences refers to the residues in the two sequences which are the same when aligned for maximum correspondence. The length of sequence identity comparison may be over a stretch of at least about nine nucleotides, usually at least about 20 nucleotides, more usually at least about 24 nucleotides, typically at least about 28 nucleotides, more typically at least about 32 nucleotides, and preferably at least about 36 or more nucleotides. There are a number of different algorithms known in the art which can be used to measure nucleotide sequence identity. For instance, polynucleotide sequences can be compared using FASTA, Gap or Bestfit, which are programs in Wisconsin Package Version 10.0, Genetics Computer Group (GCG), Madison, Wis. FASTA provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences. Pearson, Methods Enzymol. 183:63-98 (1990) (hereby incorporated by reference in its entirety). For instance, percent sequence identity between nucleic acid sequences can be determined using FASTA with its default parameters (a word size of 6 and the NOP AM factor for the scoring matrix) or using Gap with its default parameters as provided in GCG Version 6.1, herein incorporated by reference. Alternatively, sequences can be compared using the computer program, BLAST (Altschul et al, J. Mol. Biol. 215:403-410 (1990); Gish and States, Nature Genet. 3:266-272 (1993); Madden et al, Meth. Enzymol. 266: 131-141 (1996); Altschul et al, Nucleic Acids Res. 25:3389-3402 (1997); Zhang and Madden, Genome Res. 7:649-656 (1997)), especially blastp or tblastn (Altschul et al, Nucleic Acids Res. 25:3389-3402 (1997)).

[0061] The term "substantial homology" or "substantial similarity," when referring to a nucleic acid or fragment thereof, indicates that, when optimally aligned with appropriate nucleotide insertions or deletions with another nucleic acid (or its complementary strand), there is nucleotide sequence identity in at least about 76%, 80%, 85%>, preferably at least about 90%, and more preferably at least about 95%, 96%, 97%, 98% or 99% of the nucleotide bases, as measured by any well-known algorithm of sequence identity, such as FASTA, BLAST or Gap, as discussed above.

[0062] Alternatively, substantial homology or similarity exists when a nucleic acid or fragment thereof hybridizes to another nucleic acid, to a strand of another nucleic acid, or to the complementary strand thereof, under stringent hybridization conditions. "Stringent hybridization conditions" and "stringent wash conditions" in the context of nucleic acid hybridization experiments depend upon a number of different physical parameters. Nucleic acid hybridization will be affected by such conditions as salt concentration, temperature, solvents, the base composition of the hybridizing species, length of the complementary regions, and the number of nucleotide base mismatches between the hybridizing nucleic acids, as will be readily appreciated by those skilled in the art. One having ordinary skill in the art knows how to vary these parameters to achieve a particular stringency of

hybridization.

[0063] In general, "stringent hybridization" is performed at about 25°C below the thermal melting point (T _m ) for the specific DNA hybrid under a particular set of conditions.

"Stringent washing" is performed at temperatures about 5°C lower than the T _m for the specific DNA hybrid under a particular set of conditions. The T _m is the temperature at which 50% of the target sequence hybridizes to a perfectly matched probe. See Sambrook et al., Molecular Cloning: A Laboratory Manual, 2d ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (1989), page 9.51, hereby incorporated by reference. For purposes herein, "stringent conditions" are defined for solution phase hybridization as aqueous hybridization (i.e., free of formamide) in 6xSSC (where 20xSSC contains 3.0 M NaCl and 0.3 M sodium citrate), 1% SDS at 65°C for 8-12 hours, followed by two washes in 0.2xSSC, 0.1% SDS at 65°C for 20 minutes. It will be appreciated by the skilled worker that hybridization at 65°C will occur at different rates depending on a number of factors including the length and percent identity of the sequences which are hybridizing.

[0064] The nucleic acids (also referred to as polynucleotides) of this present invention may include both sense and antisense strands of RNA, cDNA, genomic DNA, and synthetic forms and mixed polymers of the above. They may be modified chemically or biochemically or may contain non-natural or derivatized nucleotide bases, as will be readily appreciated by those of skill in the art. Such modifications include, for example, labels, methylation, substitution of one or more of the naturally occurring nucleotides with an analog, intemucleotide modifications such as uncharged linkages (e.g., methyl phosphonates, phosphotriesters, phosphoramidates, carbamates, etc.), charged linkages (e.g.,

phosphorothioates, phosphorodithioates, etc.), pendent moieties (e.g., polypeptides), intercalators (e.g., acridine, psoralen, etc.), chelators, alkylators, and modified linkages (e.g., alpha anomeric nucleic acids, etc.) Also included are synthetic molecules that mimic polynucleotides in their ability to bind to a designated sequence via hydrogen bonding and other chemical interactions. Such molecules are known in the art and include, for example, those in which peptide linkages substitute for phosphate linkages in the backbone of the molecule. Other modifications can include, for example, analogs in which the ribose ring contains a bridging moiety or other structure such as the modifications found in "locked" nucleic acids. [0065] The term "mutated" when applied to nucleic acid sequences means that nucleotides in a nucleic acid sequence may be inserted, deleted or changed compared to a reference nucleic acid sequence. A single alteration may be made at a locus (a point mutation) or multiple nucleotides may be inserted, deleted or changed at a single locus. In addition, one or more alterations may be made at any number of loci within a nucleic acid sequence. A nucleic acid sequence may be mutated by any method known in the art including but not limited to mutagenesis techniques such as "error-prone PCR" (a process for performing PCR under conditions where the copying fidelity of the DNA polymerase is low, such that a high rate of point mutations is obtained along the entire length of the PCR product; see, e.g. , Leung et al., Technique, 1 :11-15 (1989) and Caldwell and Joyce, PCR Methods Applic. 2:28- 33 (1992)); and "oligonucleotide-directed mutagenesis" (a process which enables the generation of site-specific mutations in any cloned DNA segment of interest; see, e.g., Reidhaar-Olson and Sauer, Science 241 :53-57 (1988)).

[0066] The term "attenuate" as used herein generally refers to a functional deletion, including a mutation, partial or complete deletion, insertion, or other variation made to a gene sequence or a sequence controlling the transcription of a gene sequence, which reduces or inhibits production of the gene product, or renders the gene product non-functional. In some instances a functional deletion is described as a knockout mutation. Attenuation also includes amino acid sequence changes by altering the nucleic acid sequence, placing the gene under the control of a less active promoter, down-regulation, expressing interfering RNA, ribozymes or antisense sequences that target the gene of interest, or through any other technique known in the art. In one example, the sensitivity of a particular enzyme to feedback inhibition or inhibition caused by a composition that is not a product or a reactant (non-pathway specific feedback) is lessened such that the enzyme activity is not impacted by the presence of a compound. In other instances, an enzyme that has been altered to be less active can be referred to as attenuated.

[0067] Deletion: The removal of one or more nucleotides from a nucleic acid molecule or one or more amino acids from a protein, the regions on either side being joined together.

[0068] Knock-out: A gene whose level of expression or activity has been reduced to zero. In some examples, a gene is knocked-out via deletion of some or all of its coding sequence. In other examples, a gene is knocked-out via introduction of one or more nucleotides into its open reading frame, which results in translation of a non-sense or otherwise non-functional protein product. [0069] The term "vector" as used herein is intended to refer to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a "plasmid," which generally refers to a circular double stranded DNA loop into which additional DNA segments may be ligated, but also includes linear double-stranded molecules such as those resulting from amplification by the polymerase chain reaction (PCR) or from treatment of a circular plasmid with a restriction enzyme. Other vectors include cosmids, bacterial artificial chromosomes (BAC) and yeast artificial chromosomes (YAC). Another type of vector is a viral vector, wherein additional DNA segments may be ligated into the viral genome (discussed in more detail below). Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., vectors having an origin of replication which functions in the host cell). Other vectors can be integrated into the genome of a host cell upon introduction into the host cell, and are thereby replicated along with the host genome. Moreover, certain preferred vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as

"recombinant expression vectors" (or simply "expression vectors").

[0070] "Operatively linked" or "operably linked" expression control sequences refers to a linkage in which the expression control sequence is contiguous with the gene of interest to control the gene of interest, as well as expression control sequences that act in trans or at a distance to control the gene of interest.

[0071] The term "expression control sequence" as used herein refers to polynucleotide sequences which are necessary to affect the expression of coding sequences to which they are operatively linked. Expression control sequences are sequences which control the transcription, post-transcriptional events and translation of nucleic acid sequences.

Expression control sequences include appropriate transcription initiation, termination, promoter and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (e.g., ribosome binding sites); sequences that enhance protein stability; and when desired, sequences that enhance protein secretion. The nature of such control sequences differs depending upon the host organism; in prokaryotes, such control sequences generally include promoter, ribosomal binding site, and transcription termination sequence. The term "control sequences" is intended to include, at a minimum, all components whose presence is essential for expression, and can also include additional components whose presence is advantageous, for example, leader sequences and fusion partner sequences. [0072] The term "recombinant host cell" (or simply "host cell"), as used herein, is intended to refer to a cell into which a recombinant vector has been introduced. It should be understood that such terms are intended to refer not only to the particular subject cell but to the progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term "host cell" as used herein. A recombinant host cell may be an isolated cell or cell line grown in culture or may be a cell which resides in a living tissue or organism.

[0073] The term "peptide" as used herein refers to a short polypeptide, e.g., one that is typically less than about 50 amino acids long and more typically less than about 30 amino acids long. The term as used herein encompasses analogs and mimetics that mimic structural and thus biological function.

[0074] The term "polypeptide" encompasses both naturally-occurring and non-naturally- occurring proteins, and fragments, mutants, derivatives and analogs thereof. A polypeptide may be monomeric or polymeric. Further, a polypeptide may comprise a number of different domains each of which has one or more distinct activities.

[0075] The term "isolated protein" or "isolated polypeptide" is a protein or polypeptide that by virtue of its origin or source of derivation (1) is not associated with naturally associated components that accompany it in its native state, (2) exists in a purity not found in nature, where purity can be adjudged with respect to the presence of other cellular material {e.g., is free of other proteins from the same species) (3) is expressed by a cell from a different species, or (4) does not occur in nature {e.g., it is a fragment of a polypeptide found in nature or it includes amino acid analogs or derivatives not found in nature or linkages other than standard peptide bonds). Thus, a polypeptide that is chemically synthesized or synthesized in a cellular system different from the cell from which it naturally originates will be "isolated" from its naturally associated components. A polypeptide or protein may also be rendered substantially free of naturally associated components by isolation, using protein purification techniques well known in the art. As thus defined, "isolated" does not necessarily require that the protein, polypeptide, peptide or oligopeptide so described has been physically removed from its native environment.

[0076] The term "polypeptide fragment" as used herein refers to a polypeptide that has a deletion, e.g., an amino-terminal and/or carboxy-terminal deletion compared to a full-length polypeptide. In a preferred embodiment, the polypeptide fragment is a contiguous sequence in which the amino acid sequence of the fragment is identical to the corresponding positions in the naturally-occurring sequence. Fragments typically are at least 5, 6, 7, 8, 9 or 10 amino acids long, preferably at least 12, 14, 16 or 18 amino acids long, more preferably at least 20 amino acids long, more preferably at least 25, 30, 35, 40 or 45, amino acids, even more preferably at least 50 or 60 amino acids long, and even more preferably at least 70 amino acids long.

[0077] A "modified derivative" refers to polypeptides or fragments thereof that are substantially homologous in primary structural sequence but which include, e.g. , in vivo or in vitro chemical and biochemical modifications or which incorporate amino acids that are not found in the native polypeptide. Such modifications include, for example, acetylation, carboxylation, phosphorylation, glycosylation, ubiquitination, labeling, e.g., with

radionuclides, and various enzymatic modifications, as will be readily appreciated by those skilled in the art. A variety of methods for labeling polypeptides and of substituents or labels useful for such purposes are well known in the art, and include radioactive isotopes such as

125 32 35 3

I, P, S, and H, ligands which bind to labeled antiligands {e.g., antibodies),

fluorophores, chemiluminescent agents, enzymes, and antiligands which can serve as specific binding pair members for a labeled ligand. The choice of label depends on the sensitivity required, ease of conjugation with the primer, stability requirements, and available instrumentation. Methods for labeling polypeptides are well known in the art. See, e.g., Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates (1992, and Supplements to 2002) (hereby incorporated by reference).

[0078] The term "fusion protein" refers to a polypeptide comprising a polypeptide or fragment coupled to heterologous amino acid sequences. Fusion proteins are useful because they can be constructed to contain two or more desired functional elements from two or more different proteins. A fusion protein comprises at least 10 contiguous amino acids from a polypeptide of interest, more preferably at least 20 or 30 amino acids, even more preferably at least 40, 50 or 60 amino acids, yet more preferably at least 75, 100 or 125 amino acids. Fusions that include the entirety of the proteins of the present invention have particular utility. The heterologous polypeptide included within the fusion protein of the present invention is at least 6 amino acids in length, often at least 8 amino acids in length, and usefully at least 15, 20, and 25 amino acids in length. Fusions that include larger

polypeptides, such as an IgG Fc region, and even entire proteins, such as the green fluorescent protein ("GFP") chromophore-containing proteins, have particular utility. Fusion proteins can be produced recombinantly by constructing a nucleic acid sequence which encodes the polypeptide or a fragment thereof in frame with a nucleic acid sequence encoding a different protein or peptide and then expressing the fusion protein. Alternatively, a fusion protein can be produced chemically by crosslinking the polypeptide or a fragment thereof to another protein.

[0079] The term "non-peptide analog" refers to a compound with properties that are analogous to those of a reference polypeptide. A non-peptide compound may also be termed a "peptide mimetic" or a "peptidomimetic." See, e.g., Jones, Amino Acid and Peptide Synthesis, Oxford University Press (1992); Jung, Combinatorial Peptide and Nonpeptide Libraries: A Handbook, John Wiley (1997); Bodanszky et al., Peptide Chemistry— A

Practical Textbook, Springer Verlag (1993); Synthetic Peptides: A Users Guide, (Grant, ed., W. H. Freeman and Co., 1992); Evans et al, J. Med. Chem. 30:1229 (1987); Fauchere, J. Adv. Drug Res. 15:29 (1986); Veber and Freidinger, Trends Neurosci., 8:392-396 (1985); and references sited in each of the above, which are incorporated herein by reference. Such compounds are often developed with the aid of computerized molecular modeling. Peptide mimetics that are structurally similar to useful peptides of the present invention may be used to produce an equivalent effect and are therefore envisioned to be part of the present invention.

[0080] A "polypeptide mutant" or "mutein" refers to a polypeptide whose sequence contains an insertion, duplication, deletion, rearrangement or substitution of one or more amino acids compared to the amino acid sequence of a native or wild-type protein. A mutein may have one or more amino acid point substitutions, in which a single amino acid at a position has been changed to another amino acid, one or more insertions and/or deletions, in which one or more amino acids are inserted or deleted, respectively, in the sequence of the naturally-occurring protein, and/or truncations of the amino acid sequence at either or both the amino or carboxy termini. A mutein may have the same but preferably has a different biological activity compared to the naturally-occurring protein.

[0081] A mutein has at least 85% overall sequence homology to its wild-type counterpart. Even more preferred are muteins having at least 90% overall sequence homology to the wild- type protein.

[0082] In an even more preferred embodiment, a mutein exhibits at least 95% sequence identity, even more preferably 98%, even more preferably 99% and even more preferably 99.9%) overall sequence identity.

[0083] Sequence homology may be measured by any common sequence analysis algorithm, such as Gap or Bestfit. [0084] Amino acid substitutions can include those which: (1) reduce susceptibility to proteolysis, (2) reduce susceptibility to oxidation, (3) alter binding affinity for forming protein complexes, (4) alter binding affinity or enzymatic activity, and (5) confer or modify other physicochemical or functional properties of such analogs.

[0085] As used herein, the twenty conventional amino acids and their abbreviations follow conventional usage. See Immunology-A Synthesis (Golub and Gren eds., Sinauer Associates, Sunderland, Mass., 2 ^nd ed. 1991), which is incorporated herein by reference. Stereoisomers (e.g., D-amino acids) of the twenty conventional amino acids, unnatural amino acids such as α-, α-disubstituted amino acids, N-alkyl amino acids, and other unconventional amino acids may also be suitable components for polypeptides of the present invention. Examples of unconventional amino acids include: 4-hydroxyproline, γ-carboxyglutamate, ε-Ν,Ν,Ν- trimethyllysine, ε-Ν-acetyllysine, O-phosphoserine, N-acetylserine, N-formylmethionine, 3- methylhistidine, 5-hydroxylysine, N-methylarginine, and other similar amino acids and imino acids (e.g., 4-hydroxyproline). In the polypeptide notation used herein, the left-hand end corresponds to the amino terminal end and the right-hand end corresponds to the carboxy- terminal end, in accordance with standard usage and convention.

[0086] A protein has "homology" or is "homologous" to a second protein if the nucleic acid sequence that encodes the protein has a similar sequence to the nucleic acid sequence that encodes the second protein. Alternatively, a protein has homology to a second protein if the two proteins have "similar" amino acid sequences. (Thus, the term "homologous proteins" is defined to mean that the two proteins have similar amino acid sequences.) As used herein, homology between two regions of amino acid sequence (especially with respect to predicted structural similarities) is interpreted as implying similarity in function.

[0087] When "homologous" is used in reference to proteins or peptides, it is recognized that residue positions that are not identical often differ by conservative amino acid substitutions. A "conservative amino acid substitution" is one in which an amino acid residue is substituted by another amino acid residue having a side chain (R group) with similar chemical properties (e.g., charge or hydrophobicity). In general, a conservative amino acid substitution will not substantially change the functional properties of a protein. In cases where two or more amino acid sequences differ from each other by conservative

substitutions, the percent sequence identity or degree of homology may be adjusted upwards to correct for the conservative nature of the substitution. Means for making this adjustment are well known to those of skill in the art. See, e.g., Pearson, 1994, Methods Mol. Biol.

24:307-31 and 25:365-89 (herein incorporated by reference). [0088] The following six groups each contain amino acids that are conservative substitutions for one another: 1) Serine (S), Threonine (T); 2) Aspartic Acid (D), Glutamic Acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Alanine (A), Valine (V), and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W).

[0089] Sequence homology for polypeptides, which is also referred to as percent sequence identity, is typically measured using sequence analysis software. See, e.g., the Sequence Analysis Software Package of the Genetics Computer Group (GCG), University of Wisconsin Biotechnology Center, 910 University Avenue, Madison, Wis. 53705. Protein analysis software matches similar sequences using a measure of homology assigned to various substitutions, deletions and other modifications, including conservative amino acid substitutions. For instance, GCG contains programs such as "Gap" and "Bestfit" which can be used with default parameters to determine sequence homology or sequence identity between closely related polypeptides, such as homologous polypeptides from different species of organisms or between a wild-type protein and a mutein thereof. See, e.g., GCG Version 6.1.

[0090] A preferred algorithm when comparing a particular polypeptide sequence to a database containing a large number of sequences from different organisms is the computer program BLAST (Altschul et al, J. Mol. Biol. 215:403-410 (1990); Gish and States, Nature Genet. 3:266-272 (1993); Madden et al, Meth. Enzymol. 266:131-141 (1996); Altschul et al, Nucleic Acids Res. 25:3389-3402 (1997); Zhang and Madden, Genome Res. 7:649-656 (1997)), especially blastp or tblastn (Altschul et al, Nucleic Acids Res. 25:3389-3402

(1997)).

[0091] Preferred parameters for BLASTp are: Expectation value: 10 (default); Filter: seg (default); Cost to open a gap: 11 (default); Cost to extend a gap: 1 (default); Max. alignments: 100 (default); Word size: 11 (default); No. of descriptions: 100 (default); Penalty Matrix: BLOWSUM62.

[0092] The length of polypeptide sequences compared for homology will generally be at least about 16 amino acid residues, usually at least about 20 residues, more usually at least about 24 residues, typically at least about 28 residues, and preferably more than about 35 residues. When searching a database containing sequences from a large number of different organisms, it is preferable to compare amino acid sequences. Database searching using amino acid sequences can be measured by algorithms other than blastp known in the art. For instance, polypeptide sequences can be compared using FASTA, a program in GCG Version 6.1. FAST A provides alignments and percent sequence identity of the regions of the best overlap between the query and search sequences. Pearson, Methods Enzymol. 183:63-98 (1990) (incorporated by reference herein). For example, percent sequence identity between amino acid sequences can be determined using FASTA with its default parameters (a word size of 2 and the PAM250 scoring matrix), as provided in GCG Version 6.1, herein incorporated by reference.

[0093] "Specific binding" refers to the ability of two molecules to bind to each other in preference to binding to other molecules in the environment. Typically, "specific binding" discriminates over adventitious binding in a reaction by at least two-fold, more typically by at least 10-fold, often at least 100-fold. Typically, the affinity or avidity of a specific binding reaction, as quantified by a dissociation constant, is about 10 ^"7 M or stronger {e.g., about 10 ^"8 M, 10 ^"9 M or even stronger).

[0094] The term "region" as used herein refers to a physically contiguous portion of the primary structure of a biomolecule. In the case of proteins, a region is defined by a contiguous portion of the amino acid sequence of that protein.

[0095] The term "domain" as used herein refers to a structure of a biomolecule that contributes to a known or suspected function of the biomolecule. Domains may be coextensive with regions or portions thereof; domains may also include distinct, non-contiguous regions of a biomolecule. Examples of protein domains include, but are not limited to, an Ig domain, an extracellular domain, a transmembrane domain, and a cytoplasmic domain.

[0096] As used herein, the term "molecule" means any compound, including, but not limited to, a small molecule, peptide, protein, sugar, nucleotide, nucleic acid, lipid, etc., and such a compound can be natural or synthetic.

[0097] "Carbon-based Products of Interest" include alcohols such as ethanol, propanol, isopropanol, butanol, fatty alcohols, fatty acid esters, wax esters; hydrocarbons and alkanes such as propane, octane, diesel, Jet Propellant 8 (JP8); polymers such as terephthalate, 1,3-propanediol, 1,4-butanediol, polyols, Polyhydroxyalkanoates (PHA), poly-beta- hydroxybutyrate (PHB), acrylate, adipic acid, ε-caprolactone, isoprene, caprolactam, rubber; commodity chemicals such as lactate, Docosahexaenoic acid (DHA), 3-hydroxypropionate, γ-valerolactone, lysine, serine, aspartate, aspartic acid, sorbitol, ascorbate, ascorbic acid, isopentenol, lanosterol, omega-3 DHA, lycopene, itaconate, 1,3-butadiene, ethylene, propylene, succinate, citrate, citric acid, glutamate, malate, 3-hydroxypropionic acid (HP A), lactic acid, THF, gamma butyrolactone, pyrrolidones, hydroxybutyrate, glutamic acid, levulinic acid, acrylic acid, malonic acid; specialty chemicals such as carotenoids, isoprenoids, itaconic acid; pharmaceuticals and pharmaceutical intermediates such as 7- aminodeacetoxycephalosporanic acid (7-ADCA)/cephalosporin, erythromycin, polyketides, statins, paclitaxel, docetaxel, terpenes, peptides, steroids, omega fatty acids and other such suitable products of interest. Such products are useful in the context of bio fuels, industrial and specialty chemicals, as intermediates used to make additional products, such as nutritional supplements, neutraceuticals, polymers, paraffin replacements, personal care products and pharmaceuticals.

[0098] Biofuel: A biofuel refers to any fuel that derives from a biological source. Biofuel can refer to one or more hydrocarbons, one or more alcohols (such as ethanol), one or more fatty esters, or a mixture thereof.

[0099] Hydrocarbon: The term generally refers to a chemical compound that consists of the elements carbon (C), hydrogen (H) and optionally oxygen (O). There are essentially three types of hydrocarbons, e.g., aromatic hydrocarbons, saturated hydrocarbons and unsaturated hydrocarbons such as alkenes, alkynes, and dienes. The term also includes fuels, biofuels, plastics, waxes, solvents and oils. Hydrocarbons encompass biofuels, as well as plastics, waxes, solvents and oils.

[00100] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this present invention pertains. Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can also be used in the practice of the present invention and will be apparent to those of skill in the art. All publications and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. The materials, methods, and examples are illustrative only and not intended to be limiting.

[00101] Throughout this specification and claims, the word "comprise" or variations such as "comprises" or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

Nucleic Acid Sequences

[00102] The present invention provides isolated nucleic acid molecules for genes encoding enzymes, and variants thereof. Exemplary full-length nucleic acid sequences for genes encoding enzymes and the corresponding amino acid sequences are presented in Tables 1 and 2. [00103] In one embodiment, the present invention provides an isolated nucleic acid molecule having a nucleic acid sequence comprising or consisting of a gene coding for an alkane deformylative monooxygenase, a thioesterase, a carboxylic acid reductase, a phosphopanthetheinyl transferase, a long-chain fatty acid CoA-ligase, and/or a long-chain acyl-CoA reductase and homologs, variants and derivatives thereof expressed in a host cell of interest. The present invention also provides a nucleic acid molecule comprising or consisting of a sequence which is a codon-optimized version of the alkane deformylative monooxygenase, a thioesterase, a carboxylic acid reductase, a phosphopanthetheinyl transferase, a long-chain fatty acid CoA-ligase, and/or a long-chain acyl-CoA reductase genes described herein. In a further embodiment, the present invention provides a nucleic acid molecule and homologs, variants and derivatives of the molecule comprising or consisting of a sequence which is a variant of the alkane deformylative monooxygenase, a thioesterase, a carboxylic acid reductase, a phosphopanthetheinyl transferase, a long-chain fatty acid CoA- ligase, and/or a long-chain acyl-CoA reductase gene having at least 80% identity to the wild- type gene. The nucleic acid sequence can be preferably greater than 80%>, 85%, 90%>, 95%, 98%), 99%), 99.9%) or even higher identity to the wild-type gene.

[00104] In another embodiment, the nucleic acid molecule of the present invention encodes a polypeptide having an amino acid sequence disclosed in Tables 1 and 2. Preferably, the nucleic acid molecule of the present invention encodes a polypeptide sequence of at least 50%, 60, 70%, 80%, 85%, 90% or 95% identity to the amino acid sequences shown in Tables 1 and 2 and the identity can even more preferably be 96%>, 97%, 98%>, 99%, 99.9% or even higher.

[00105] The present invention also provides nucleic acid molecules that hybridize under stringent conditions to the above-described nucleic acid molecules. As defined above, and as is well known in the art, stringent hybridizations are performed at about 25°C below the thermal melting point (T _m ) for the specific DNA hybrid under a particular set of conditions, where the T _m is the temperature at which 50% of the target sequence hybridizes to a perfectly matched probe. Stringent washing is performed at temperatures about 5°C lower than the T _m for the specific DNA hybrid under a particular set of conditions.

[00106] Nucleic acid molecules comprising a fragment of any one of the above-described nucleic acid sequences are also provided. These fragments preferably contain at least 20 contiguous nucleotides. More preferably the fragments of the nucleic acid sequences contain at least 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100 or even more contiguous nucleotides. [00107] The nucleic acid sequence fragments of the present invention display utility in a variety of systems and methods. For example, the fragments may be used as probes in various hybridization techniques. Depending on the method, the target nucleic acid sequences may be either DNA or RNA. The target nucleic acid sequences may be fractionated (e.g., by gel electrophoresis) prior to the hybridization, or the hybridization may be performed on samples in situ. One of skill in the art will appreciate that nucleic acid probes of known sequence find utility in determining chromosomal structure (e.g., by Southern blotting) and in measuring gene expression (e.g., by Northern blotting). In such experiments, the sequence fragments are preferably detectably labeled, so that their specific hydridization to target sequences can be detected and optionally quantified. One of skill in the art will appreciate that the nucleic acid fragments of the present invention may be used in a wide variety of blotting techniques not specifically described herein.

[00108] It should also be appreciated that the nucleic acid sequence fragments disclosed herein also find utility as probes when immobilized on microarrays. Methods for creating microarrays by deposition and fixation of nucleic acids onto support substrates are well known in the art. Reviewed in DNA Microarrays: A Practical Approach (Practical Approach Series), Schena (ed.), Oxford University Press (1999) (ISBN: 0199637768); Nature Genet. 21(l)(suppl): l-60 (1999); Microarray Biochip: Tools and Technology, Schena (ed.), Eaton Publishing Company/BioTechniques Books Division (2000) (ISBN: 1881299376), the disclosures of which are incorporated herein by reference in their entireties. Analysis of, for example, gene expression using microarrays comprising nucleic acid sequence fragments, such as the nucleic acid sequence fragments disclosed herein, is a well-established utility for sequence fragments in the field of cell and molecular biology. Other uses for sequence fragments immobilized on microarrays are described in Gerhold et al., Trends Biochem. Sci. 24: 168-173 (1999) and Zweiger, Trends Biotechnol. 17:429-436 (1999); DNA Microarrays: A Practical Approach (Practical Approach Series), Schena (ed.), Oxford University Press (1999) (ISBN: 0199637768); Nature Genet. 21(l)(suppl): l-60 (1999); Microarray Biochip: Tools and Technology, Schena (ed.), Eaton Publishing Company/BioTechniques Books Division (2000) (ISBN: 1881299376), the disclosure of each of which is incorporated herein by reference in its entirety.

[00109] As is well known in the art, enzyme activities can be measured in various ways. For example, the pyrophosphorolysis of OMP may be followed spectroscopically

(Grubmeyer et al., (1993) J. Biol. Chem. 268:20299-20304). Alternatively, the activity of the enzyme can be followed using chromatographic techniques, such as by high performance liquid chromatography (Chung and Sloan, (1986) J. Chromatogr. 371 :71-81). As another alternative the activity can be indirectly measured by determining the levels of product made from the enzyme activity. These levels can be measured with techniques including aqueous chloroform/methanol extraction as known and described in the art (Cf. M. Kates (1986) Techniques ofLipidology; Isolation, analysis and identification of Lipids. Elsevier Science Publishers, New York (ISBN: 0444807322)). More modern techniques include using gas chromatography linked to mass spectrometry (Niessen, W. M. A. (2001). Current practice of gas chromatography— mass spectrometry. New York, NY: Marcel Dekker. (ISBN:

0824704738)). Additional modern techniques for identification of recombinant protein activity and products including liquid chromatography-mass spectrometry (LCMS), high performance liquid chromatography (HPLC), capillary electrophoresis, Matrix-Assisted Laser Desorption Ionization time of flight-mass spectrometry (MALDI-TOF MS), nuclear magnetic resonance (NMR), near-infrared (NIR) spectroscopy, viscometry (Knothe, G (1997) Am. Chem. Soc. Symp. Series, 666: 172-208), titration for determining free fatty acids (Komers (1997) Fett/Lipid, 99(2): 52-54), enzymatic methods (Bailer (1991) Fresenius J. Anal. Chem. 340(3): 186), physical property-based methods, wet chemical methods, etc. can be used to analyze the levels and the identity of the product produced by the organisms of the present invention. Other methods and techniques may also be suitable for the measurement of enzyme activity, as would be known by one of skill in the art.

Vectors

[00110] Also provided are vectors, including expression vectors, which comprise the above nucleic acid molecules of the present invention, as described further herein. In a first embodiment, the vectors include the isolated nucleic acid molecules described above. In an alternative embodiment, the vectors of the present invention include the above-described nucleic acid molecules operably linked to one or more expression control sequences. The vectors of the instant invention may thus be used to express a polypeptide contributing to alkane producing activity by a host cell.

[00111] Vectors useful for expression of nucleic acids in prokaryotes are well known in the art.

Isolated Polypeptides

[00112] According to another aspect of the present invention, isolated polypeptides (including muteins, allelic variants, fragments, derivatives, and analogs) encoded by the nucleic acid molecules of the present invention are provided. In one embodiment, the isolated polypeptide comprises the polypeptide sequence corresponding to a polypeptide sequence shown in Table 1 or 2. In an alternative embodiment of the present invention, the isolated polypeptide comprises a polypeptide sequence at least 85% identical to a polypeptide sequence shown in Table 1 or 2. Preferably the isolated polypeptide of the present invention has at least 50%, 60, 70%, 80%, 85%, 90%, 95%, 98%, 98.1%, 98.2%, 98.3%, 98.4%, 98.5%, 98.6%, 98.7%, 98.8%, 98.9%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%), 99.8%), 99.9%) or even higher identity to a polypeptide sequence shown in Table 1 or 2.

[00113] According to other embodiments of the present invention, isolated polypeptides comprising a fragment of the above-described polypeptide sequences are provided. These fragments preferably include at least 20 contiguous amino acids, more preferably at least 25, 30, 35, 40, 45, 50, 60, 70, 80, 90, 100 or even more contiguous amino acids.

[00114] The polypeptides of the present invention also include fusions between the above- described polypeptide sequences and heterologous polypeptides. The heterologous sequences can, for example, include sequences designed to facilitate purification, e.g. histidine tags, and/or visualization of recombinantly-expressed proteins. Other non-limiting examples of protein fusions include those that permit display of the encoded protein on the surface of a phage or a cell, fusions to intrinsically fluorescent proteins, such as green fluorescent protein (GFP), and fusions to the IgG Fc region.

Host Cell Transformants

[00115] In another aspect of the present invention, host cells transformed with the nucleic acid molecules or vectors of the present invention, and descendants thereof, are provided. In some embodiments of the present invention, these cells carry the nucleic acid sequences of the present invention on vectors, which may but need not be freely replicating vectors. In other embodiments of the present invention, the nucleic acids have been integrated into the genome of the host cells.

[00116] In an alternative embodiment, the host cells of the present invention can be mutated by recombination with a disruption, deletion or mutation of the isolated nucleic acid of the present invention so that the activity of one or more enzyme(s) in the host cell is reduced or eliminated compared to a host cell lacking the mutation. Selected or Engineered Microorganisms For the Production of Carbon-Based Products of Interest

[00117] Microorganism: Includes prokaryotic and eukaryotic microbial species from the Domains Archaea, Bacteria and Eucarya, the latter including yeast and filamentous fungi, protozoa, algae, or higher Protista. The terms "microbial cells" and "microbes" are used interchangeably with the term microorganism.

[00118] A variety of host organisms can be transformed to produce a product of interest. Photoautotrophic organisms include eukaryotic plants and algae, as well as prokaryotic cyanobacteria, green-sulfur bacteria, green non-sulfur bacteria, purple sulfur bacteria, and purple non-sulfur bacteria.

[00119] Extremophiles are also contemplated as suitable organisms. Such organisms withstand various environmental parameters such as temperature, radiation, pressure, gravity, vacuum, desiccation, salinity, pH, oxygen tension, and chemicals. They include

hyperthermophiles, which grow at or above 80°C such as Pyrolobus fumarii; thermophiles, which grow between 60-80°C such as Synechococcus lividis; mesophiles, which grow between 15-60°C and psychrophiles, which grow at or below 15°C such as Psychrobacter and some insects. Radiation tolerant organisms include Deinococcus radiodurans . Pressure- tolerant organisms include piezophiles, which tolerate pressure of 130 MPa. Weight-tolerant organisms include barophiles. Hypergravity {e.g.,, >lg) hypogravity {e.g., <lg) tolerant organisms are also contemplated. Vacuum tolerant organisms include tardigrades, insects, microbes and seeds. Dessicant tolerant and anhydrobiotic organisms include xerophiles such as Artemia salina; nematodes, microbes, fungi and lichens. Salt-tolerant organisms include halophiles {e.g., 2-5 M NaCl) Halobacteriacea and Dunaliella salina. pH-tolerant organisms include alkaliphiles such as Natronobacterium, Bacillus firmus OF4, Spirulina spp. {e.g. , pH > 9) and acidophiles such as Cyanidium caldarium, Ferroplasma sp. {e.g., low pH).

Anaerobes, which cannot tolerate 0 ₂ such as Methanococcus jannaschii; microaerophils, which tolerate some 0 ₂ such as Clostridium and aerobes, which require 0 ₂ are also contemplated. Gas-tolerant organisms, which tolerate pure C0 ₂ include Cyanidium caldarium and metal tolerant organisms include metalotolerants such as Ferroplasma acidarmanus {e.g., Cu, As, Cd, Zn), Ralstonia sp. CH34 {e.g., Zn, Co, Cd, Hg, Pb). Gross, Michael. Life on the Edge: Amazing Creatures Thriving in Extreme Environments. New York: Plenum (1998) and Seckbach, J. "Search for Life in the Universe with Terrestrial Microbes Which Thrive Under Extreme Conditions." In Cristiano Batalli Cosmovici, Stuart Bowyer, and Dan Wertheimer, eds., Astronomical and Biochemical Origins and the Search or Life in the Universe, p. 511. Milan: Editrice Compositori (1997).

[00120] Plants include but are not limited to the following genera: Arabidopsis, Beta, Glycine, Jatropha, Miscanthus, Panicum, Phalaris, Populus, Saccharum, Salix, Simmondsia and Zea.

[00121] Algae and cyanobacteria include but are not limited to the following genera:

Acanthoceras, Acanthococcus, Acaryochloris, Achnanthes, Achnanthidium, Actinastrum, Actinochloris, Actinocyclus, Actinotaenium, Amphichrysis, Amphidinium, Amphikrikos, Amphipleura, Amphiprora, Amphithrix, Amphora, Anabaena, Anabaenopsis, Aneumastus, Ankistrodesmus, Ankyra, Anomoeoneis, Apatococcus, Aphanizomenon, Aphanocapsa, Aphanochaete, Aphanothece, Apiocystis, Apistonema, Arthrodesmus, Artherospira,

Ascochloris, Asterionella, Asterococcus, Audouinella, Aulacoseira, Bacillaria, Balbiania, Bambusina, Bangia, Basichlamys, Batrachospermum, Binuclearia, Bitrichia, Blidingia, Botrdiopsis, Botrydium, Botryococcus, Botryosphaerella, Brachiomonas, Brachysira, Brachytrichia, Brebissonia, Bulbochaete, Bumilleria, Bumilleriopsis, Caloneis, Calothrix, Campylodiscus, Capsosiphon, Carteria, Catena, Cavinula, Centritr actus, Centronella, Ceratium, Chaetoceros, Chaetochloris, Chaetomorpha, Chaetonella, Chaetonema,

Chaetopeltis, Chaetophora, Chaetosphaeridium, Chamaesiphon, Chara, Characiochloris, Characiopsis, Characium, Charales, Chilomonas, Chlainomonas, Chlamydoblepharis, Chlamydocapsa, Chlamydomonas, Chlamydomonopsis, Chlamydomyxa, Chlamydonephris, Chlorangiella, Chlorangiopsis, Chlorella, Chlorobotrys, Chlorobrachis, Chlorochytrium, Chlorococcum, Chlorogloea, Chlorogloeopsis, Chlorogonium, Chlorolobion, Chloromonas, Chlorophysema, Chlorophyta, Chlorosaccus, Chlorosarcina, Choricystis, Chromophyton, Chromulina, Chroococcidiopsis, Chroococcus, Chroodactylon, Chroomonas, Chroothece, Chrysamoeba, Chrysapsis, Chrysidiastrum, Chrysocapsa, Chrysocapsella, Chrysochaete, Chrysochromulina, Chrysococcus, Chrysocrinus, Chrysolepidomonas, Chrysolykos,

Chrysonebula, Chrysophyta, Chrysopyxis, Chrysosaccus, Chrysophaerella,

Chrysostephanosphaera, Clodophora, Clastidium, Closteriopsis, Closterium, Coccomyxa, Cocconeis, Coelastrella, Coelastrum, Coelosphaerium, Coenochloris, Coenococcus,

Coenocystis, Colacium, Coleochaete, Collodictyon, Compsogonopsis, Compsopogon, Conjugatophyta, Conochaete, Coronastrum, Cosmarium, Cosmioneis, Cosmocladium, Crateriportula, Craticula, Crinalium, Crucigenia, Crucigeniella, Cryptoaulax, Cryptomonas, Cryptophyta, Ctenophora, Cyanodictyon, Cyanonephron, Cyanophora, Cyanophyta,

Cyanothece, Cyanothomonas, Cyclonexis, Cyclostephanos, Cyclotella, Cylindrocapsa, Cylindrocystis, Cylindrospermum, Cylindrotheca, Cymatopleura, Cymbella, Cymbellonitzschia, Cystodinium Dactylococcopsis, Debarya, Denticula, Dermatochrysis, Dermocarpa, Dermocarpella, Desmatractum, Desmidium, Desmococcus, Desmonema, Desmosiphon, Diacanthos, Diacronema, Diadesmis, Diatoma, Diatomella, Dicellula, Dichothrix, Dichotomococcus, Dicranochaete, Dictyochloris, Dictyococcus,

Dictyosphaerium, Didymocystis, Didymogenes, Didymosphenia, Dilabifilum,

Dimorphococcus, Dinobryon, Dinococcus, Diplochloris, Diploneis, Diplostauron,

Distrionella, Docidium, Draparnaldia, Dunaliella, Dysmorphococcus, Ecballocystis, Elakatothrix, EUerbeckia, Encyonema, Enter omorpha, Entocladia, Entomoneis,

Entophysalis, Epichrysis, Epipyxis, Epithemia, Eremosphaera, Euastropsis, Euastrum, Eucapsis, Eucocconeis, Eudorina, Euglena, Euglenophyta, Eunotia, Eustigmatophyta, Eutreptia, Fallacia, Fischerella, Fragilaria, Fragilariforma, Franceia, Frustulia, Curcilla, Geminella, Genicularia, Glaucocystis, Glaucophyta, Glenodiniopsis, Glenodinium,

Gloeocapsa, Gloeochaete, Gloeochrysis, Gloeococcus, Gloeocystis, Gloeodendron, Gloeomonas, Gloeoplax, Gloeothece, Gloeotila, Gloeotrichia, Gloiodictyon, Golenkinia, Golenkiniopsis, Gomontia, Gomphocymbella, Gomphonema, Gomphosphaeria,

Gonatozygon, Gongrosia, Gongrosira, Goniochloris, Gonium, Gonyostomum,

Granulochloris, Granulocystopsis, Groenbladia, Gymnodinium, Gymnozyga, Gyrosigma, Haematococcus, Hafniomonas, Hallassia, Hammatoidea, Hannaea, Hantzschia,

Hapalosiphon, Haplotaenium, Haptophyta, Haslea, Hemidinium, Hemitoma, Heribaudiella, Heteromastix, Heterothrix, Hibberdia, Hildenbrandia, Hillea, Holopedium, Homoeothrix, Hormanthonema, Hormotila, Hyalobrachion, Hyalocardium, Hyalodiscus, Hyalogonium, Hyalotheca, Hydrianum, Hydrococcus, Hydrocoleum, Hydrocoryne, Hydrodictyon, Hydrosera, Hydrurus, Hyella, Hymenomonas, Isthmochloron, Johannesbaptistia,

Juranyiella, Karayevia, Kathablepharis, Katodinium, Kephyrion, Keratococcus,

Kirchneriella, Klebsormidium, Kolbesia, Koliella, Komarekia, Korshikoviella, Kraskella, Lagerheimia, Lagynion, Lamprothamnium, Lemanea, Lepocinclis, Leptosira, Lobococcus, Lobocystis, Lobomonas, Luticola, Lyngbya, Malleochloris, Mallomonas, Mantoniella, Marssoniella, Martyana, Mastigocoleus, Gastogloia, Melosira, Merismopedia, Mesostigma, Mesotaenium, Micractinium, Micrasterias, Microchaete, Microcoleus, Microcystis, Microglena, Micromonas, Microspora, Microthamnion, Mischococcus, Monochrysis, Monodus, Monomastix, Monoraphidium, Monostroma, Mougeotia, Mougeotiopsis,

Myochloris, Myromecia, Myxosarcina, Naegeliella, Nannochloris, Nautococcus, Navicula, Neglectella, Neidium, Nephroclamys, Nephrocytium, Nephrodiella, Nephroselmis, Netrium, Nitella, Nitellopsis, Nitzschia, Nodularia, Nostoc, Ochromonas, Oedogonium, Oligochaetophora, Onychonema, Oocardium, Oocystis, Opephora, Ophiocytium, Orthoseira, Oscillatoria, Oxyneis, Pachycladella, Palmella, Palmodictyon, Pnadorina, Pannus, Paralia, Pascherina, Paulschulzia, Pediastrum, Pedinella, Pedinomonas, Pedinopera, Pelagodictyon, Penium, Peranema, Peridiniopsis, Peridinium, Peronia, Petroneis, Phacotus, Phacus, Phaeaster, Phaeodermatium, Phaeophyta, Phaeosphaera, Phaeothamnion, Phormidium, Phycopeltis, Phyllariochloris, Phyllocardium, Phyllomitas, Pinnularia, Pitophora, Placoneis, Planctonema, Planktosphaeria, Planothidium, Plectonema, Pleodorina, Pleurastrum, Pleurocapsa, Pleurocladia, Pleurodiscus, Pleurosigma, Pleurosira, Pleurotaenium,

Pocillomonas, Podohedra, Polyblepharides, Polychaetophora, Polyedriella, Polyedriopsis, Polygoniochloris, Polyepidomonas, Polytaenia, Polytoma, Polytomella, Porphyridium, Posteriochromonas, Prasinochloris, Prasinocladus, Prasinophyta, Prasiola, Prochlorphyta, Prochlorothrix, Protoderma, Protosiphon, Provasoliella, Prymnesium, Psammodictyon, Psammothidium, Pseudanabaena, Pseudenoclonium, Psuedocarteria, Pseudochate,

Pseudocharacium, Pseudococcomyxa, Pseudodictyosphaerium, Pseudokephyrion,

Pseudoncobyrsa, Pseudoquadrigula, Pseudosphaerocystis, Pseudostaurastrum,

Pseudostaurosira, Pseudotetrastrum, Pteromonas, Punctastruata, Pyramichlamys,

Pyramimonas, Pyrrophyta, Quadrichloris, Quadricoccus, Quadrigula, Radiococcus,

Radiofilum, Raphidiopsis, Raphidocelis, Raphidonema, Raphidophyta, Peimeria,

Rhabdoderma, Rhabdomonas, Rhizoclonium, Rhodomonas, Rhodophyta, Rhoicosphenia, Rhopalodia, Rivularia, Rosenvingiella, Rossithidium, Roya, Scenedesmus, Scherffelia, Schizochlamydella, Schizochlamys, Schizomeris, Schizothrix, Schroederia, Scolioneis, Scotiella, Scotiellopsis, Scourfieldia, Scytonema, Selenastrum, Selenochloris, Sellaphora, Semiorbis, Siderocelis, Diderocystopsis, Dimonsenia, Siphononema, Sirocladium,

Sirogonium, Skeletonema, Sorastrum, Spermatozopsis, Sphaerellocystis, Sphaerellopsis, Sphaerodinium, Sphaeroplea, Sphaerozosma, Spiniferomonas, Spirogyra, Spirotaenia, Spirulina, Spondylomorum, Spondylosium, Sporotetras, Spumella, Staurastrum,

Stauerodesmus, Stauroneis, Staurosira, Staurosirella, Stenopterobia, Stephanocostis, Stephanodiscus, Stephanoporos, Stephanosphaera, Stichococcus, Stichogloea, Stigeoclonium, Stigonema, Stipitococcus, Stokesiella, Strombomonas, Stylochrysalis, Stylodinium, Styloyxis, Stylosphaeridium, Surirella, Sykidion, Symploca, Synechococcus, Synechocystis, Synedra, Synochromonas, Synura, Tabellaria, Tabularia, Teilingia, Temnogametum, Tetmemorus, Tetrachlorella, Tetracyclus, Tetradesmus, Tetraedriella, Tetraedron, Tetraselmis,

Tetraspora, Tetrastrum, Thalassiosira, Thamniochaete, Thorakochloris, Thorea, Tolypella, Tolypothrix, Trachelomonas, Trachydiscus, Trebouxia, Trentepholia, Treubaria, Tribonema, Trichodesmium, Trichodiscus, Trochiscia, Tryblionella, Ulothrix, Uroglena, Uronema, Urosolenia, Urospora, Uva, Vacuolaria, Vaucheria, Volvox, Volvulina, Westella,

Woloszynskia, Xanthidium, Xanthophyta, Xenococcus, Zygnema, Zygnemopsis, and

Zygonium. Cyanobacteria include members of the genus Chamaesiphon, Chroococcus, Cyanobacterium, Cyanobium, Cyanothece, Dactylococcopsis, Gloeobacter, Gloeocapsa, Gloeothece, Microcystis, Prochlorococcus, Prochloron, Synechococcus, Synechocystis, Cyanocystis, Dermocarpella, Stanieria, Xenococcus, Chroococcidiopsis, Myxosarcina, Arthrospira, Borzia, Crinalium, Geitlerinemia, Leptolyngbya, Limnothrix, Lyngbya,

Microcoleus, Oscillatoria, Planktothrix, Prochiorothrix, Pseudanabaena, Spirulina, Starria, Symploca, Trichodesmium, Tychonema, Anabaena, Anabaenopsis, Aphanizomenon,

Cyanospira, Cylindrospermopsis, Cylindrospermum, Nodularia, Nostoc, Scylonema, Calothrix, Rivularia, Tolypothrix, Chlorogloeopsis, Fischerella, Geitieria, Iyengariella, Nostochopsis, Stigonema and Thermosynechococcus .

[00122] Green non-sulfur bacteria include but are not limited to the following genera: Chloroflexus, Chloronema, Oscillochloris, Heliothrix, Herpetosiphon, Roseiflexus, and Thermomicrobium.

[00123] Green sulfur bacteria include but are not limited to the following genera:

[00124] Chlorobium, Clathrochloris, and Prosthecochloris.

[00125] Purple sulfur bacteria include but are not limited to the following genera:

Allochromatium, Chromatium, Halochromatium, Isochromatium, Marichromatium,

Rhodovulum, Thermochromatium, Thiocapsa, Thiorhodococcus, and Thiocystis,

[00126] Purple non-sulfur bacteria include but are not limited to the following genera: Phaeospirillum, Rhodobaca, Rhodobacter, Rhodomicrobium, Rhodopila,

Rhodopseudomonas, Rhodothalassium, Rhodospirillum, Rodovibrio, and Roseospira.

[00127] Aerobic chemolithotrophic bacteria include but are not limited to nitrifying bacteria such as Nitrobacteraceae sp., Nitrobacter sp., Nitrospina sp., Nitrococcus sp., Nitrospira sp., Nitrosomonas sp., Nitrosococcus sp., Nitrosospira sp., Nitrosolobus sp., Nitrosovibrio sp.; colorless sulfur bacteria such as, Thiovulum sp., Thiobacillus sp., Thiomicrospira sp., Thiosphaera sp., Thermothrix sp.; obligately chemolithotrophic hydrogen bacteria such as Hydrogenobacter sp., iron and manganese-oxidizing and/or depositing bacteria such as Siderococcus sp., and magnetotactic bacteria such as Aquaspirillum sp.

[00128] Archaeobacteria include but are not limited to methanogenic archaeobacteria such as Methanobacterium sp., Methanobrevibacter sp., Methanothermus sp., Methanococcus sp., Methanomicrobium sp., Methanospirillum sp., Methanogenium sp., Methanosarcina sp., Methanolobus sp., Methanothrix sp., Methanococcoides sp., Methanoplanus sp.; extremely thermophilic S-Metabolizers such as Thermoproteus sp., Pyrodictium sp., Sulfolobus sp., Acidianus sp. and other microorganisms such as, Bacillus subtilis, Saccharomyces cerevisiae, Streptomyces sp., Ralstonia sp., Rhodococcus sp., Corymb acteria sp., Brevibacteria sp., Mycobacteria sp., and oleaginous yeast.

[00129] Preferred organisms for the manufacture of alkanes according to the methods discloused herein include: Arabidopsis thaliana, Panicum virgatum, Miscanthus giganteus, and Zea mays (plants); Botryococcus braunii, Chlamydomonas reinhardtii and Dunaliela salina (algae); Synechococcus sp PCC 7002, Synechococcus sp. PCC 7942, Synechocystis sp. PCC 6803, Thermosynechococcus elongatus BP-1 (cyanobacteria); Chlorobium tepidum (green sulfur bacteria), Chloroflexus auranticus (green non-sulfur bacteria); Chromatium tepidum and Chromatium vinosum (purple sulfur bacteria); Rhodospirillum rubrum,

Rhodobacter capsulatus, and Rhodopseudomonas palusris (purple non-sulfur bacteria).

[00130] Yet other suitable organisms include synthetic cells or cells produced by synthetic genomes as described in Venter et al. US Pat. Pub. No. 2007/0264688, and cell-like systems or synthetic cells as described in Glass et al. US Pat. Pub. No. 2007/0269862.

[00131] Still, other suitable organisms include microorganisms that can be engineered to fix carbon dioxide bacteria such as Escherichia coli, Acetobacter aceti, Bacillus subtilis, yeast and fungi such as Clostridium ljungdahlii, Clostridium thermocellum, Penicillium

chrysogenum, Pichia pastoris, Saccharomyces cerevisiae, Schizosaccharomyces pombe, Pseudomonas fluorescens, or Zymomonas mobilis.

[00132] A suitable organism for selecting or engineering is capable of autotrophic fixation of C0 ₂ to products. This would cover photosynthesis and methanogenesis. Acetogenesis, encompassing the three types of C0 ₂ fixation; Calvin cycle, acetyl-CoA pathway and reductive TCA pathway is also covered. The capability to use carbon dioxide as the sole source of cell carbon (autotrophy) is found in almost all major groups ofprokaryotes. The C0 ₂ fixation pathways differ between groups, and there is no clear distribution pattern of the four presently-known autotrophic pathways. See, e.g., Fuchs, G. 1989. Alternative pathways of autotrophic CO ₂ fixation, p. 365-382. In H. G. Schlegel, and B. Bowien (ed.), Autotrophic bacteria. Springer- Verlag, Berlin, Germany. The reductive pentose phosphate cycle

(Calvin-Bassham-Benson cycle) represents the C0 ₂ fixation pathway in almost all aerobic autotrophic bacteria, for example, the cyanobacteria. [00133] Alkane production via engineered cyanobacteria, e.g., a Synechococcus or

Thermosynechococcus species, is preferred. Other preferred organisms include

Synechocystis, Klebsiella oxytoca, Escherichia coli or Saccharomyces cerevisiae. Other prokaryotic, archaea and eukaryotic host cells are also encompassed within the scope of the present invention.

[00134] In some aspects, alkane production via a photosynthetic organism can be carried out using the compositions, materials, and methods described in: PCT/US2009/035937 (filed March 3, 2009); and PCT/US2009/055949 (filed September 3, 2009); each of which is herein incorporated by reference in its entirety, for all purposes.

Carbon-Based Products of Interest: Hydrocarbons & Alcohols

[00135] In various embodiments of the invention, desired hydrocarbons and/or alcohols of certain chain length or a mixture thereof can be produced. In certain aspects, the host cell produces at least one of the following carbon-based products of interest: alkanes such as heptane, nonane, tridecane, pentadecane, and/or undecane. In other aspects, the carbon chain length ranges from C ₂ to C ₂₀ , e.g., C ₂ , C ₃ , C ₄ , C ₅ , C ₆ , C _7j C _8j C ₉ , C ₁₀₎ Cn_ Ci ₂ _ Ci ₃ _ Ci ₄ _ C ₁₅₎ C _16, Ci ₇ Ci ₈ , Ci ₉ or C ₂₀ . Accordingly, the invention provides production of various chain lengths of alkanes suitable for use as fuels & chemicals.

[00136] In preferred aspects, the methods provide culturing host cells for direct product secretion for easy recovery without the need to extract biomass. These carbon-based products of interest are secreted directly into the medium. Since the invention enables production of various defined chain length of hydrocarbons and alcohols, the secreted products are easily recovered or separated. The products of the invention, therefore, can be used directly or used with minimal processing.

Fuel Compositions

[00137] In various embodiments, compositions produced by the methods of the invention are used as fuels. Such fuels comply with ASTM standards, for instance, standard specifications for diesel fuel oils D 975-09b, and Jet A, Jet A-l and Jet B as specified in ASTM Specification D. 1655-68. Fuel compositions may require blending of several products to produce a uniform product. The blending process is relatively straightforward, but the determination of the amount of each component to include in a blend is much more difficult. Fuel compositions may, therefore, include aromatic and/or branched hydrocarbons, for instance, 75% saturated and 25% aromatic, wherein some of the saturated hydrocarbons are branched and some are cyclic. Preferably, the methods of the invention produce an array of hydrocarbons, such as C2-C17 or C ₁₀ -C ₁₅ to alter cloud point. Furthermore, the compositions may comprise fuel additives, which are used to enhance the performance of a fuel or engine. For example, fuel additives can be used to alter the freezing/gelling point, cloud point, lubricity, viscosity, oxidative stability, ignition quality, octane level, and flash point. Fuels compositions may also comprise, among others, antioxidants, static dissipater, corrosion inhibitor, icing inhibitor, biocide, metal deactivator and thermal stability improver.

[00138] In addition to many environmental advantages of the invention such as C0 ₂ conversion and renewable source, other advantages of the fuel compositions disclosed herein include low sulfur content, low emissions, being free or substantially free of alcohol and having high cetane number.

Example 1: Crude extract of E. coli cells overexpressing acrM convert lauroyl-CoA to dodecanal and decanoyl-CoA to decanal.

[00139] Acinetobacter sp. M-l acyl coenzyme A reductase, acrM, was codon-optimized for E. coli expression and synthesized by DNA2.0 (Menlo Park, CA; SEQ ID NO. 1) with a Ndel site on the 5' end and an EcoRI site on the 3 'end. The obtained gene was subcloned into a pET28a vector (Novagen) by digestion with Ndel and EcoRI and subsequent ligation. The resulting plasmid, pET28a-acr (SEQ ID NO. 2), containing an N-terminal His ₆ -tagged acrM, was transformed into a BL21(DE3) E. coli strain purchased from New England Biolabs, which was subsequently grown with shaking in Luria-Bertani medium supplemented with 100 μg/mL of kanomycin in a volume of 1 L to OD ₆ oo = 0.8 before induction with 0.25 mM Isopropyl β-D-l-thiogalactopyranoside for 5 hours in a 2-L shaker flask at 37°C. An SDS-PAGE gel demonstrating the overexpression of AcrM protein in pET28a-acr containing BL21(DE3) E. coli cells is shown in Figure 1.

[00140] The E. coli cells containing overexpressed AcrM were collected by centrifugation, resuspended in HEPES buffer (100 mM HEPES, 10% glycerol, pH 7.5) at a 1 :3 (w/v) ratio and lysed by sonication. 200 of buffer solution containing 100 total lysate, 1 mM acyl- CoA, 3 mM NADH (Sigma- Aldrich), 100 mM HEPES, 10% glycerol at pH 7.5 was incubated at 37 °C for 30 min, extracted with 100 μΐ _^ ethyl acetate and analyzed by GC/MS equipped with a HP-5ms column (Agilent, Santa Clara, CA). Total ion chromatography (TIC) indicated the detection of aldehydes produced from corresponding acyl-CoA substrates by the AcrM-containing cell extract in the presence of supplemented NADH, as shown in Figure 2, indicating that AcrM is able to convert lauroyl-CoA to dodecanal and decanoyl-CoA to decanal. Example 2: Feeding fatty acid to Synechococcus sp. PCC 7002 strain expressing adm- carB-entD results in detection of corresponding aldehyde and alkane.

[00141] The carboxylic acid reductase (carB) gene (SEQ ID NO. 3) was PCR-amplified from Mycobacterium smegmatis and verified by sequencing with multiple primers by Genewiz (South Plainfield, NJ). Cyanothece adm, E. coli leaderless tesA and E. coli entD genes were codon-optimized for E. coli overexpression and synthesized by DNA 2.0 (Menlo Park, CA; SEQ ID NO. 4 and 5) with an individual ribosome binding site in front of each gene. All four genes were subcloned into a pUC19 vector containing an ammonia-repressible P(nir07) promoter (US Patent No. 7,955,820), upstream/downstream homology regions, and a spectinomycin marker. The resulting plasmid, pAQ3 P( r07)-adm-carB-tesA-entD-SpecR (SEQ ID NO. 6), was transformed into wild-type Synechococcus sp. PCC 7002 and segregated in the presence of spectinomycin.

[00142] The expression and activity of the Adm, CarB, TesA, and EntD proteins were demonstrated by detection of tridecane and pentadecane in the transformed Synechococcus sp. PCC 7002 strain by GC/FID (Figure 3).

[00143] The Synechococcus sp. PCC 7002 cultures were grown to OD ₇₃ o ~ 5 before 1 mM fatty acid (100 mM stock in ethanol) was added and were then shaken at 150 rpm, 37°C for ~ 3 hours in the absence (lauric acid feeding) or presence (octanoic acid and decanoic acid feeding) of a pentadecane overlay (6 mL culture with 1 mL overlay). The pentadecane overlay from the octanoic acid-fed culture (Figure 4A and 4D), or decanoic acid culture (Figure 4B and 4E) was analyzed by GC/MS equipped with an HP-5ms column. For the lauric acid feeding assay, 1 mL culture was extracted with 400 hexane by vortexing for 1 min before being analyzed by GC/MS (Figure 4C, 4F). Note that the pAQ3::P(nir07)-adm- carB-tesA-entD-SpecR expressing Synechococcus sp. PCC 7002 strain can produce a detectable level of undecane even without feeding dodecanoic acid. Adm and carB together is able to produce undecane in vivo.

Example 3: Synechococcus sp. PCC 7002 strain expressing adm-carB-fatB2-entD results in increased detection of nonane in pentadecane overlay.

[00144] The E. coli leaderless tesA of pAQ3::F(mr07)-adm-carB-tesA-entD-SpecR, was replaced by Cuphea hookeriana leaderless fatB2 (a medium-chain acyl-ACP thioesterase), which was codon-optimized for E. coli overexpression and synthesized by DNA 2.0 (Menlo Park, CA; SEQ ID NO. 7), with an individual ribosome binding site in front of the gene, a 5' Kpn I restriction site and a 3' Hind III restriction site. The resulting plasmid, pAQ3::P(nir07)- adm-carB-fatB2-entD-SpecR (SEQ ID NO. 8), was transformed into wild-type Synechococcus sp. PCC 7002 and segregated in the presence of spectinomycin.

[00145] The wild type Synechococcus sp. PCC 7002 and pAQ3 P( r07)-adm-carB-fatB2- entD-SpecR expressing Synechococcus sp. PCC 7002 cultures (35 mL) were grown in JB3.0 media (Table A below) to OD730 ~ 3 (in the presence of 2 mM urea) before a 10 mL pentadecane overlay was added.

[00146] The cultures were shaken at 150 rpm, 37°C for 3 more days continuously. 100 μΙ_, pentadecane overlay samples from each flask were taken 12 hours (Figure 5 A) or 72 hours (Figure 5B) after pentadecane addition, respectively, and analyzed directly by GC/FID equipped with a 20 meter hp-5ms column. An increase of nonane production was detected in the pAQ3 P( r07)-adm-carB-fatB2-entD-SpecR expressing Synechococcus sp. PCC 7002 cultures but not in the wild type control ones. A relative increase in octane and heptanes production was also detected in the pAQ3 P( r07)-adm-carB-fatB2-entD-SpecR expressing Synechococcus sp. PCC 7002 cultures. Adm, CarB and FatB2 together produced nonane in vivo. Shorter alkanes can also be produced via Adm-CarB pathway if shorter fatty acids are provided in vivo.

Example 4: Alkane Production

[00147] One or more recombinant genes encoding one or more enzymes having enzyme activities which catalyze the production of alkanes are identified and selected. The enzyme activities include: an alkane deformylative monooxygenase activity, a thioesterase activity, a carboxylic acid reductase activity, and a phosphopanthetheinyl transferase activity, a long- chain fatty acid CoA-ligase activity, and/or a long-chain acyl-CoA reductase activity. Such genes and enzymes can be those described in Tables 1 and 2.

[00148] The selected genes are cloned into an expression vector. For example, adm-carB- entD-fatB or adm-acrM-fadD-fatB (or combinations of homo logs thereof) are cloned into one or more vectors. See Figure 6. The genes can be under inducible control (such as the urea- repressible nir07 promoter or the cumate -inducible cum02 promoter). The genes may or may not be expressed operonically; and one or more of the genes can be placed under constitutive control such that when the other gene(s) are induced, the genes under constitutive control are already expressed. For example, one might express adm, carB, and entD constitutively while placing fatty-acid-generating fatB under inducible control; thus when fatty acids are made by fatB after induction, the remainder of the pathway is already present.

[00149] One or more vectors are selected and transformed into a microorganism (e.g., cyanobacteria). The cells are grown to a suitable optical density. In some instances cells are grown to a suitable optical density in an uninduced state, and then an induction signal is applied to commence alkane production.

[00150] Alkanes are produced by the transformed cells. The alkanes generally have 7, 8, 9, 10, 11 or more carbon atoms. In some instances, alkanes are detected. In some instances, alkanes are quantified. In some instances, alkanes are collected.

[00151] In some aspects, a thioesterase such as fatB can be used. To test downstream of fatB, fatty acids of various chain lengths are fed along with inorganic carbon (e.g., C0 ₂ ) to cells, and alkane production is monitored. After fatB addition, cells are provided with inorganic carbon (e.g., C0 ₂ ) and alkane production is monitored. Example 5. Feeding decanoic acid and dodecanoic acid to ai/iit, thioesterase and carB/entD expressing Synechococcus sp. PCC 7002 strain results in detection of corresponding nonane and undecane with secretion.

[00152] Carboxylic acid reductase (carB) (SEQ ID NO. 18) was PCR amplified from Mycobacterium smegmatis and verified by sequencing with multiple primers by Genewiz. Nostoc punctiforme adm, Umbellularia californicia fatB _m (where subscript "m" indicates mature protein, i.e., without leader sequence), and E. coli entD genes were codon-optimized for E. coli overexpression and synthesized by DNA 2.0 (Menlo Park, CA; SEQ ID NOs. 19, 20, and 21). The adm gene was subcloned into a pUC19 vector with a F(cpcB) promoter (US Patent No. 7,794,969), upstream/downstream homology regions, and an erythromycin marker. The resulting plasmid (pAQ4::F(cpcB)-adm _NP u-ermC (SEQ ID NO. 22)) was transformed into wild-type Synechococcus sp. PCC 7002 strain and segregated in the presence of erythromycin (which resulted in strain ADM). The fatB _m , carB, and entD genes were subcloned into a pUC19 vector containing a P(nir07) promoter, upstream/downstream homology regions, and a spectinomycin marker. The resulting plasmid (pAQ3::P(nir07)- fatB _m -carB-entD-SpQcK (SEQ ID NO. 23)) was transformed into the strain ADM and segregated in the presence of the antibiotic spectinomycin.

[00153] The culture of the above final strain was grown in JB3.0 media till OD ₇₃₀ ~ 6 at 37°C, 150 rpm, and with 2% C0 ₂ , in the presence of 15 mM urea. The cells were spun down, resuspended in fresh media without urea, and grown overnight to allow the expression of proteins regulated under the P(nir07) promoter. An overlay of 1.5 mL hexadecane was then added onto the 6 mL culture before 0.1 mM decanoic acid or dodecanoic acid (200 mM stock, dissolved in 100% ethanol) was fed into the culture every 2 hours. At 2 and 4 hours, 0.15 mL of the overlay (triangle) and 0.6 mL of the aqueous culture sample (circle) were collected and analyzed by GC/FID equipped with an hp-5ms column. When fed with decanoic acid, nonane was produced in vivo with an initial rate of > 2.2 mg/L/h, > 90% of which was secreted into the overlay (Figure 7A). When fed with dodecanoic acid, undecane was produced in vivo with an initial rate of 1.2 mg/L/h, ~ 50%> of which was secreted after 4 hours (Figure 7B). This indicates that the undecane product is spontaneously secreted to the overlay outside the cells overtime. Example 6. Biosynthesis of nonane and undecane by Synechococcus sp. PCC 7002 strain expressing adm, thioesterase and carB/entD with secretion.

[00154] Carboxylic acid reductase (carB) (SEQ ID NO. 24) was PCR amplified from Mycobacterium smegmatis and verified by sequencing with multiple primers by Genewiz. Nostoc punctiforme adm, Umbellularia californicia fatB _m (where subscript "m" indicates mature protein, i.e. without leader sequence), Cuphea hookeriana fatB2 _m , and E. coli entD genes were codon-optimized for E. coli overexpression and synthesized by DNA 2.0 (Menlo Park, CA; SEQ ID NOs. 25, 26, 27, and 28). The adm gene was subcloned into a pUC19 vector with V(cpcB) promoter, upstream/downstream homology regions, and an erythromycin marker. The resulting plasmid (pAQ4::F(cpcB)-adm _NP u-ermC (SEQ ID NO. 29)) was transformed into wild-type Synechococcus sp. PCC 7002 strain and segregated in the presence of erythromycin (which resulted in strain ADM). The fatB _m , carB, and entD genes were subcloned into a pUC19 vector containing a P(nir07) promoter, upstream/downstream homology regions, and a spectinomycin marker. The resulting plasmid (pAQ3::P(nir07)- fatB _m -carB-entD-SpecK (SEQ ID NO. 30)) was transformed into the strain ADM and segregated in the presence of the antibiotic spectinomycin, resulting in strain ALK-C 11. The fatB2 _m , carB, and entD genes were subcloned into a pUC19 vector containing a P(nir07) promoter, upstream/downstream homology regions, and a spectinomycin marker. The resulting plasmid (pAQ3 P( r07)-fatB2 _m -carB-entD-SpecR (SEQ ID NO. 31)) was transformed into the strain ADM and segregated in the presence of the antibiotic

spectinomycin, resulting in strain ALK-C9.

[00155] ALK-C9 (Figure 8 A) and ALK-C 11 (Figure 8B) were grown in JB3.0 media till OD730 ~ 3 at 37°C, 150 rpm and with 2% C0 ₂ , in the presence of 15 mM urea. The cells were spun down, resuspended in fresh media without urea and 8 mL hexadecane overlay was then added onto the 32 mL culture. Each day, 0.1 mL of the overlay was collected and analyzed by GC/FID equipped with an hp-5ms column. An increasing amount of nonane was detected in the overlay for ALK-C9 (Figure 9, circle), and an increasing amount of undecane was detected in the overlay for ALK-Cl 1 (Figure 9, triangle). Nonane and undecane are produced continuously by ALK-C9 and ALK-Cl 1 from C0 ₂ .

Example 7: Biosynthesis of tridecane and pentadecane by Synechococcus sp. PCC 7002 strain expressing adm, tesA (thioesterase), and carBlentD.

[00156] Carboxylic acid reductase (carB) (SEQ ID NO. 32) was PCR amplified from Mycobacterium smegmatis and verified by sequencing with multiple primers by Genewiz. Cyanothece sp. ATCC 51142 adm, E. coli tesA _m (where subscript "m" indicates mature protein, i.e. without leader sequence), and E. coli entD genes were codon-optimized for E. coli overexpression and synthesized by DNA 2.0 (Menlo Park, CA; SEQ ID NO. 33 and 34, respectively) with individual ribosome binding sites in front of each gene. All four genes were subcloned into a pUC19 vector containing a P(nir07) promoter, upstream/downstream homology regions, and a spectinomycin marker. The resulting plasmid (pAQ3::P(nir07)-a<im- carB-tesA _m -entD-SpecR (SEQ ID NO. 35)) was transformed into wild-type 7002 strain and segregated in the presence of the antibiotic spectinomycin resulting in strain ALK-C13C15.

[00157] ALK-C13C15 of OD ₇₃₀ ~ 0.5 was grown in a shaker flask at 37°C, 150 rpm with 2% C0 ₂ in the presence of 2 mM urea in JB3.0 medium. After 48 h, 0.5 mL sample of the culture was collected and centrifuged for 5 min at 15,000 rpm. The cell pellet was extracted with acetone and analyzed by GC/FID equipped with an hp-5ms column. Figure 10. A control strain that did not express tesA _m , carB, or entD proteins was treated similarly, and the sample was prepared and analyzed by the same method.

[00158] The growth and alkane production of ALK-C13C15 was also analyzed over a ten day period of time. Figure 1 1 shows the growth curve of ALK-C13C15 over 10 days. Figure 12 shows the production curve of tridecane and pentadecane by ALK-C13C15 over 10 days.

[00159] Nonane and undecane are produced continuously by ALK-C9 and ALK-C 11 from in vivo using C0 ₂ and sunlight.

Example 8: A pathway for the enzymatic synthesis of short-chain alkanes.

[00160] Organisms are constructed which express both adm (alkanal deformylative monooxygenase) and a pathway leading to the formation of a short-chain aldehyde.

Examples of such aldehyde-generating pathways are shown in Table 3.

Table 3: Pathways for production of an aldehyde and subsequent conversion to an alkane/alkene via alkanal deformylative monooxygenase.

[00161] For example, an organism (e.g., cyanobacterium) is engineered according to standard genetic engineering techniques to express Pdc from Zymomonas mobilis (SEQ ID NO: 46) and Adm from N. punctiforme (SEQ ID NO: 36). The Pdc polypeptide converts pyruvate to acetaldehyde. The Adm polypeptide converts acetaldehyde to the short-chain alkane, methane. The genes of the invention may be constructed synthetically or isolated by PCR.

[00162] Alternatively, ketoacid decarboxylase and Adm are recombinantly expressed by the organism. The ketoacid decarboxylase is KivD from Lactococcus lactis subsp. lactis KF147 (SEQ ID NO: 43). Alternatively, the ketoacid decarboxylase is ARO10 from

Saccharomyces cerevisiae S288c (SEQ ID NO: 44).

[00163] The resulting organism comprises an operon coexpressing an adm gene and pdc and/or a 2-ketoacid decarboxylase gene. Cells will be cultured and the presence of the expected product in Table 3 will be measured by gas chromatography analysis.

Example 9: Purified ADM from Nostoc punctiforme PCC 73102 deformylates isovaleraldehyde and forms isobutane in vitro.

[00164] N. punctiforme PCC73102 adm was amplified from the codon-optimized gene obtained from DNA2.0 (Menlo Park, CA; SEQ ID NO. 37) by PCR using primers UN19 (5' - CAT CAC CAC AGC CAG GAT CCG ATG CAG CAA CTG ACC GAT CAA AGC AAA GAA CTG GAC TTC - 3 ^* ) (SEQ ID NO: 40) and UN20 (5 ^* - CGG CCC GCC AAG CTT TTA GGC ACC GAT CAG GCC ATA GGC GCT CAG ACG CAT GAT ATC - 3 ^* ) (SEQ ID NO: 41), allowing the introduction of 5' BamHl and 3' HmdIII restriction sites. The resulting PCR product was inserted into the E. coli vector pCDF-Duetl (Merck; Darmstadt, Germany) by digestion with BamHl and Hindlll and subsequent ligation. The resulting plasmid, pCDF-npu (SEQ ID NO. 42), containing N-terminal His ₆ -tagged N. punctiforme adm, was transformed into E. coli strain BL21(DE3), which was subsequently grown with shaking in Luria-Bertani medium supplemented with 100 μg/mL of spectinomycin in a volume of 1 L to OD ₆ oo = 0.8 before induction with 0.25 mM IPTG for 4 hours in a 2-L shaker flask at 37°C. The ADM protein was purified by affinity chromatography using a Ni- NTA agarose (Qiagen; Valencia, CA) column, eluting the purified protein with a buffer solution of pH 7.5, which contained 100 mM HEPES, 10% glycerol and 250 mM imidazole. An SDS-PAGE gel of the collected fractions is shown in Figure 13. [00165] The activity of the purified ADM was tested on various short-chain aldehydes: isobutyraldehyde, 2-methylbutyraldehyde, and 3-methylbutyraldehyde, among which the 3- methylbutyraldehyde (isovaleraldehyde) is converted to isobutane; whereas the other two showed no detectable deformylation to the corresponding alkane. The activity of purified ADM was also tested on butanal, valeraldehyde, and isovaleraldehyde, as shown in Table 4. The assay conditions were as follows: -0.2 mM N. punctiforme Adm (N-His ₆ -tagged), 0.3 mM l-methoxy-5-methylphenazinium methyl sulfate (Sigma-Aldrich; St. Louis, MO), 10 mM NADH (Sigma-Aldrich), 10 mM aldehyde (stock of 250 mM, dissolved in dimethyl sulfoxide), in a buffer solution containing 100 mM HEPES, 10% glycerol at pH 7.4. Each assay was run at 25°C for 5 minutes, after which it was immediately analyzed by headspace gas chromatography using a 20-m HP-5MS column (Agilent Technologies; Santa Clara, CA). The column was kept at 40°C for 3 min before being heated to 100°C at 15C°/min. Species were identified according to retention time, compared to corresponding standards, which were purchased from Sigma-Aldrich. Results are shown in Table 4. The expression of ADM results in an increase in peak area for each product.

Table 4: Results of chromatagram assays.

Example 10. Biosynthesis of undecane by Synechococcus sp. PCC 7002 strain expressing adm, thioesterase and carB/entD with secretion.

[00166] Carboxylic acid reductase (carB) (SEQ ID NO. 47) was PCR amplified from Mycobacterium smegmatis and verified by sequencing with multiple primers by Genewiz. Hexahistidine-tagged Nostoc punctiforme adm, Umbellularia californicia fatB _m (without leader sequence), and E. coli entD genes were codon-optimized for E. coli overexpression and synthesized by DNA2.0 (Menlo Park, CA; SEQ ID NO. 48, 49, and 50). The adm gene with an N-terminal hexahistidine tag was subcloned into a pUC19 vector with V(cpcB) promoter, upstream and downstream homologous regions, and a erythromycin marker. The resulting plasmid (pAQ4 P(cpcB)-Nhistag_adm(Npu)-ErmC (SEQ ID NO. 51)) was transformed into wild-type Synechococcus sp. PCC 7002 and segregated in the presence of erythromycin (which resulted in strain ADM). The fatB _m , carB and entD genes were subcloned into a pUC19 vector containing a P(nir07) promoter, upstream and downstream homologous regions, and a spectinomycin marker. The resulting plasmid (pAQ3::P(nir07)- fatB _m -carB-entD-SpecK (SEQ ID NO. 52)) was transformed into the strain ADM and segregated in the presence of the antibiotic spectinomycin, resulting in strain JCC6036.

[00167] JCC6036 was grown up in JB3.0 media to OD ₇₃₀ ~ 3 at 37°C, 150 rpm and with 2% CO ₂ , in the presence of 15 mM urea. The cells were spun down, resuspended in fresh JB3.0 media with 3 mM urea and a 6 mL pentadecane overlay was then added onto 30 mL culture. 0.06 mL of the overlay was collected everyday and analyzed by GC/FID equipped with an hp-5ms column. An increased amount of undecane was detected in the overlay for JCC6036 (Figure 14).

Example 11. Feeding decanoic acid to adm and carB/entD-exOressmz Synechococcus sp. PCC 7002 strain results in detection of corresponding nonane with secretion. His-tagged Adm on pAQ3 showed significantly higher activity in vivo.

[00168] Carboxylic acid reductase (carB) (SEQ ID NO. 53) was PCR amplified from Mycobacterium smegmatis and verified by sequencing with multiple primers by Genewiz. Hexahistidine-tagged Nostoc punctiforme adm and E. coli entD genes codon-optimized for E. coli overexpression were synthesized by DNA 2.0 (Menlo Park, CA; SEQ ID NO. 54 and 55). The adm gene was subcloned into a pUC19 vector with F(cpcB) promoter, upstream and downstream homologous regions of pAQ3 or pAQ4, and a spectinomycin marker. The resulting plasmids (pAQ3::P(cpc5)-Nhistag_ai m(N ?w)-SpecR (SEQ ID NO. 56) and pAQ4::P(c/?ci?)-Nhistag_a<im(N/?«)-EmrC (SEQ ID NO. 57)) were transformed into wild- type Synechococcus sp. PCC 7002 strain and segregated in the presence of spectinomycin (resulting in strains ADM3 and ADM4). The carB and entD genes were subcloned into a pUC19 vector containing a P(nir07) promoter, upstream and downstream homologous regions of pAQ7, and a kanamycin marker. The resulting plasmid (pAQ7::P(nir07)-car5- entD-KanR (SEQ ID NO. 58)) was transformed into strains ADM3 and ADM4 and segregated in the presence of the antibiotic spectinomycin (resulting in strains ADM3CARB and ADM4CARB). [00169] The ADM3CARB and ADM4C RB strains were grown in JB3.0 media to OD ₇₃ o ~ 4 at 37°C, 150 rpm and with 2% C0 ₂ , in the presence of 15 mM urea, The cells were spun down, resuspended in fresh JB3.0 media without urea, and grown overnight to allow the expression of proteins regulated by the P(nir07) promoter, 1 ,5 ml pentadecane overlay was then added onto 6 nil, of culture before 4 mM decanoic acid (500 mM. stock, dissol ved in 100% ethanol) was fed into the culture at the beginning, 0.08 mL of the overlay was collected at 1 and 2 hours after feeding and analyzed by GC/F1D equipped with an hp-5ms column.

When fed with decanoic acid, nonane was produced in vivo by the strain ADM3CARB with an initial rate of - 6 mg/L/h (Figure 15).

[00170] A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. All publications, patents and other references mentioned herein are hereby incorporated by reference in their entirety,

TABLE 1

SEQ ID NO DESCRIPTION SEQUENCE

1 aczM {from ATGAATGCAAAACTGAAGAAATTGTTCCAGCAGAAAGTAGACGGCAAGACCATCATCGTG ACCGGTGCAA Ac±n&tobacter GCACCCGTATTGGCTTGACCGTGAGCAAATACCTGGCTCAGGCGGGTGCACACGTGCTGC TGCTGGCGCG

TACGAAAGAGAAACTGGATGAGGTCAAGGCGGAGATTGAAGCGGAAGGCGGTAAGGCTAC TGTTTTCCCG

sp. M-l) , TGCGATTTGAATGACATGG&ATCCATTGACGCAGTCAGC&AAGAGATCCTGG CAGCCGTTGATCATATCG codon- ACATTCTGGTGAATAACGCGGGTCGCAGCATCCGTCGCGCGGTCCACGAAAGCGTGGATC GCTTCCATGA optiiffiized for CTTTGAGCGTACCATGCA CTG&ATTACTTCGGTGCCGTTCGTCTGGTCCTG&ATGTTCTGCCGCACATG E. coli ATGCAGCGCAAAGATGGCCAAATCATTAACATTAGCAGCATTGGCGTTTTGGCGAACGCG ACGCGTTTCA

GCGCGTATGTGGCGAGCAAGGCTGCACTGGATGCCTTCTCCCGTTGTCTGAGCGCCGAGG TCCATTCGCA CAaGATTGCGATTACCTCTATCTATATGCCGCTGGTTCGTACCCCGATGATTGCGCCGAC GAAGATCTAC AAGTATGTCCCAACGTTGTCCCCGGAAGAGGCGGCTGACCTGATTGCTTATGCGATCGTT AAACGTCCGA AAAAGATCGCCACCAATCTGGGTCGCCTGGCAAGCATCACCTACGCGATTGCCCCGGACA TCAACAACAT CCTGATGAGCATCGGCTTTAACCTGTTTCCGTCTAGCACGGCGAGCGTGGGTGAGCAAGA AAAGCTGAAC CTGATTCaACGTGCCTACGCACGTCTGTTTCCTGGTGAACACTGGTAA

2 Plasiaid TGGCGAATGGGACGCGCCCTGTAGCGGCGCATTAAGCGCGGCGGGTGTGGTGGTTACGCG CAGCGTGACC pET28a~acrM GCTACACTTGCCAGCGCCCTAGCGCCCGCTCCTTTCGCTTTCTTCCCTTCCTTTCTCGCC ACGTTCGCCG

GCTTTCCCCGTCAAGCTCTAAATCGGGGGCTCCCTTTAGGGTTCCGATTTAGTGCTTTAC GGCACCTCGA CCCCAAAAAACTTGATTAGGGTGATGGTTCACGTAGTGGGCCATCGCCCTGATAGACGGT TTTTCGCCCT TTGACGTTGGAGTCCACGTTCTTTAATAGTGGACTCTTGTTCCAAACTGGAACAACACTC AACCCTATCT CGGTCTATTCTTTTGATTTATAAGGGATTTTGCCGATTTCGGCCTATTGGTTAAAAAATG AGCTGATTTA ACAAAAATTTAACGCGAATTTTAACAAAATATTAACGTTTACAATTTCAGGTGGCACTTT TCGGGGAAAT GTGCGCGGAACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATG AATTAATTCT TAGAAAAACTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCAGGATTATCAATA CCATATTTTT GAAAAAGCCGTTTCTGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAA GATCCTGGTA TCGGTCTGCGATTCCGACTCGTCCAACaTCAATAC^CCTATTAATTTCCCCTCGTaUiAA ATAAGGTTA TCAAGTGAGAAATCACCATGAGTGACGACTGAATCCGGTGAGAATGGCAAAAGTTTATGC ATTTCTTTCC AGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAAC CGTTATTCAT TCGTGATTGCGCCTGAGCGAGACGAAATACGCGATCGCTGTTAAAAGGACAATTACAAAC AGGAATCGAA TGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATAT TCTTCTAATA CCTGGAATGCTGTTTTCCCGGGGATCGCAGTGGTGAGTAACCATGCATCATCAGGAGTAC GGATAAAATG CTTGATGGTCGGAAGAGGCATAAATTCCGTCAGCCAGTTTAGTCTGACCATCTCATCTGT AACATCATTG GCAACGCTACCTTTGCCATGTTTCAGAAACAACTCTGGCGCATCGGGCTTCCCATACAAT CGATAGATTG TCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATACCCATATAAATCAGCATCCA TGTTGGAATT TAATCGCGGCCTAGAGCAAGACGTTTCCCGTTGAATATGGCTCATAACACCCCTTGTATT ACTGTTTATG TAAGCAGACAGTTTTATTGTTCATGACCAAAATCCCTTAACGTGAGTTTTCGTTCCACTG AGCGTCAGAC CCCGTAGAAAAGATCAAAGGATCTTCTTGAGATCCTTTTTTTCTGCGCGTAATCTGCTGC TTGCAAACAA AAAAACCACCGCTACCAGCGGTGGTTTGTTTGCCGGATCAAGAGCTACCAACTCTTTTTC CGAAGGTAAC TGGCTTCAGCAGAGCGCAGATACCAAATACTGTCCTTCTAGTGTAGCCGTAGTTAGGCCA CCACTTCAAG AACTCTGTAGGACCGCCTACATACCTCGCTCTGCTAATCCTGTTACCAGTGGCTGCTGCC AGTGGCGATA AGTCGTGTCTTACCGGGTTGGACTCAAGACGATAGTTACCGGATAAGGCGCAGCGGTCGG GCTGAACGGG GGGTTCGTGCACACAGCCCAGCTTGGAGCGAACGACCTACACCGAACTGAGATACCTACA GCGTGAGCTA TGAGAAAGCGCCACGCTTCCCGAAGGGAGAAAGGCGGACAGGTATCCGGTAAGCGGCAGG GTCGGAACAG GAGAGCGCACGAGGGAGCTTCCAGGGGGAAACGCCTGGTATCTTTATAGTCCTGTCGGGT TTCGCCACCT CTGACTTGAGCGTCGATTTTTGTGATGCTCGTCAGGGGGGCGGAGCCTATGGA&SA ACGCCAGCSACGCG GCCTTTTTACGGTTCCTGGCCTTTTGCTGGCCTTTTGCTCACATGTTCTTTCCTGCGTTA TCCCCTGATT CTGTGGATAACCGTATTACCGCCTTTGAGTGAGCTGATACCGCTCGCCGCAGCCGA& ;CGACCGAGCGCAG CGAGTCAGTGAGCGAGGAAGCGGAAGAGCGCCTGATGCGGTATTTTCTCCTTACGCATCT GTGCGGTATT TCACACCGCATATATGGTGCACTCTCAGTACAATCTGCTCTGATGCCGCATAGTTAAGCC AGTATACACT CCGCTATCGCTACGTGACTGGGTCATGGCTGCGCCCCGACACCCGCCAACACCCGCTGAC GCGCCCTGAC GGGCTTGTCTGCTCCCGGCATCCGCTTACAGACAAGCTGTGACCGTCTCCGGGAGCTGCA TGTGTCAGAG GTTTTCACCGTCATCACCGAAACGCGCGAGGCAGCTGCGGTAAAGCTCATCAGCGTGGTC GTGAAGCGAT TCACAGATGTCTGCCTGTTCATCCGCGTCCAGCTCGTTGAGTTTCTCCAGAAGCGTTAAT GTCTGGCTTC TGATAAAGCGGGCCATGTTA&GGGCGGTTTTTTCCTGTTTGGTCACTGATGCCTCC GTGTAAGGGGGATT TCTGTTCATGGGGGTAATGATACCGATGAAACGAGAGAGGATGCTCACGATACGGGTTAC TGATGATGAA CATGCCCGGTTACTGGA&CGTTGTGAGGGTA&ACA&CTGGCGGTATGG ATGCGGCGGGACCAGAGAA&AA TCACrCAGGGTCAATGCCAGCGCTTCGTTAATACAGATGTAGGTGTTCCACAGGGTAGCC AGCAGCATCC TGCGATGCAGATCCGGAACATAATGGTGCAGGGCGCTGACTTCCGCGTTTCCAGACTTTA CGAAACACGG AAACCGAAGACCATTCATGTTGTTGCTCAGGTCGCAGACGTTTTGCAGCAGCAGTCGCTT CACGTTCGCT CGCGTATCGGTGATTCATTCTGCTAACCAGTAAGGCAACCCCGCCAGCCTAGCCGGGTCC TCAACGACAG GAGCACGATCATGCGCACCCGTGGGGCCGCCATGCCGGCGATAATGGCCTGCTTCTCGCC GSAACGTTTG GTGGCGGGACCAGTGACGAAGGCTTGAGCGAGGGCGTGCAAGATTCCGAATACCGCAAGC GACAGGCCGA TCATCGTCGCGCTCCAGCGASAGCGGTCCTCGCCGASAATGACCCAGAGCGCTGCCGGCA CCTGTCCTAC GAGTTGCATGATAAAGAAGACAGTCATAAGTGCGGCGACGATAGTCATGCCCCGCGCCCA CCGGAAGGAG CTGACTGGGTTGAAGGCTCTCAAGGGCATCGGTCGAGATCCCGGTGCCTAATGAGTGAGC TAACTTACAT TAATTGCGTTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATT AATGAATCGG CCAACGCGCGGGGAGAGGCGGTTTGCGTATTGGGCGCCAGGGTGGTTTTTCTTTTCACCA GTGAGACGGG CAACAGCTGATTGCCCTTCACCGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCT GGTTTGCC.ee AGCAGGCGAAAATCCTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGTCTTCG GTATCGTCGT ATCCCACTACCGAGATATCCGCACCAACGCGCAGCCCGGACTCGGTSATGGCGCGCATTG CGCCCAGCGC CATCTGATCGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCATTTGCAT GGTTTGTTGA AAACCGGACATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAATTTGATTGCGA GTGAGATATT TATGCCAGCCAGCCAGACGCAGACGCGCCGAGACAGAACTTAATGGGCCCGCTAACAGCG CGATTTGCTG GTGACCCAATGCGACCAGATGCTCCACGCCCAGTCGCGTACCGTCTTCATGGGAGAAAAT AATACTGTTG ATGGGTGTCTGGTCAGAGACATCAAGAAATAACGCCGGAACATTAGTGCAGGCAGCTTCC ACAGCAATGG CATCCTGGTCATCCAGCGGATAGTTAATGATCAGCCCACTGACGCGTTGCGCGAGAAGAT TGTGCACCGC CGCTTTACAGGCTTCGACGCCGCTTCGTTCTACCATCGACACCACCACGCTGGCACCCAG TTGATCGGCG CGAGATTTAATCGCCGCGACAATTTGCGACGGCGCGTGCAGGGCCAGACTGGAGGTGGCA ACGCCAATCA GCAACGACTGTTTGCCCGCCAGTTGTTGTGCCACGCGGTTGGGSATGTAATTCAGCTCCG CCATCGCCGC TTCCACTTTTTCCCGCGTTTTCGCAGAAACGTGGCTGGCCTGGTTCACCACGCGGGAAAC GGTCTGATAA GAGACACCGGCATACTCTGCGACATCGTATAACGTTACTGGTTTCACATTCACCACCCTG AATTGACTCT CTTCCGGGCGCTATCATGCCATACCGCGAAAGGTTTTGCGCCATTCGATGGTGTCCGGGA TCTCGACGCT CTCCCTTATGCGACTCCTGCATTAGGAAGCAGCCCAGTAGTAGGTTGAGGCCGTTGAGCA CCGCCGCCGC AAGGAATGGTGCATGCAAGGAGATGGCGCCCAACAGTCCCCCGGCCACGGGGCCTGCCAC CATACCCACG CCGAAACAAGCGCTCATGAGCCCGAAGTGGCGAGCCCGATCTTCCCCATCGGTGATGTCG GCGATATAGG CGCCAGCAACCGCACCTGTGGCGCCGGTGATGCCGGCCACGATGCGTCCGGCGTAGAGGA TCGAGATCTC GATCCCGCGAAATTAATACGACTCACTATAGGGGAATTGTGAGCGGATAACAATTCCCCT CTAGAAATAA TTTTGTTTAaCTTTAAGAAGGAGATATACCATGGGCAGCAGCCATCATCATCATCATCAC AGCAGCGGCC TGGTGCCGCGCGGCAGCCATATGAATGCAAAACTGAAGAAATTGTTCCAGCAGAAAGTAG ACGGCAAGAC CATCATCGTGACCGGTGCAAGCAGCGGTATTGGCTTGACCGTGAGCAAATACCTGGCTCA GGCGGGTGCA CACGTGCTGCTGCTGGCGCGTACGAAAGAGAAACTGGATGAGGTCAAGGCGGAGATTGAA GCGGAAGGCG GTAAGGCTACTGTTTTCCCGTGCGATTTGAATGACATGGAATCCATTGACGCAGTCAGCA AAGAGATCCT GGCAGCCGTTGATCATATCGACATTCTGGTGAATAACGCGGGTCGCAGCATCCGTCGCGC GGTCCACGAA AGCGTGGATCGCTTCCATGACTTTGAGCGTACCATGCAACTGAATTACTTCGGTGCCGTT CGTCTGGTCC TGAATGTTCTGCCGCACATGATGCAGCGCAAAGATGGCCASATCATTAACATTAGCAGCA TTGGCGTTTT GGCGAACGCGACGCGTTTCAGCGCGTATGTGGCGAGCAAGGCTGCACTGGATGCCTTCTC CCGTTGTCTG AGCGCCGAGGTCCATTCGCACSAGATTGCGATTACCTCTATCTATATGCCGCTGGTTCGT ACCCCGATGA TTGCGCCGACGAAGATCTACAAGTATGTCCCAACGTTGTCCCCGGAAGAGGCGGCTGACC TGATTGCTTA TGCGATCGTTAAACGTCCGAAAAAGATCGCCACCAATCTGGGTCGCCTGGCAAGCATCAC CTACGCGATT GCCCCGGACATCAACAACATCCTGATGAGCATCGGCTTTAACCTGTTTCCGTCTAGCACG GCGAGCGTGG GTGAGCAAGAAAAGCTGAACCTGATTCAACGTGCCTACGCACGTCTGTTTCCTGGTGAAC ACTGGTAAGA ATTCGAGCTCCGTCGACAAGCTTGCGGCCGCACTCGAGCACCACCACCACCACCACTGAG ATCCGGCTGC TAACAAAGCCCGAAAGGAAGCTGAGTTGGCTGCTGCCACCGCTGAGCAATAACTAGCATA ACCCCTTGGG GCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTGSAAGGAGGSACTATATCCGGAT

carboxylic GAGCTCGAGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACC GSAACCGCAC

TCGACGACGAGCAGTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCG CCGCCGCCGC

acid

ACCGTTGCCCGCCGTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCT GCAGACCCTG

reductase TTCACCGGCTACGGTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGAC GAGGGCGGGC amplified GCACCGTGACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGC GCGTGCAAGC fx om GGTCGCCGCGGCCCTGCGCCACSACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGC GACGATCGGT

Mycobacterium TTCGCGAGTCCCGATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGT GTTCCGCTGC

AGCACAACGCACCGGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCC TCACCGTGAG

smegmatis . CGCCGAATACCTCGACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCT CGTGGTGTTC

GACCATCACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGSACAACTC GCCGGCSAGG GCATCGCCGTCACCACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAAC CGATCTACAC CGCCGACCATGATCAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACC CAAGGGTGCG ATGTACACCGAGGCGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCC ACGCCGGTCA TCAACGTCAACTTCATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCG TGCAGAACGG TGGAACCAGTTACTTCGTACCGGSATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCT GGTGCGCCCG ACCGAACTCGGCCTGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACC GTCGACCGCC TGGTCACGCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTG AGCAGGTGCT CGGCGGACGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGC GTTCCTCGAC

TGATCGTGCGGCCACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCT ACTTCAGCACCGA

GAGGTCACCGCGAGCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATG GCCGAGACCGCAC CCGACCACCTGGTGTACGTGGACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGT TCGTGGCGGT

AGGCCGCGCTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCT ACGAGGTGCCGGC CGATTTCATCGTCGAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGG AAAACTGCTG

CCAACCAGTTGCGCGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCC TCACCCAGGCCGC TGCCACGATCCTCGGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGG CGGGGATTCC CTGTCGGCGCTGACACTTTCGAACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTC GGCACCATCG TGAACCCGGCCACCAACCTCGCCCAACTCGCCO.GCACATCGAGGCGCAGCGCACCGCGG GTGACCGCAG GCCGAGTTTCACCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGAC CCTGGACAAG TTCATCGACGCCGAAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCA CGGACGGTGT TGCTCTCGGGCGCO^CGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGiAACGCC TGGCACCTGT CGGCGGCACCCTCATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCT GACCCAGGCC TACGACACCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGG GTGGTCGCCG GTGACATCGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCG AGGTCGACCT GGTGGTGCATCCGGCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCC CAACGTCGTG GGCACGGCCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTG TCCACCGTGT CGGTGGCCA GGGGATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCCGCT

GATCTGTGCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCG CGCTACCGCGGTC AGGTCAACGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCG CGCCGCGGTC GTTCTACATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTT CGTGGCCGAG GCGGTCaCGACGCTCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAAC CCGCACGACG

CTACGACGACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCG CCGCGCACAGACC GTACTGCCGCTGCTGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAA CCCACGGAGG TGTTCCACGCCGCGGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACG AGGCGCTGAT CGACAAGTACATACGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACC

eodon-

GTATTAACGCCATTGTGATCGAAGGCGAGCAAGAAGCATACCAAAACTACCTGGACA TGGCGCAACTGCT

optiitti zed,

GCCGGAGGACGAGGCTGAGCTGATTCGTTTGAGCAAGATGGAGAACCGTCACAAAAAGGG TTTTCAAGCG

Cyanothecs TGCGGCAAGAACCTCAATGTGACTCCGGATATGGATTATGCACAGCAGTTCTTTGCGGAG CTGCACGGCA acta . ATTTTCJ-GAAGGCTAAAGCCGAGGGTAAGATTGTTACCTGCCTGCTCATCCAAAGCCTG ATCATCGAGGC

GTTTGCGATTGCAGCCTACAACATTTACATTCCAGTGGCTGATCCGTTTGCACGTAAAAT CACCGAGGGT GTCGTCAAGGATGAGTATACCCACCTGAATTTCGGCGAAGTTTGGTTGAAGGAACATTTT GAAGCAAGCA

AGCTC

codon- GAGCTCGAGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACC GAAACCGCAC

TCGACGACGAGCAGTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCG CCGCCGCCGC

optimi zed E.

ACCGTTGCCCGCCGTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCT GCAGACCCTG

coll t&sA and

E. coll BntD GCACCGTGACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGC GCGTGCAAGC genes . GGTCGCCGCGGCCCTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGC GACGATCGGT

TTCGCGAGTCCCGATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGT GTTCCGCTGC AGCACAACGCACCGGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCC TCACCGTGAG CGCCGAATACCTCGACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCT CGTGGTGTTC GACCATCACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTC GCCGGCAAGG GCATCGCCGTCACCACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAAC CGATCTACAC CGCCGACCATGATCAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACC CAAGGGTGCG ATGTACACCGAGGCGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCC ACGCCGGTCA

TGGAACCAGTTACTTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGC GCTGGTGCGCCCG

TGGTCACGCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGC GTGAGCAGGTGCT CGGCGGACGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGC GTTCCTCGAC ATCACCCTGGGCGCACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACA CGCGACGGTG TGATCGTGCGGCCACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACT TCAGCACCGA CAAGCCCTACCCGCGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTA CAAGCGCCCC GAGGTCACCGCGAGCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCC GAGACCGCAC CCGACCACCTGGTGTACGTGGACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGT TCGTGGCGGT CGCCAACCTGGAGGCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGG CAACAGCGAG

AGGCCGCGCTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCT ACGAGGTGCCGGC CGATTTCaTCGTCGAGACCGAGCCGTTO-GCGCCGCCAACGGGCTGCTGTCGGGTGTCGG AAAACTGCTG CGGCCCAACCTCAAAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCG GCCACGCAGG CCAACCAGTTGCGCGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCA CCCAGGCCGC

TGAACCCGGCCACCAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCG CGGGTGACCGCAG GCCGAGTTTCACCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGAC CCTGGACAAG TTCATCGACGCCGAAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCA CGGACGGTGT TGCTCTCGGGCGCCAACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCC TGGCACCTGT CGGCGGCACCCTCATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCT GACCCAGGCC TACGACACCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGG GTGGTCGCCG GTGACATCGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCG AGGTCGACCT GGTGGTGCATCCGGCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCC CAACGTCGTG GGCACGGCCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTG TCCACCGTGT CGGTGGCCATGGGGATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGG TGCGCCCGCT CGACGGCGGATACGCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCG GGAGGCCCAC GATCTGTGCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGC TACCGCGGTC AGGTCAACGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCG CGCCGCGGTC GTTCTACATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTT CGTGGCCGAG GCGGTCACGACGCTCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAAC CCGCACGACG ACGGGATCTCCCTGGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACC GGGTCGACGA CTACGACGACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCG CGCACAGACC GTACTGCCGCTGCTGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAA CCCACGGAGG TGTTCCACGCCGCGGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACG AGGCGCTGAT CGACAAGTACATACGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCAGGAGGTTTTT ACAATGGCTG ATACTTTGTTGATTTTGGGTGATTCTCTCTCTGCAGGCTACCGTATGTCCGCGAGCGCGG CATGGCCGGC TCTGCTGAaCGATAAGTGGCAGAGCAAGACCAGCGTGGTCAATGCGAGCATCAGCGGCGA TACCAGCCAG CAGGGTCTGGCACGTCTGCCAGCGCTGCTGAAGCAACACCAGCCGCGTTGGGTGCTGGTT GAACTGGGCG GCAaTGACGGTCTGCGTGGTTTTCAGCCGCAGCAGACCGAACAAACGTTGCGTCAGATTC TGCAGGACGT CAAGGCGGCTAACGCGGAACCGCTGCTGATGCAAATTCGCCTGCCGGCGAATTATGGTCG TCGTTACAAC GAGGCTTT LAGCGCCATTTATCCTAAACTGGCTAAAGAGTTTGACGTGCCGCTGCTGCCGTTCTTCAT GG AAGAGGTCTACCTGAAACCGCAATGGATGCAAGACGACGGTATTCATCCGAATCGTGATG CACAACCTTT CATCGCGGATTGGATGGCGAAGCAATTGCAACCGCTGGTGAACCATGACTCGTAAAAGCT TGTTGCTGCA TGCAGGAGGTTTTTACAATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCACACGT TACATTTCGT CGAATTTGATCCGGCGAACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCA GCTGCAGCAC GCAGGCCGTAAGCGTAAAACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTG CGCGAGTACG GCTACAAATGCGTGCCGGCCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGAAGTTT ACGGTTCCAT CTCCCACTGCGGTACTACCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATAT TGAAGAGATA

TrcrCTGTCCAGACGGCACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAG CGTCTGGCGG ACTGTGGTCTGGCGTTCAGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGT TCAAGGCTTC CGAGATCCAAACCGATGCGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACA GGTTATCATT CACCGTGAGAATGAGATGTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACC CTGTGCCAGC ACGACTGAGAATTC

plasmid AAAAGCAGAGCATTACGCTGACTTGACGGGACGGCGCAAGCTCATGACCAAAATCCCTTA ACGTGAGTTA pAQ3 : : Pnir07

TCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATCAA

adm carB tesA GAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACT GTTCTTCTAG entD SpecR, TGTAGCCGTAGTTAGCCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC TGCTAATCCT

GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG GATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACA CCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAA CGCCTGGTAT CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCG TCAGGGGGGC GGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGC CTTTTGCTCA CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTG AGCTGATACC GCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCATCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT GTTGTAAAACGACGGCCAGTCTTAAGCTCGGGCCCCCTGGGCGGTTCTGATAACGAGTAA TCGTTAATCC

AATATTTAaGGGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTTATAA ATGAGAAAAAAGC AACGCACTTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTATAATTAAACTAT TCATCTATTA TTTATGATTTTTTGTATATACAATATTTCTAGTTTGTTAAAGAGAATTAAGAAAATAAAT CTCGAAAATA ATAAAGGGAAAATCAGTTTTTGATATCAAAATTATACATGTCAACGATAATACAAAATAT AATACAAACT ATAAGATGTTATCAGTATTTATTATGCATTTAGAATAAATTTTGTGTCGCCCTTCGCTGA ACCTGCAGGC GAGCATTTCAACGATGATGAATGGGACGGCGAACCCACTGAACCCGTCGCCATTGACCCA GAACCGCGCA AAGAACGGGAAAAAATTGATCTCGATCTGGAGGATGAACCAGAGGAAAACCGCAAACCGC AAAAAATCAA AGTGAAGTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTCAAACCACAACTTTTTG GGATGCTGAT GGTAAACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG AAGCCGAACTACGCACCATCTGGGGGAAACCCGATACCCGTAAATCGTTCCTGACCGGAC TCGCGGAAAA AGGCTACGGTGACACCCAACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAAGTGA TGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC TGATTTTCTCGAAGTACACCGGAAAGCAGCAAGAATTTTTAGATTTTGTCCTAGACCAAT ACATTCGAGA AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCAAAC CGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG ATGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCTTG TAGCAATTGC TACTAAAAACTGCGATCGCTGCTGAAATGAGCTGGAATTTTGTCCCTCTCAGCTCAAAAA GTATCAATGA TTACTTAATGTTTGTTCTGCGCAAACTTCTTGCAGAACATGCATGATTTACAAAAAGTTG TAGTTTCTGT TACCAATTGCGAATCGAGAACTGCCTAATCTGCCGAGTATGCGATCCTTTAGCAGGAGGA AAACCATATG CAAGAACTGGCCCTGAGAAGCGAGCTGGACTTCAATAGCGAAACCTATAAAGATGCGTAT AGCCGTATTA ACGCCATTGTGATCGAAGGCGAGCAAGAAGCATACCAAAACTACCTGGACATGGCGCAAC TGCTGCCGGA GGACGAGGCTGAGCTGATTCGTTTGAGCAAGATGGAGAACCGTCACAAAAAGGGTTTTCA AGCGTGCGGC AAGAACCTCAATGTGACTCCGGATATGGATTATGCACAGCAGTTCTTTGCGGAGCTGCAC GGCAATTTTC AGAAGGCTAAAGCCGAGGGTAAGATTGTTACCTGCCTGCTCATCCAAAGCCTGATCATCG AGGCGTTTGC AGTTGGAGGACGCCA¾C&A¾GAG&ACTTACCGCTGGTCTGGCAGATGTTG A¾CCAGGTCGA¾A¾GGATGC

^TCTGGTGGAGGACTTTATGIRTTAGCTATGGTGAGGCACTGAGC RGAGAAATCATGAAGATGAGCGCGTACGGTCTGCGTGCAGCATAAGAGCTCG AGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCG CACTCGACGA CGAGC^TCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCC GCACCGTTG CCCGCCGTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACC CTGTTCACCG GCTACGGTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCG GGCGCACCGT GACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCA AGCGGTCGCC GCGGCCCTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATC GGTTTCGCGA

CGCACCGGRAAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCAC CGTGAGCGCCGAA TACCTCGACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTG TTCGACCATC ACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCA AGGGCATCGC CGTCACCAC∞TGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCT ACACCGCCGAC

:TCGGGTTCCACCGGCGCACCCAAGGGTGCGATGTACA :TGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCAACGT CAACTTCATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAA CGGTGGAACC AGTTACTTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGC CCGACCGAAC TCGGCCTGGT CCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGGTCAC GCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGT GCTCGGCGGA CGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTC GACATCACCC TGGGCGCACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACG GTGTGATCGT

CCGCGAGCGTCTTCGiACCGGGiACGGCTACTACCACACCGGCGACGTCATGGCCGA GACCGCACCCGACCA CCTGGTGTACKTGGACCGTCGCAAC^CGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCG GTCGCCaAC CTGGAGGCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGC GAGCGCAGTT TCCTTCTGG∞GTGGTGGTCCCGACGCCGGAGGCGCTCGAGC^TACGATCCGGCCGCGC TCAAGGCCGC GCTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCC GGCCGATTTC ATCGTCGAGACCGAGCCGTTO.GCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTG CTGCGGCCCA ACCTCAAAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGC AGGCCAACCA GTTGCGCGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGC CGCTGCCACG ATCCTCGGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGAT TCCCTGTCGG CGCTGACLACTTTCGAACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACC ATCGTGAACCC GGCCACCAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCG CAGGCCGAGT TTCaCCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGAC AAGTTCATCG ACGCCGAAAC^TCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGGT GTTGCTCTC GGGCGCCJ-ACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCAC CTGTCGGCGGC

CCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGG TCGCCGGTGACAT CGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGA CCTGGTGGTG CATCCGGCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTC GTGGGCACGG CCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTGTCCACCG TGTCGGTGGC

GGATACGCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAG GCCCACGATCTGT GCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCG GTCAGGTCAA CGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCG GTCGTTCTAC ATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCC GAGGCGGTCA CGACGCTCGGC.GCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCAC GACGACGGGAT CTCCCTGGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGA CGACTACGAC GACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAG ACCGTACTGC

CGCCGCGGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGC GCTGATCGACAAG

AACGATAAGTGGCAGAGCAAGACCAGCGTGGTCAATGCGAGCATCAGCGGCGATACC AGCCAGCAGGGTC TGGCACGTCTGCCAGCGCTGCTGAAGCAACACCAGCCGCGTTGGGTGCTGGTTGAACTGG GCGGCAATGA CGGTCTGCGTGGTTTTCAGCCGCAGCAGACCGAACAAACGTTGCGTCAGATTCTGCAGGA CGTCAAGGCG GCTAACGCGGAACCGCTGCTGATGCftAATTCGCCTGCCGGCGAATTATGGTCGTCGTTA CAACGAGGCTT TC -GCGCCaT TATCCTAAACTGGCTAAAGAGTTTGACGTGCCGCTGCTGCCGTTCTTCATGGAAGAGGT CTACCTGAAACCGCAATGGATGCAAGACGACGGTATTCATCCGAATCGTGATGCACAACC TTTCATCGCG GATTGGATGGCGAAGCAATTGCAACCGCTGGTGAACCATGACTCGTAAAAGCTTGTTGCT GCATGCAGGA GGTTTTTACAATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCACACGTTACATTT CGTCGAATTT GATCCGGCGAACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAG CACGC-feGGCC GTAAGCGTAAAACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGT ACGGCTACAA ATGCGTGCCGGCCATTGGTGAACTGCGTOU CCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCAC TGCGGTACTACCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATATTGAAGAG ATATTCTCTG TCCAGACGGCACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAGCGTCTGG CGGACTGTGG TCTGGCGTTCAGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGC TTCCGAGATC CAAACCGATGCGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACAGGTTATC ATTCACCGTG AGAATGAGATGTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACCCTGTGCC AGCACGACTG AGAATTCGGTTTTCCGTCCTGTCTTGATTTTCAAGCAAACAATGCCTCCGATTTCTAATC GGAGGCATTT GTTTTTGTTTATTGCAAAAACAAAAAATATTGTTACAAATTTTTACAGGCTATTAAGCCT ACCGTCATAA ATAATTTGCCaTTTACTAGTTTTTAATTAACC^AACCTTGACCGAACGCAGCGGTGGTAA CGGCGCAGT GGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGGGGTACAGTCTATGCCTCGGGCATC CAAGCAGCAA GCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCAACGATGTTACGCAGCAG GGCAGTCGCC CTAAAACAAAGTTAAACATCATGAGGGAAGCGGTGATCGCCGAAGm^

TGGCGTCATCGAGCGCCATCTCGAACCGACGTTGCTGGCCGTACATTTGTACGGCTCCGC AGTGGATGGC GGCCTGAAGCCACACAGTGATATTGATTTGCTGGTT&CGGTG&CCGTAAGGC TTGATG¾AAC¾ACGCGGC GAGCTTTGATCAACGACCTTTTGGAAACTTCGGCTTCCCCTGGAGAGAGCGAGATTCTCC GCGCTGTAGA AGTCACCATTGTTGTGCACGACGACATCATTCCGTGGCGTTATCCAGCTAAGCGCGAACT GCAATTTGGA GAaTGGCAGCGCAATGACATTCTTGCAGGTATCTTCGAGCCAGCCACGATCGACATTGAT CTGGCTATCT TGCTGACAAAAGCAAGAGAACATAGCGTTGCCTTGGTAGGTCCAGCGGCGGAGGAACTCT TTGATCCGGT TCCTGAACAGGATCTATTTGAGGCGCT&AATGAAACCTT&ACGCTATGG&am p;ACTCGCCGCCCGACTGGGCT GGCGATGAGCGAAATGTAGTGCTTACGTTGTCCCGCATTTGGTACAGCGCAGTAACCGGC AAAATCGCGC CGAAGGATGTCGCTGCCGACTGGGCAATGGAGCGCCTGCCGGCCCAGTATCAGCCCGTCA TACTTGAAGC TAGACAGGCTTATCTTGGACAAGAAGAAGATCGCTTGGCCTCGCGCGCAGATCAGTTGGA AGAATTTGTC CACTACGTGAAAGGCGAGATCACCAAGGTAGTCGGCAAATAATGTCTAACAATTCGTTCA AGCCGACGCC GCTTCGCGGCGCGGCTTAACTCAAGCGTTAGATGCACTAAGCACATAATTGCTCACAGCC AAACTATCAG GTCAAGTCTGCTTTTATTATTTTTAAGCGTGCATAATAAGCCCTACACAAATTGGGAGAT ATATCATGAG GCGCGCCACGAGAAAGAGTTATGACAAATTAAAATTCTGACTCTTAGATTATTTCCAGAG AGGCTGATTT TCCCAATCTTTGGGAAAGCCTAAGTTTTTAGATTCTATTTCTGGATACATCTCAAAAGTT CTTTTTAAAT GCTGTGCAAAATTATGCTCTGGTTTAATTCTGTCTAAGAGATACTGAATACAACATAAGC CAGTGAAAAT TTTACGGCTGTTTCTTTGATTAATATCCTCCAATACTTCTCTAGAGAGCCATTTTCCTTT TAACCTATCA GGCAATTTAGGTGATTCTCCTAGCTGTATATTCCAGAGCCTTGAATGATGAGCGCAAATA TTTCTAATAT GCGACAaAGACCGTAACCAAGATATAAAAAACTTGTTAGGTAATTGGAAATGAGTATGTA TTTTTTGTCG TGTCTTAGATGGTAATAAATTTGTGTACATTCTAGATAACTGCCCAAAGGCGATTATCTC CAAAGCCATA TATGACGGCGGTAGTAGAGGATTTGTGTACTTGTTTCGATAATGCCCGATAAATTCTTCT ACTTTTTTAG ATTGGCAATATTGAGTAATCGAATCGATTAATTCTTGATGCTTCCCAGTGTCATAAAATA AACTTTTATT CAGATACCAATGAGGATCATAATCATGGGAGTAGTGATAAATCATTTGAGTTCTGACTGC TACTTCTATC GACTCCGTAGCATTAAAAATAAGCATTCTCAAGGATTTATCAAACTTGTATAGATTTGGC CGGCCCGTCA AAAGGGCGACACCCCATAATTAGCCCGGGCGAAAGGCCCAGTCTTTCGACTGAGCCTTTC GTTTTATTTG ATGCCTGGCAGTTCCCTACTCTCGCATGGGGAGTCCCCACACTACCATCGGCGCTACGGC GTTTCACTTC TGAGTTCGGCATGGGGTCAGGTGGGACCACCGCGCTACTGCCGCCAGGCAAACAAGGGGT GTTATGAGCC ATATTCAGGTATAAATGGGCTCGCGATAATGTTCAGAATTGGTTAATTGGTTGTAACACT GACCCCTATT TGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAA ATGCTTCAAT AATATTGAaAAAGGAAGAATATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTT TTGCGGCATT TTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCA GTTGGGTGCA CGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCC GAAGAACGTT TTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACG CCGGGCAAGA GCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCAC AGAAAAGCAT CTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAAC ACTGCGGCCA ACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGG GGGATCATGT AACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGA CACCACGATG CCTGTAGCGATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCT TCCCGGCAAC

A&TTA&TAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTC GGCCCTTCCGGCTGGCTG GTTTATTGCTGATAAATCCGGAGCCGGTGAGCGTGGTTCTCGCGGTATCATCGCAGCGCT GGGGCCAGAT GGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAA CGAAATAGAC AGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGT

GGTACCAGGAGGTTTTTACATGGACCGTAAAAGCAAGCGTCCGGACATGCTGGTTGA TTCCTTTGGTCTG

optimized GAAAGCACCGTGCAGGACGGTCTGGTTTTCCGTCAGTCTTTCTCCATTCGTAGCTATGAG ATTGGTACTG

ATCGTACCGCCTCTATCGAAACCCTGATGAATCACCTGCAAGAAACCTCTCTGAACCATT GTAAGTCTAC

Cuphea TGGCATCCTGCTGGACGGTTTCGGTCGTACCCTGGAGATGTGCAAACGCGACCTGATTTG GGTAGTGATC hookeziana AaAaTGCAGATCAAAGTTAACCGTTATCCGGCATGGGGTGATACCGTTGAAATCAACACC CGCTTTTCTC leaderless GTCTGGGCAAAATCGGTATGGGCCGTGACTGGCTGATCTCTGACTGTAACACTGGTGAAA TTCTGGTTCG fatB2 gene. TGCTACTAGCGCATACGCGATGATGAACCAGAAAACCCGTCGCCTGAGCAAGCTGCCGTA CGAGGTCCAC

CAGGAGATTGTTCCGCTGTTTGTAGACAGCCCAGTGATTGAGGATTCTGACCTGAAAGTG CATAAATTCA AAGTGAAGACCGGTGACAGCATCCAAAAAGGCCTGACCCCAGGTTGGAACGATCTGGACG TTAACCAGCA CGTTTCCAaCGTGAAGTATATCGGTTGGATTCTGGAGAGCATGCCGACCGAGGTCCTGGA AACCCAGGAG CTGTGTTCCCTGGCGCTGGAGTACCGCCGTGAGTGCGGCCGTGACAGCGTGCTGGAGTCT GTGACCGCTA TGGACCCAAGCAAAGTTGGTGTTCGTAGCCAGTACCAGCACCTGCTGCGTCTGGAAGACG GTACTGCTAT CGTGAACGGTGCAACTGAATGGCGTCCTAAAAACGCGGGTGCAAACGGTGCTATCAGCAC CGGTAAAACC TCTAACGGTAACTCCGTGAGCTAAAAGCTT

plasisid AAAAGCAGAGCATTACGCTGACTTGACGGGACGGCGCAAGCTCATGACCAAAATCCCTTA ACGTGAGTTA pAQ3: :P(nir07

5 TCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATCAA adm C S fa. GAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACT GTTCTTCTAG tB2 @ntD Spec TGTAGCCGTAGTTAGCCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC TGCTAATCCT R. GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG

GATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACA CCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAA CGCCTGGTAT CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCG TCAGGGGGGC

CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGA GTGAGCTGATACC GCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCATCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT GTTGTAAAACGACGGCCAGTCTTAAGCTCGGGCCCCCTGGGCGGTTCTGATAACGAGTAA TCGTTAATCC GCAAaTAACGTAAAAACCCGCTTCGGCGGGTTTTTTTATGGGGGGAGTTTAGGGAAAGAG CATTTGTCAG AATATTTAAGGGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTTATAAATG AGAAAAAAGC AACGCACTTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTATAATTAAACTAT TCATCTATTA TTTATGATTTTTTGTATATACA¾TATTTCTAGTTTGTT&A¾GAG&ATT&a mp;AGA¾A¾T&A¾TCTCG&A¾ATA ATAAAGGGA¾AATCAGTTTTTGATATC¾A&ATT&T&C&TGTC AACGATAAT&C¾A&ATATAAT&C¾AACT ATAAGATGTTATC&GTATTTATT&TGC&TTT&G&ATA&am p;ATTTTGTGTCGCCCTTCGCTG&ACCTGCAGGC GAGCATTTCAACGATG&TG.½TGGGACGGCG.½CCC&CTG¾ACCCGTCG CCATTGACCCAGAACCGCGCA J¾AGAACGGGASA¾A¾TTG&TCTCG&TCTGG&GGATG&ACC &G&GGA¾A¾CCGCA¾ACCGC&A¾A¾ATC&A AGTGAAGTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTCAAACCACAACTTTTTG GGATGCTGAT GGTAaACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG AAGCCGAACTACGCACCATCTGGGGGAAACCCGATACCCGTAAATCGTTCCTGACCGGAC TCGCGGAAAA AGGCTACGGTGACACCC&ACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAA GTGATGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC

AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCA AACCGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG ATGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCTTG TAGCAATTGC TACTAAAAACTGCGATCGCTGCTGAAATGAGCTGGAATTTTGTCCCTCTCAGCTCAAAAA GTATCAATGA TTACTTAaTGTTTGTTCTGCGCAAACTTCTTGCAGAACATGCATGATTTACAAAAAGTTG TAGTTTCTGT TACCAATTGCGAATCGAGAACTGCCTAATCTGCCGAGTATGCGATCCTTTAGCAGGAGGA AAACCATATG CA&GAACTGGCCCTGAGAAGCGAGCTGGACTTCAATAGCG&AACCTAT& ;AAGATGCGTATAGCCGTATTA ACGCCATTGTGATCGAAGGCGAGCAAGAAGCATACCAAAACTACCTGGACATGGCGCAAC TGCTGCCGGA GGACGAGGCTGAGCTGATTCGTTTGAGCAAGATGGAG&ACCGTCACAAAAAGGGTT TTC&AGCGTGCGGC AAGAaCCTCAATGTGACTCCGGATATGGATTATGCACAGCAGTTCTTTGCGGAGCTGCAC GGCAATTTTC AGAAGGCrAAAGCCGAGGGTAAGATTGTTACCTGCCTGCTCATCCAAAGCCTGATCATCG AGGCGTTTGC GATTGCAGCCTACAACATTTACATTCCAGTGGCTGATCCGTTTGCACGTAAAATCACCGA GGGTGTCGTC AAGGATGAGTATACCCACCTGAATTTCGGCGAAGTTTGGTTGAAGGAACATTTTGAAGCA AGCAAGGCGG AGTTGGAGGACGCC&ACAAAGAGAACTTACCGCTGGTCTGGCAGATGTTG&A CCAGGTCG&AAAGGATGC CGAAGTGCTGGGTATGGAGAAAGAGGCTCTGGTGGAGGACTTTATGATTAGCTATGGTGA GGCACTGAGC

A&CATCGGCTTTTCTACGAGAGAAATCATGAAGATGAGCGCGTACGGTCTGCG TGCAGCAT&AGAGCTCG AGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCG CACTCGACGA CGAGCAGTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGC CGCACCGTTG CCCGCCGTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACC CTGTTCACCG GCTACGGTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCG GGCGCACCGT GACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCA AGCGGTCGCC GCGGCCCTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATC GGTTTCGCGA GTCCCGATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGC TGCAGCACAA CGCACCGGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGT GAGCGCCGAA TACCTCGACCTCGCAGTCGAATCCGTGCGGGACGTC&ACTCGGTGTCGCAGCTCGT GGTGTTCGACCATC ACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCA AGGGCATCGC CGTCACCACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTA CACCGCCGAC CATGATCAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGT GCGATGTACA CCGAGGCGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGG TCATCAACGT CAACTTCATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAA CGGTGGAACC AGTTACTTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGC CCGACCGAAC TCGGCCTGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACC GCCTGGTCAC GCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGT GCTCGGCGGA CGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTC GACATCACCC TGGGCGCACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACG GTGTGATCGT GCGGCCACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCAC CGACAAGCCC TACCCGCGTGGCG&ACTGCTGGTCAGGTCGC&AACGCTGACTCCCGGGTACT ACAAGCGCCCCGAGGTCA CCGCGAGCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCG CACCCGACCA CCTGGTGTACGTGGACCGTCGC&ACAACGTCCTC&AACTCGCGCAGGGCGAG TTCGTGGCGGTCGCCAAC CTGGAGGCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGC GAGCGCAGTT

rCCTTCTGGCCGTGGTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCG CGCTCAAGGCCGC GCTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCC GGCCGATTTC

ArCGTCGAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAA CTGCTGCGGCCCA ACCTCAAaGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGC AGGCCAACCA GTTGCGCGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGC CGCTGCCACG ATCCTCGGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGAT TCCCTGTCGG CGCTGACACTTTCGAACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCA TCGTGAACCC GGCCACCAACCTCGCCC&ACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTG ACCGCAGGCCGAGT TTCACCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGAC AAGTTCATCG ACGCCGAAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGG TGTTGCTCTC GGGCGCCAACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACC TGTCGGCGGC ACCCTCATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAG GCCTACGACA CCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCG CCGGTGACAT CGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGA CCTGGTGGTG CATCCGGCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTC GTGGGCACGG CCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTGTCCACCG TGTCGGTGGC CATGGGGATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCC GCTCGACGGC GGATACGCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCC CACGATCTGT GCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCG GTCAGGTCAA CGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCG GTCGTTCTAC ATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCC GAGGCGGTCA CGACGCTCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACG ACGACGGGAT CTCCCTGGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGA CGACTACGAC GACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAG ACCGTACTGC CGCTGCTGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGG AGGTGTTCCA CGCCGCGGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCT GATCGACAAG TACATACGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCAGGAGGTTTTTACATGGA CCGT&A&AGC A&GCGTCCGGACATGCTGGTTGATTCCTTTGGTCTGG¾J^GCACCGTGC&G GACGGTCTGGTTTTCCGTC AGTCTTTCTCCATTCGTAGCTATGAGATTGGTACTGATCGTACCGCCTCTATCGAAACCC TGATGAATCA

CCTGCA&GAAACCTCTCTGAACCATTGT&AGTCTACTGGCATCCTGCTG GACGGTTTCGGTCGTACCCTG

GAGATGTGCAAACGCGACCTGATTTGGGTAGTGATCAAAATGCAGATCAAAGTTAAC CGTTATCCGGCAT GGGGTGATACCGTTGAAATCAACACCCGCTTTTCTCGTCTGGGCAAAATCGGTATGGGCC GTGACTGGCT GATCTCTGACTGTAACACTGGTGAAATTCTGGTTCGTGCTACTAGCGCATACGCGATGAT GAACCAGAAA ACCCGTCGCCTGAGCAAGCTGCCGTACGAGGTCCACCAGGAGATTGTTCCGCTGTTTGTA GACAGCCCAG TGATTGAGGATTCTGACCTGAAAGTGCATAAATTCAAAGTGAAGACCGGTGACAGCATCC AAAAAGGCCT GACCCCAGGTTGGAACGATCTGGACGTTAACCAGCACGTTTCCAACGTGAAGTATATCGG TTGGATTCTG GAGAGCATGCCGACCGAGGTCCTGGAAACCCAGGAGCTGTGTTCCCTGGCGCTGGAGTAC CGCCGTGAGT GCGGCCGTGACAGCGTGCTGGAGTCTGTGACCGCTATGGACCCAAGCAAAGTTGGTGTTC GTAGCCAGTA CCAGCACCTGCTGCGTCTGGAAGACGGTACTGCTATCGTGAACGGTGCAACTGAATGGCG TCCTAAAAAC GCGGGTGCAAACGGTGCTATCAGCACCGGTAAAACCTCTAACGGTAACTCCGTGAGCTAA AAGCTTGTTG CTGCATGCAGGAGGTTTTTACAATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCA CACGTTACAT TTCGTCGAATTTGATCCGGCGAACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTAT GCCCAGCTGC AGCACGCAGGCCGTAAGCGTAAAACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATG CCCTGCGCGA GTACGGCTACAAATGCGTGCCGGCCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGA AGTTTACGGT TCCATCTCCCACTGCGGTACTACCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATT GATATTGAAG AGATATTCTCTGTCCAGACGGCACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGC ACGAGCGTCT GGCGGACTGTGGTCTGGCGTTCAGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAG CGCGTTCAAG GCTTCCGAGATCCAAACCGATGCGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAG CAACAGGTTA TCATTCACCGTGAGAATGAGATGTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTA TCACCCTGTG CCAGCACGACTGAGAATTCGGTTTTCCGTCCTGTCTTGATTTTCAAGCAAACAATGCCTC CGATTTCTAA TCGGAGGCATTTGTTTTTGTTTATTGCAAAAACAAAAAATATTGTTACAAATTTTTACAG GCTATTAAGC CTACCGTCATAAATAATTTGCCATTTACTAGTTTTTAATTAACCAGAACCTTGACCGAAC GCAGCGGTGG TAACGGCGCAGTGGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGGGGTACAGTCTAT GCCTCGGGCA TCCAaGCAGCAAGCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCAACGAT GTTACGCAGC AGGGCAGrCGCCCTAAAACAAAGTTAAACATCATGAGGGAAGCGGTGATCGCCGAAGTAT CGACTCAACT ATCAGAGGTAGTTGGCGTCATCGAGCGCCATCTCGAACCGACGTTGCTGGCCGTACATTT GTACGGCTCC GCAGTGGATGGCGGCCTGAAGCCACACAGTGATATTGATTTGCTGGTTACGGTGACCGTA AGGCTTGATG AAaCAACGCGGCGAGCTTTGATCAACGACCTTTTGGAAACTTCGGCTTCCCCTGGAGAGA GCGAGATTCT CCGCGCTGTAGAAGTCACCATTGTTGTGCACGACGACATCATTCCGTGGCGTTATCCAGC TAAGCGCGAA CTGCAATTTGGAGAATGGCAGCGCAATGACATTCTTGCAGGTATCTTCGAGCCAGCCACG ATCGACATTG ATCTGGCTATCTTGCTGACAAAAGCAAGAGAACATAGCGTTGCCTTGGTAGGTCCAGCGG CGGAGGAACT CTTTGATCCGGTTCCTGAACAGGATCTATTTGAGGCGCTAAATGAAACCTTAACGCTATG GAACTCGCCG CCCGACTGGGCTGGCGATGAGCGAAATGTAGTGCTTACGTTGTCCCGCATTTGGTACAGC GCAGTAACCG GCAAAATCGCGCCGAAGGATGTCGCTGCCGACTGGGCAATGGAGCGCCTGCCGGCCCAGT ATCAGCCCGT CATACTTGAAGCTAGACAGGCTTATCTTGGACAAGAAGAAGATCGCTTGGCCTCGCGCGC AGATCAGTTG GAAGAATrTGTCCACTACGTGAAAGGCGAGATCACCAAGGTAGTCGGCAAATAATGTCTA ACAATTCGTT CAAGCCGACGCCGCTTCGCGGCGCGGCTTAACTCAAGCGTTAGATGCACTAAGCACATAA TTGCTCACAG CCAAACTATCAGGTCAAGTCTGCTTTTATTATTTTTAAGCGTGCATAATAAGCCCTACAC AAATTGGGAG ATATATCATGAGGCGCGCCACGAGAAAGAGTTATGACAAATTAAAATTCTGACTCTTAGA TTATTTCCAG AGAGGCTGATTTTCCCAATCTTTGGGAAAGCCTAAGTTTTTAGATTCTATTTCTGGATAC ATCTCAAAAG TTCTTTTTAAATGCTGTGCAAAATTATGCTCTGGTTTAATTCTGTCTAAGAGATACTGAA TACAACATAA GCCAGTGAaAATTTTACGGCTGTTTCTTTGATTAATATCCTCCAATACTTCTCTAGAGAG CCATTTTCCT TTTAACCTArCAGGCAATTTAGGTGATTCTCCTAGCTGTATATTCCAGAGCCTTGAATGA TGAGCGCAAA TATTTCTAATATGCGACAAAGACCGTAACCAAGATATAAAAAACTTGTTAGGTAATTGGA AATGAGTATG TATTTTTTGTCGTGTCTTAGATGGTAATAAATTTGTGTACATTCTAGATAACTGCCCAAA GGCGATTATC TCCAAAGCCATATATGACGGCGGTAGTAGAGGATTTGTGTACTTGTTTCGATAATGCCCG ATAAATTCTT CTACTTTTTTAGATTGGCAATATTGAGTAATCGAATCGATTAATTCTTGATGCTTCCCAG TGTCATAAAA TAAACTTTTATTCAGATACCAATGAGGATCATAATCATGGGAGTAGTGATAAATCATTTG AGTTCTGACT GCTACTTCTATCGACTCCGTAGCATTAAAAATAAGCATTCTCAAGGATTTATCAAACTTG TATAGATTTG GCCGGCCCGTCAAAAGGGCGACACCCCATAATTAGCCCGGGCGAAAGGCCCAGTCTTTCG ACTGAGCCTT TCGTTTTATTTGATGCCTGGCAGTTCCCTACTCTCGCATGGGGAGTCCCCACACTACCAT CGGCGCTACG GCGTTTCACTTCTGAGTTCGGCATGGGGTCAGGTGGGACCACCGCGCTACTGCCGCCAGG CAAACAAGGG GTGTTATGAGCCATATTCAGGTATAAATGGGCTCGCGATAATGTTCAGAATTGGTTAATT GGTTGTAACA CTGACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAA TAACCCTGAT AAATGCTTCAATAATATTGAAAAAGGAAGAATATGAGTATTCAACATTTCCGTGTCGCCC TTATTCCCTT TTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGA TGCTGAAGAT CAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAG AGTTTTCGCC CCGAAGAaCGTTTTCCAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTAT CCCGTATTGA CGCCGGGCAAGAGCAACTCGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTA CTCACCAGTC ACAGAAAAGCATCTTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACC ATGAGTGATA

GGGGGATCATGTAACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACC AAACGACGAGCGT GACACCACGATGCCTGTAGCGATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTA CTTACTCTAG CTTCCCGGCAACAATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGC GCTCGGCCCT TCCGGCTGGCTGGTTTATTGCTGATAAATCCGGAGCCGGTGAGCGTGGTTCTCGCGGTAT CATCGCAGCG CTGGGGCCAGATGGTAAGCCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCA ACTATGGATG AACGAAaTAGACAGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGT carB MTSDVHDATDGV ETALDDEQSTRRIAELYATDPEFAAAAPLPAVV AAHKPGLRLAEILQTLFTGYGDR

Mycobacterium PALGY aREMTDEGGKTV KLLPKFDTLTYAQWSKVQAVAAALRHNFAQPIYPGDAVATIGFASPDYL

TLDLVCAYLGLVSVPLQKNAPVSRIAPIIAEVEPRILTVSAEYLDIAVES¾∞)VNSV SQLWF HKPEV smegmatis DHRDAIAR&REQIAGKGIAV TLDAIADEGAGLPAEPIYTADHDQRI^ILYTSGSTGAPKGA YTEAW

ARLWTMSFITGDPTPVIf3Vf3FMPLNHLGGRIPISTAVQNGGTSYFVPESDMSTLFEDL ALVRPTELGLVP RVM)MLYQHHLA VDRLVTQGADELT&E Q&G&ELREQVLGGRVITGFVSTAPL&AEMR¾FLDITLGAHI VDGYGLTETGAV EDGVIVEPPVIDYKLIDVPELGYFSTDKPYPRGELLVRSQTLTPGYYKEPEV ASVF DRDGYYHTGDVMAET&PDHLVYVDRRNf3VLKLAQGEFVAVAf3LEAVFSG& ALVRQIFVYGNSERSFLLAV VVPTPEM.EQYDPA&LKAAIoMSLQRTAEDAELQSYEVP )FIVETEPFS¾&NGLLSGVGKLLRPNLKDR YGQRLEQMYADI&ATQ&NQLRELRRA&ATQPVIDTLTQ&A& ;TILGTGSEV¾SDAHFTDLGGDSLSALTLS NLLSDFFGFEVPVGTIVNPATNLAQLAQKIEAQRTAGDRRPSFTTVKGADATEIRASELT LDKFIDAETL RMPGLP VTTEPRTWJLSGANGWIJGRFLTLQWICERLAPVGGTLITITOGRDDAAARARLTQAYDT DPEL SRRFAELADRHLRVVAGDIGDPNLGLTPEIWHRIjy^VDLWHPAALWKVLPYRQLFGPWV GTAEVIK L .TERIKPVTYLSWSVaMGIPDE¾EDGDIEWSPVEPLDGGYANGYGNSKWAGEVLLEEAK DLCGLPV ATFRSDMILAHPRYRGQVNVPDMFTRLLLSLLITGVAPRSFYIGDGERPRAHYPGLTVDF VAEAVTTLGA QQREGWSYDV NPKDDGISLDVW m,IRAGKPIDEVDDYDD»WREE¾TALT.½PEKERAQTVLPLLKA FRAPQAPLRGAPEPTEVFHAAVRTAKVGPGDIPHLDEALIDKYIRDLREFGLI

entD E.coli TTHTSLPFAGKTLHrraroPANFCEQDLL»¾PKYAQLQKAGRKRKTEHLAGRIAAVYA LREYGYKCVP

AIGELRQPVWPAEVYGSISHCGTTALAWSRQPIGIDIEEIFSVQTARELTDNIITPAEHE RMDCGLAF SLALTLAFSAKESAFKASEIQTDAGFLD Q11S5S3KQQVIIERENE FAVKWQIKEKIVITLCQKD acrM MHAKLK LFQQ TOG TIIVTGASSGIGLTVS YLAQAGA!OT _^

Acinetobacter CDLNDMESIDAVS EIIjyiV HIDILVffliAGRSIRRAVHESV RFHDFERT QLNYFGAVRLVLWLPK

MQR DGQIINISSIGVLANATRFSAYVASK^ALDAFSRCLSAEVHSKKIAITSIYMPLVRTP IAPTKIY sp. M-l YVPTLSPEEAADLIAYAIVKRPK IATf3LGRLASITYAIAPDIf3NILMSIGFNLFPSSTASVGEQEKLN

LIQRAYARLFPGEKW

fadB E.coli MK VWLMYPADVPTEINPDRYQSLVDMFEQSVARYADQPAFVNMGEVM FR LEERSRAFAAYLQQGLG

L KGDRVALMPNLLQYPVALFGILRAG IVVWNPLYTPRELEKQLNIISGASAIVIVSNFAKTLEKVVD KTAVQWIL R GDQLSTA GTV¾FV^¾YI! ILVP YHLPDAISFRSALHNGYR QYV PELVPEDIJ¾F LQYRGGTTGVAKG.¾^TKRM4LANLEQWATYGPLLHPGKELWTALPLYHIFALTI13CL LFIELGGQNL LITHPRDIPGLV EIJ¾ YPFTAITGWTLFNALL™ EFQQLDFSSLHLSAGGG PVQQWAERWV LTG QYLLEGYGLTECAPLVSVNPYDIDYHSGSIGLPVPSTEA LVDDDDNEVPPGQPGELCV GPQVMLGYWQ RPDATDEIIKNGM,KTGDIAV DEEGFLRIV RKKD ILVSGFIWYPNEIEDVV QKPGVQEVAAVGVPS GSSGEAVKIFW KDPSLTEESLVTFCRRQLTGYIWPKLVEFRDELPKSNVG ILRRELRDEARGKVDFSK

A

fatB (C12 MATTSLASAFCSM AVMLARDGRGM PRSSDLQLRAGNAPTSL If3GTKFSYTESLKRLPDWSMLFAVI fatty acid) TTIFSAAEKQWT13LEW PKPKLPQLLDDKFGLKGLVFRRTFAIRSYEVGPDRSTSILAVM13H QEATL13H

AKSVGILGDGFGTTLE S RDI^^^^RT!WAVERYPTWGDTVEVECWIGASGOTG RRDFLVRDC TGE Uia ellularia ILTRCrSLSVI^TRTRRLSTIPDEVRGEIGPAFIDWA DDEIK LQKLiroSTADYIQGGLTPRWiroL californica DWQHVIOTLKWAWFETVPDSIFESKHISSFTLEYRRECTRDSWJRSLTTVSGGSSEAGLV CDKLLQLE

GGSEVLRARTEWRPKLTDSFRGISVIPAEPRV

fatBma (fatB MEW PKPKLPQLLDDKFGLKGLVFRRTFAIRSYEVGPDRSTSILAV NH QEATLNHAKSVGILGDGFGT without TLEMSKRDL </RRTHVAVERYPTWGDTVEVEC¾IGASGNF3GMRRDFLVRDC TGEILTRCTSLSVLMF3

TRTRRLSTIPDEVRGEIGPAFIDWAVKDDEIKKLQKLMSTADYIQGGLTPRWNDLDVNQH VJFFLLKYVA

leader WFETVPDSIFESHHISSFTLEYRRECTRDSVLRSLTTVSGGSSEAGLVCDHLLQLEGGSE VLRARTEWR sequence) P LTDSFRGISVIPAEPRV

XJrabellularia

californica

fatB2 (C8 CIO MVAAAASSAFFPVPAPGASPKPG FGNWPSSLSPSFKPKSIPNGGFQV ANDSAHPKANGSAVSL SGSL fatty acid) NTQEDTSSSPPPRTFLHQLPDWSRLLTAITWFV S RPD KDR S RPD LV SFGLESTVQDGLVFRQ

SFSIRSYEIGTDRTASlETLMNKLQETSLNKC STGILLDGFGRTLE C RDLIWWIKMQI VTTOYPAW Cuphea GDTVEINTRFSRLGKIG GRDWLISDCNTGEILVRATSAYAE^MQ TRRLS LPYEVHQEIVPLFV SPV hooker ana IEDSDL ¥H FKVKTGDSIQKGLTPGWM)LDWQKVSWKYIGWILES PTEVLETQELCSIiALEYRREC

GRDSVLESVTAMDPSKVGVRSQYQHLLRLEDGTAIVf3GATE¾RPKNAGANGAISTG TSNGNSVS fatB2iaat (fatB DR S RPDMLVDSFGLESTVQDGLVFRQSFSIRSYEIGTDRTASIETL NHLQETSLNHCKSTGILLDG

2 without FGRTLEMCKRDLIWVI QIKVNRYPAWGDTVEINTRFSRLGKIGMGRDWLISDCfSTGEILVRATSAYA f®^QKTRRLSKLPYEVHQEIVPLFVDSPVIEDSDLKVHKFKV TGDSIQ GLTPGWffi)LDWQHVSiiV Y leader IGWILESMP EWJETQELCSLALEYRRECGRDSWJES^AMDPS VGTOSQYQKLLRLEDGTAI NGATE sejuexice) WRPKNAGANGAISTGKTSNGNSVS

Cuphea

hookeriana

kivd MYWGDYLLDRIJiELGIEEIFGVPGDYNLQFLDQIISR DM WVGNANELNASY ¾DGYART AAAFLT

Lac ococcus TFGVGELSAVNGIAGSYAENLPVVEIVGSPTSKVQNEGKFVHKTIJUSGDFKHFMKi^EP V AARTLLTAE mTYEIDRW,SALL ER P\^INLP\^A¾AA!i¾E PSLPL ENPTSOTSDQEILN IQESL NA PIV 1 c 3 ITGHEIISFGLEf3TV QFIS T LPITTLNFG SSVDETLPSFLGIYNGKLSEPf3LKEFVESADFILMLG

V LTDSSTGAFTHKLNENK ISLNIDEGKIFNESIQNF FESLISSLLDLSGIEYKGKYIDKKQEDFVPS

i3ALLSQDRLWQAVENLTQSf3ETIVAEQGTSFFGASSIFL P SHFIGQPL¾GSIGYTFPAALGSQIADKE SRHLLFIGDGSLQLTVQELGLAIREKINPICFIINTOGYTVEREIHGPNQSYNIilPMWN YSKLPESFGAT EERVVS IVRTEfffiFVSVM EAQADPfSRMYWIELVLAKEDAPKV'LKKMGKLFAEQN S

carboxylic ATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCGACGACGAG CAGTCGACCC acid GCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACCGTTGCCCG CCGTGGTCGA

CGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTCACCGGCTA CGGTGACCGC

reductase aiapi fied CCGGCGCTGGGATACCGCGCCCGTGA¾CTGGCCACCGACGAGGGCGGGCGCACCGTGAC GCGTCTGCTGC from CGCGGTTCGAC&CCCTC&CCT&CGCCC&GGTGTGG ^, rCGCGCGTGC¾AGCGG ^, rCGCCGCGGCCC ^, rGCGCC&

CA¾CTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTTCGCGAGTC CCGATTACCTG

Mycobacterivim ACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGCAGCAC&A CGCACCGGTCAGCC smsgsi&tis . GGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGCCGAATACC TCGACCTCGC

AGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGACCATCACCC CGAGGTCGAC GACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCATCGCCGTC ACCACCCTGG ACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTACACCGCCGACCATG ATCAGCGCCT CGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATGTACACCGA GGCGATGGTG GCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCAACGTCAAC TTCATGCCGC TCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGGAACCAGTT ACTTCGTACC GGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACCGAACTCGG CCTGGTTCCG CGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGGTCACGCAG GGCGCCGACG AACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGGCGGACGCG TGATCACCGG ATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTCGACATCACCCTGGG CGCACACATC GTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGATCGTGCGG CCACCGGTGA TCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCACCGACAAGCCCTACC CGCGTGGCGA ACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGCCCCGAGGTCACCGC GAGCGTCTTC GACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCGACCACCTG GTGTACGTGG ACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGCCAACCTGG AGGCGGTGTT CTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGCGAGCGCAGTTTCCT TCTGGCCGTG GTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAGGCCGCGCTG GCCGACTCGC TGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCCGGCCGATTTCATCG TCGAGACCGA GCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTGCTGCGGCCCAACCT CAAAGACCGC TACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGCAGGCCAACCAGTTG CGCGAACTGC GGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGCCGCTGCCACGATCC TCGGCACCGG GAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGATTCCCTGTCGGCGCT GACACTTTCG AACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGAACCCGGCC ACCAACCTCG CCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCCGAGTTTCA CCACCGTGCA CGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGACAAGTTCATCGACGC CGAAACGCTC CGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGGTGTTGCTCTCGGGC GCCAACGGCT GGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGGCGGCACCC TCATCACGAT CGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTACGACACCGA TCCCGAGTTG TCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTGACATCGGC GACCCGAATC TGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGACCTGGTGGTGCATC CGGCAGCGCT GGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTCGTGGGCACGGCCGA GGTGATCAAG CTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTGTCCACCGTGTCGGTGGCCATG GGGATCCCCG ACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCCGCTCGACGGCGGAT ACGCCAACGG CTACGGCAaCAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCCCACGATCTGTGCGG GCTGCCCGTG GCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCGGTCAGGTCAACGTG CCAGACATGT TCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCGGTCGTTCTACATCG GAGACGGTGA GCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCGGTCACGAC GCTCGGCGCG CAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACGGGATCTCC CTGGATGTGT TCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTACGACGACT GGGTGCGTCG GTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAGACCGTACTGCCGCT GCTGCACGCG TTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGGAGGTGTTCCACGCC GCGGTGCGCA CCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCTGATCGACAAGTACA TACGCGATCT GCGTGAGTTCGGTCTGATCTGA

codon- ATGCAGCAACTGACCGATCAAAGCAAAGAACTGGACTTCAAGAGCGAGACGTACAAAGAC GCCTATAGCC optiiftizsd. GCATTAACGCGATCGTCATTGAAGGCGAACAAGAGGCGCATGAAAACTACATCACCCTGG CGCAGCTGCT

GCCTGAGAGCCACGACGAACTGATTCGCCTGAGCAAAATGGAGAGCCGTCACAAGAAAGG TTTTGAGGCG

Nostoe TGTGGCCGCAATCTGGCGGTGACCCCGGACCTGCAATTTGCGAAGGAGTTCTTTAGCGGT CTGCACCAGA pimct±£orm& ATTTCCAGACGGCCGCAGCCGAGGGCAAAGTCGTCACTTGTTTGTTGATCCAGAGCCTGA TTATTGAATG acfci. CTTTGCTATTGCGGCGTACAACATTTACATTCCGGTCGCCGATGACTTTGCGCGTAAAAT CACGGAAGGT

GTTGTCAAaGAGGAGTATTCCCACCTGAATTTCGGTGAAGTGTGGTTGAAGGAACATTTT GCGGAATCTA AAGCCGAATTGGAACTGGCAAATCGCCAGAACCTGCCGATCGTTTGGAAGATGCTGAACC AAGTGGAAGG TGATGCACATACGATGGCGATGGAGAAGGACGCATTGGTTGAGGACTTTATGATTCAGTA TGGCGAAGCA CTGTCCAATATCGGTTTCAGCACCCGTGATATCATGCGTCTGAGCGCCTATGGCCTGATC GGTGCCTAA

eodon- ATGGAGTGGAAACCAAAACCGAAACTGCCTCAGCTGCTGGATGACCACTTCGGTCTGCAC GGCCTGGTTT optiittized, TCCGTCGTACCTTCGCTATCCGTTCTTACGAAGTCGGCCCTGATCGCTCCACCTCCATCC TGGCGGTAAT

GAACCACATGCAGGAAGCAACTCTGAACCATGCGAAAAGCGTAGGTATCCTGGGCGATGG TTTCGGCACT

Umbellularla ACTCTGGAGATGTCCAAACGTGATCTGATGTGGGTTGTTCGCCGTACCCATGTCGCGGTT GAACGCTACC californicla CGACCTGGGGCGATACGGTTGAAGTGGAATGCTGGATCGGCGCGTCCGGCAACAACGGCA TGCGTCGCGA fatS _m (without TTTCCTGGTTCGCGATTGTAAGACGGGCGAGATTCTGACCCGTTGCACGTCCCTGAGCGT TCTGATGAAT

ACCCGTACCCGTCGTCTGAGCACCATCCCGGACGAAGTTCGCGGTGAAATTGGCCCGGCA TTCATCGATA ACGTTGCAGTAAAAGACGATGAAATCAAGAAACTGCAGAAACTGAATGACTCTACCGCGG ACTACATCCA

sequence) . GGGTGGTCTGACCCCGCGCTGGAACGACCTGGACGTGAACCAGCACGTCAACAACCTGAA ATACGTAGCT

TGGGTATTCGAAACGGTCCCGGATTCTATCTTCGAATCTCACCACATCAGCTCCTTCACC CTGGAATACC GTCGTGAGTGTACCCGTGACTCCGTTCTGCGCTCTCTGACCACGGTATCCGGCGGTAGCT CTGAAGCCGG TCTGGTTTGCGATCACCTGCTGCAGCTGGAAGGCGGCAGCGAGGTTCTGCGTGCTCGTAC TGAGTGGCGT CCGAaGCTGACTGACTCTTTCCGCGGCATCTCTGTTATCCCGGCAGAGCCTCGTGTGTAA cod.on~ ATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCACACGTTACATTTCGTCGAATTT GATCCGGCGA optimized E, ACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCC GTAAGCGTAA coll ntD. ftACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCTAC& amp;AATGCGTGCCG GCCATTGGTGAACTGCGTC¾ACCGGTTTGGCCGGC&G¾AGTTT&CGGTTC C&TCTCCCACTGCGGTACT& CCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTG TCCAGACGGC ACGCGAGCTGACGG&CaACATC&TTACCCCGGCAGAGC&CGAGCGTCT GGCGGACTGTGGTCTGGCGTTC AGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATC CAAACCGATG CGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTG AGAATGAGAT GTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACCCTGTGCCAGCACGACTG A

plasitti d TAGAAAAACTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCAGGATTATCAATA CCATATTTTT pAQ : : P { cpcB) GAaAaAGCCGTTTCTGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAA GATCCTGGTA

TCGGTCTGCGATTCCGACTCGTCCAACATCAATACAACCTATTAATTTCCCCTCGTCAAA AATAAGGTTA

-ermC. TCA&GTGAGJLAATCACC&TGAGTGACG&CTG&ATCCGGTGAGA ATGGCAAAAGTTTATGCATTTCTTTCC

AGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAAC CGTTATTCAT TCGTGATTGCGCCTGAGCGAGGCGAAATACGCGATCGCTGTTAAAAGGACAATTACAAAC AGGAATCGAG TGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATAT TCTTCTAATA

CTTGATGGTCGGAAGTGGCATAAATTCCGTCAGCCAGTTTAGTCTGACCATCTCATC TGTAACATCATTG GCAACGCTACCTTTGCCATGTTTCAGAAACAACTCTGGCGCATCGGGCTTCCCATACAAG CGATAGATTG TCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATACCCATAT&AATCAGCA TCCATGTTGGAATT TAATCGCGGCCTCGACGTTTCCCGTTGAATATGGCTCATATTCTTCCTTTTTCAATATTA TTGAAGCATT TATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAA ATAGGGGTCA GTGTTACAACCAATTAACCAATTCTGAACATTATCGCGAGCCCATTTATACCTGAATATG GCTCATAACA CCCCTTGTTTGCCTGGCGGCAGTAGCGCGGTGGTCCCACCTGACCCCATGCCGAACTCAG AAGTGAAACG CCGTAGCGCCGATGGTAGTGTGGGGACTCCCCATGCGAGAGTAGGGAACTGCCAGGCATC AAATAAAACG AAAGGCTCAGTCGAAAGACTGGGCCTTTCGCCCGGGCTAATTAGGGGGTGTCGCCCTTTA CACGTACTTA GTCGCTGAAGGCCTCACTGGCCCCTGCAGGGATGGTGGAATGCTGGTTATCTGGTGGGGA TTAAGTGGTG TTTTACTAAAGCTTGAACAACTCAAGAAAGATTATATTCGCAATAACTGCCAATAATCCC AGCATCTTGA GAAAATCCAGCAAACCGGGGGCAAAACACCAGCAAGAAGCCAGCAGACTATCACCAAATC CCCAGCGTAC AGCTAGAAATAACTGAGCAGTTGTATTCAATTACCTTCTGGTCAAGCCGAGGAAATTTCC CCACACCTTA TACACCrcrGGAAGGTTTTTTTGACGAAGCGCAAAATATCCACAATCGGCTGGGGACTTC TTCTGTCAGA AAaTGGCAGAAATTTTTGAATGTGTTGGCGATCGCCCTCATCAATGATTATTAGAGAACT TTTGTCCCTG ArGTTGGGAATACTCTTGATGACAATTGTGATTGCTCAAAGAAGAAAGAAATTTGGAGTA AATCTCTAAA AGGGGACTGAAATATTTGTATGGTCAGCATGACCACTGAAATGGAGAGAAGTCTAAGACA GTAGATGTCT TAGATATAAGCCTCATTAGAAGCCATGCCATAAAACAGATTTTGTGGATGAAACAACTTG AAATAGTTCA GTTGTAGACCATGTTATAAACATTTATTCTTAACACAGTGACACATTAATGACTCATATA TCCGTCCAAA AAAAACTAAAATGTTTGTAAATTTAGTTTTGCGGCCGCGTCGACTTCGTTATAAAATAAA CTTAACAAAT CTATACCCACCTGTAGAGAAGAGTCCCTGAATATCAAAATGGTGGGATAAAAAGCTCAAA AAGGAAAGTA GGCTGTGGTTCCCTAGGCAACAGTCTTCCCTACCCCACTGGAAACTAAAAAAACGAGAAA AGTTCGCACC GAACATCAATTGCATAATTTTAGCCCTAAAACATAAGCTGAACGAAACTGGTTGTCTTCC CTTCCCAATC CAGGACAaTCTGAGAATCCCCTGCAACATTACTTAACAAAAAAGCAGGAATAAAATTAAC AAGATGTAAC AGACATAAGTCCCATCACCGTTGTATAAAGTTAACTGTGGGATTGCAAAAGCATTCAAGC CTAGGCGCTG AGCTGTTTGAGCATCCCGGTGGCCCTTGTCGCTGCCTCCGTGTTTCTCCCTGGATTTATT TAGGTAATAT CTCTCATAAATCCCCGGGTAGTTAACGAAAGTTAATGGAGATCAGTAACAATAACTCTAG GGTCATTACT TTGGACTCCCTCAGTTTATCCGGGGGAATTGTGTTTAAGAAAATCCCAACTCATAAAGTC AAGTAGGAGA TTAATCATATGCAGCAACTGACCGATCAAAGCAAAGAACTGGACTTCAAGAGCGAGACGT ACAAAGACGC

CrATAGCCGCATTAACGCGATCGTCATTGAAGGCGAACAAGAGGCGCATGAAAACTACAT CACCCTGGCG CAGCTGCTGCCTGAGAGCCACGACGAACTGATTCGCCTGAGCAAAATGGAGAGCCGTCAC AAGAAAGGTT TTGAGGCGTGTGGCCGCAATCTGGCGGTGACCCCGGACCTGCAATTTGCGAAGGAGTTCT TTAGCGGTCT GCACCAGAaTTTCCAGACGGCCGCAGCCGAGGGCAAAGTCGTCACTTGTTTGTTGATCCA GAGCCTGATT ATTGAATGCTTTGCTATTGCGGCGTACAACATTTACATTCCGGTCGCCGATGACTTTGCG CGTAAAATCA CGGAAGGTGTTGTCAAAGAGGAGTATTCCCACCTGAATTTCGGTGAAGTGTGGTTGAAGG AACATTTTGC GGAATCTAAAGCCGAATTGGAACTGGCAAATCGCCAGAACCTGCCGATCGTTTGGAAGAT GCTGAACCAA GTGGAAGGTGATGCACATACGATGGCGATGGAGAAGGACGCATTGGTTGAGGACTTTATG ATTCAGTATG GCGAAGCACTGTCCAATATCGGTTTCAGCACCCGTGATATCATGCGTCTGAGCGCCTATG GCCTGATCGG TGCCTAACrCGAGCAATTCGGTTTTCCGTCCTGTCTTGATTTTCAAGCAAACAATGCCTC CGATTTCTAA TCGGAGGCATTTGTTTTTGTTTATTGCAAAAACAAAAAATATTGTTACAAATTTTTACAG GCTATTAAGC

CrACCGTCATAAATAATTTGCCATTTACTAGTTTTAATTAACGTGCTATAATTATACTAA TTTTATAAGG AGGAAAAAATATGGGCATTTTTAGTATTTTTGTAATCAGCACAGTTCATTATCAACCAAA CAAAAAATAA GTGGTTATAATGAATCGTTAATAAGCAAAATTCATATAACCAAATTAAAGAGGGTTATAA TGAACGAGAA AAATATAAAACACAGTCAAAACTTTATTACTTCAAAACATAATATAGATAAAATAATGAC AAATATAAGA TTAaATGAACATGATAATATCTTTGAAATCGGCTCAGGAAAAGGCCATTTTACCCTTGAA TTAGTAAAGA GGTGTAATTTCGTAACTGCCATTGAAATAGACCATAAATTATGCAAAACTACAGAAAATA AACTTGTTGA TCACGATAaTTTCCAAGTTTTAAACAAGGATATATTGCAGTTTAAATTTCCTAAAAACCA ATCCTATAAA ATATATGGTAATATACCTTATAACATAAGTACGGATATAATACGCAAAATTGTTTTTGAT AGTATAGCTA ATGAGATTTATTTAATCGTGGAATACGGGTTTGCTAAAAGATTATTAAATACAAAACGCT CATTGGCATT ACTTTTAATGGCAGAAGTTGATATTTCTATATTAAGTATGGTTCCAAGAGAATATTTTCA TCCTAAACCT AAAGTGAATAGCTCACTTATCAGATTAAGTAGAAAAAAATCAAGAATATCACACAAAGAT AAACAAAAGT ATAATTATTTCGTTATGAAATGGGTTAACAAAGAATACAAGAAAATATTTACAAAAAATC AATTTAACAA TTCCTTAAAACATGCAGGAATTGACGATTTAAACAATATTAGCTTTGAACAATTCTTATC TCTTTTCAAT AGCTATAAaTTATTTAATAAGTAAGTTAAGGGATGCATAAACTGCATCCCTTAACTTGTT TTTCGTGTGC CTATTTTTTGTGGCGCGCCCAGTTTCCTTTACTGGCCCTAAAGTCGCTGTGGCTAGGGTT CCGAAGGGGC ATTATTGGCTCGCGGCTTTACAACCTTGATAAGGAGAGAGATGACAGTTTTTTTTCTCTT TTGCTTAGTA AAACAGCAAATTTAAGGCATGTTAAAGAGCAGTAGAACGAAATGGTTGAGCCGGCCTCGA TACACTCAAT TAACTACTAATAGCTTCAATAAATTTTGGGACGATTGAAGCTATTTTTTTGAAAATCAAC TCTTAATATC TCCTGTCTCAAAAGAGTTAATTGCTAAACAAAAGCCAGTTTCAGCGAAAAATCTAGAGTT TTATAGGTTC GTTCTCAGTACAGGACAAAAAGTTTGAAAAGGATAGAGGGAGAGGGTTTGATGGAAATAA GCACAAATCA ATCAaGCCCTCATGAATCAGATTAGCGAAATTCGCCGCCAATTGCGACCTCATCTCGGAT GGCATGGAGC CAGACTGTCATTTATCGCCCTCTTCCTGGTGGCACTGTTCCGAGCAAAAACCGTCAATCT CGCCAAACTC GCCACCGTCTGGGGAGGCAATGCAGCAGAAGAGTCTAATTACAAACGCATGCAGCGATTC TTTCAGTCCT TTGACGTCAACATGGACAAAATCGCCAGGATGGTAATGAATATCGCGGCTATCCCGCAAC CTTGGGTCTT AAGCATCGACCGCACCAACGGCCGGCCTACATGGCCCGTCAATCGAAGGGCGACACAAAA TTTATTCTAA ATGCATAATAAATACTGATAACATCTTATAGTTTGTATTATATTTTGTATTATCGTTGAC ATGTATAATT TTGATATCAAAAACTGATTTTCCCTTTATTATTTTCGAGATTTATTTTCTTAATTCTCTT TAACAAACTA GAaATATTGTATATACAAAAAATCATAAATAATAGATGAATAGTTTAATTATAGGTGTTC ATCAATCGAA AAAGCAACGrATCTTATTTAAAGTGCGTTGCTTTTTTCTCATTTATAAGGTTAAATAATT CTCATATATC AAGCAAAGTGACAGGCGCCCTTAAATATTCTGACAAATGCTCTTTCCCTAAACTCCCCCC ATAAAAAAAC CCGCCGAAGCGGGTTTTTACGTTATTTGCGGATTAACGATTACTCGTTATCAGAACCGCC CAGGGGGC.ee GAGCTTAAGACTGGCCGTCGTTTTACAACACAGAAAGAGTTTGTAGAAACGCAAAAAGGC CATCCGTCAG GGGCCTTCTGCTTAGTTTGATGCCTGGCAGTTCCCTACTCTCGCCTTCCGCTTCCTCGCT CACTGACTCG CTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGG TTATCCACAG AATCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACC GTAAAAAGGC CGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACG CTCAAGTCAG AGGTGGCGASACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGGAAGCTCCCTC GTGCGCTCTC CTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGG CGCTTTCTCA TAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGT GCACGAACCC CCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTA AGACACGACT TATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTG CTACAGAGTT CTTGAAGTGGTGGGCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCT GCTGAAGCCA GTTACCTTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGC GGTGGTTTTT TTGTTTGCAaGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCT TTTCTACGGG GTCTGACGCTCAGTGGAACGACGCGCGCGTAACTCACGTTAAGGGATTTTGGTCATGAGC TTGCGCCGTC. CCGTCAAGTCAGCGT&ATGCTCTGCTTT

plasisi l AAAAGCAGAGCATTACGCTGACTTGACGGGACGGCGCAAGCTCATGACCAAAATCCCTTA ACGTGAGTTA pAQ3 : : P (nir07

TCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATCAA GAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACT GTTCTTCTAG

entD-SpecR. TGTAGCCGTAGTTAGCCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC TGCTAATCCT

GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG GATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACA CCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAA CGCCTGGTAT CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCG TCAGGGGGGC

CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGA GTGAGCTGATACC. GCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCATCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT GTTGTAAAACGACGGCCAGTCTTAAGCTCGGGCCCCCTGGGCGGTTCTGATAACGAGTAA TCGTTAATCC GCAAATAACGTAAAAACCCGCTTCGGCGGGTTTTTTTATGGGGGGAGTTTAGGGAAAGAG CATTTGTCAG AATATTTAAGGGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTTATAAATG AGAAAAAAGC AACGCACTTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTATAATTAAACTAT TCATCTATTA TTTATGATTTTTTGTATATACAATATTTCTAGTTTGTTAAAGAGAATTAAGAAAATAAAT CTCGAAAATA ATAAAGGGAA&ATCAGTTTTTGATATCAAAATTATACATGTCAACGATAATACAAA ATATAATACAAACT ATAaGATGTTATCAGTATTTATTATGCATTTAGAATAAATTTTGTGTCGCCCTTCGCTGA ACCTGCAGGC GAGCATTTCAACGATGATGAATGGGACGGCGAACCCACTGAACCCGTCGCCATTGACCCA GAACCGCGCA AAGAACGGGAAAAAATTGATCTCGATCTGGAGGATGAACCAGAGGAAAACCGCAAACCGC AAAAAATCAA AGTGAAGTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTCAAACCACAACTTTTTG GGATGCTGAT GGTAAACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG AAGCCGAACTACGCACCATCTGGGGGAAACCCGATACCCGTAAATCGTTCCTGACCGGAC TCGCGGAAAA AGGCTACGGTGACACCCAACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAAGTGA TGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC

AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCA AACCGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG ATGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCTTG TAGCAATTGC TACTAAAAACTGCGATCGCTGCTGAAATGAGCTGGAATTTTGTCCCTCTCAGCTCAAAAA GTATCAATGA TTACTTAATGTTTGTTCTGCGCAAACTTCTTGCAGAACATGCATGATTTACAAAAAGTTG TAGTTTCTGT TACCAATTGCGAATCGAGAACTGCCTAATCTGCCGAGTATGCGATCCTTTAGCAGGAGGA AAACCATATG GAGTGGAAACCAAAACCGAAACTGCCTCAGCTGCTGGATGACCACTTCGGTCTGCACGGC CTGGTTTTCC GTCGTACCTTCGCTATCCGTTCTTACGAAGTCGGCCCTGATCGCTCCACCTCCATCCTGG CGGTAATGAA CCACATGCAGGAAGCAACTCTGAACCATGCGAAAAGCGTAGGTATCCTGGGCGATGGTTT CGGCACTACT CTGGAGATGTCCAAACGTGATCTGATGTGGGTTGTTCGCCGTACCCATGTCGCGGTTGAA CGCTACCCGA CCTGGGGCGATACGGTTGAAGTGGAATGCTGGATCGGCGCGTCCGGCAACAACGGCATGC GTCGCGATTT CCTGGTTCGCGATTGTAAGACGGGCGAGATTCTGACCCGTTGCACGTCCCTGAGCGTTCT GATGAATACC CGTACCCGTCGTCTGAGCACCATCCCGGACGAAGTTCGCGGTGAAATTGGCCCGGCATTC ATCGATAACG TTGCAGTAAAAGACGATGAAATCAAGAAACTGCAGAAACTGAATGACTCTACCGCGGACT ACATCCAGGG TGGTCTGACCCCGCGCTGGAACGACCTGGACGTGAACCAGCACGTCAACAACCTGAAATA CGTAGCTTGG GTATTCGAAACGGTCCCGGATTCTATCTTCGAATCTCACCACATCAGCTCCTTCACCCTG GAATACCGTC GTGAGTGTACCCGTGACTCCGTTCTGCGCTCTCTGACCACGGTATCCGGCGGTAGCTCTG AAGCCGGTCT GGTTTGCGATCACCTGCTGCAGCTGGAAGGCGGCAGCGAGGTTCTGCGTGCTCGTACTGA GTGGCGTCCG AAGCTGACTGACTCTTTCCGCGGCATCTCTGTTATCCCGGCAGAGCCTCGTGTGTAAGAG CTCGAGGAGG TTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCG ACGACGAGCA GTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACC GTTGCCCGCC GTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTC ACCGGCTACG GTGACCGCCCGGCGCTGGGATACCGCGCCCGTGA¾CTGGCCACCGACGAGGGCGGGCGC ACCGTGACGCG TCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGC&AG CGGTCGCCGCGGCC CTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTTC GCGAGTCCCG ATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGCAGC ACAACGCACC GGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGC CGAATACCTC GACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGAC CATCACCCCG AGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCA TCGCCGTCAC CACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTACACCGC CGACCATGAT CAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATG TACACCGAGG CGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCA ACGTCAACTT CATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGG AACCAGTTAC TTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACC GAACTCGGCC TGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGG TCACGCAGGG CGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGG CGGACGCGTG ATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTCGACATC ACCCTGGGCG CACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGA TCGTGCGGCC ACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCACCGACAA GCCCTACCCG CGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGCCCCGAG GTCACCGCGA GCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCG ACCACCTGGT GTACGTGGACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGC CAACCTGGAG GCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGCGAGCGC AGTTTCCTTC TGGCCGTGGTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAGG CCGCGCTGGC CGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCCGGCCGA TTTCATCGTC GAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTGCTGCGG CCCAACCTCA AAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGCAGGCCA ACCAGTTGCG CGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGCCGCTGC CACGATCCTC GGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGATTCCCTG TCGGCGCTGA CACTTTCGAACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGA ACCCGGCCAC CAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCC GAGTTTCACC ACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGACAAGTTC ATCGACGCCG AAACGCrCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGGTGTTGC TCTCGGGCGC CAaCGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGG CGGCACCCTC ATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTAC GACACCGATC CCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTG ACATCGGCGA CCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGACCTGGT GGTGCATCCG GCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTCGTGGGC ACGGCCGAGG TGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTGTCCACCGTGTCGG TGGCCATGGG GATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCCGCTCGA CGGCGGATAC GCCAaCGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCCCACGAT CTGTGCGGGC TGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCGGTCAGG TCAACGTGCC AGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCGGTCGTT CTACATCGGA GACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCG GTCACGACGC TCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACG GGATCTCCCT GGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTA CGACGACTGG GTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAGACCGTA CTGCCGCTGC TGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGGAGGTGT TCCACGCCGC GGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCTGATCGA CAAGTACATA CGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCCACAAGGAGGTTTTTACAATGAAA ACGACCCACA CCAGCTTACCATTTGCCGGCCACACGTTACATTTCGTCGAATTTGATCCGGCGAACTTTT GTGAACAAGA CCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCCGTAAGCGTAAAACTGA ACATCTGGCC GGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCTACAAATGCGTGCCGGCCATT GGTGAACTGC GTCAACCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCACTGCGGTACTACCGCGT TGGCGGTTGT GTCTCGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTGTCCAGACGGCACGCGA GCTGACGGAC AACATCATTACCCCGGCAGAGCACGAGCGTCTGGCGGACTGTGGTCTGGCGTTCAGCCTG GCGCTGACCC TGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATCCAAACCGATGCGGGCT TCCTGGATTA TCAAATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTGAGAATGAGATGTTTGC CGTCCATTGG CAGATTAAAGAGAAAATCGTTATCACCCTGTGCCAGCACGACTGAGAATTCGGTTTTCCG TCCTGTCTTG ATTTTCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGCATTTGTTTTTGTTTATTGCA AAAACAAAAA ATATTGTTAC¾AATTTTTACAGGCTATTAAGCCTACCGTCATAAATAATTTGCCATTTA CTAGTTTTTAA TTAACCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGTGGCGGTTTTCATGGCT TGTTATGACT GTTTTTTTGGGGTACAGTCTATGCCTCGGGCATCCAAGCAGCAAGCGCGTTACGCCGTGG GTCGATGTTT GATGTTATGGAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACAAAGTTAAA CATCATGAGG GAAGCGGTGATCGCCGAAGTATCGACTCAACTATCAGAGGTAGTTGGCGTCATCGAGCGC CATCTCGAAC CGACGTTGCTGGCCGTACATTTGTACGGCTCCGCAGTGGATGGCGGCCTGAAGCCACACA GTGATATTGA TTTGCTGGTTACGGTGACCGTAAGGCTTGATGAAACAACGCGGCGAGCTTTGATCAACGA CCTTTTGGAA ACTTCGGCTTCCCCTGGAGAGAGCGAGATTCTCCGCGCTGTAGAAGTCACCATTGTTGTG CACGACGACA TCATTCCGTGGCGTTATCCAGCTAAGCGCGAACTGCAATTTGGAGAATGGCAGCGCAATG ACATTCTTGC AGGTATCTTCGAGCCAGCCACGATCGACATTGATCTGGCTATCTTGCTGACAAAAGCAAG AGAACATAGC GTTGCCTTGGTAGGTCCAGCGGCGGAGGAACTCTTTGATCCGGTTCCTGAACAGGATCTA TTTGAGGCGC TAAATGAAACCTTAACGCTATGGAACTCGCCGCCCGACTGGGCTGGCGATGAGCGAAATG TAGTGCTTAC GTTGTCCCGCATTTGGTACAGCGCAGTAACCGGCAAAATCGCGCCGAAGGATGTCGCTGC CGACTGGGCA ATGGAGCGCCTGCCGGCCCAGTATCAGCCCGTCATACTTGAAGCTAGACAGGCTTATCTT GGACAAGAAG AAGATCGCTTGGCCTCGCGCGCAGATCAGTTGGAAGAATTTGTCCACTACGTGAAAGGCG AGATCACCAA GGTAGTCGGCAAATAATGTCTAACAATTCGTTCAAGCCGACGCCGCTTCGCGGCGCGGCT TAACTCAAGC

GrTAGATGCACTAAGCACATAATTGCTCACAGCCAAACTATCAGGTCAAGTCTGCTT TTATTATTTTTAA GCGTGCATAaTAAGCCCTACACAAATTGGGAGATATATCATGAGGCGCGCCACGAGAAAG AGTTATGACA AATTAAAATTCTGACTCTTAGATTATTTCCAGAGAGGCTGATTTTCCCAATCTTTGGGAA AGCCTAAGTT TTTAGATTCTATTTCTGGATACATCTCAAAAGTTCTTTTTAAATGCTGTGCAAAATTATG CTCTGGTTTA ATTCTGTCTAAGAGATACTGAATACAACATAAGCCAGTGAAAATTTTACGGCTGTTTCTT TGATTAATAT CCTCCAATACTTCTCTAGAGAGCCATTTTCCTTTTAACCTATCAGGCAATTTAGGTGATT CTCCTAGCTG TATATTCCAGAGCCTTGAATGATGAGCGCAAATATTTCTAATATGCGACAAAGACCGTAA CCAAGATATA AAAAACTTGT AGGTAATTGGAAATGAGTATGTATTTTTTGTCGTGTCTTAGATGGTAATAAATTTGTGT ACATTCTAGATAACTGCCCAAAGGCGATTATCTCCAAAGCCATATATGACGGCGGTAGTA GAGGATTTGT GTACTTGTT CGATAATGCCCGATAAATTCTTCTACTTTTTTAGATTGGCAATATTGAGTAATCGAATCG ATTAATTCTTGATGCTTCCCAGTGTCATAAAATAAACTTTTATTCAGATACCAATGAGGA TCATAATCAT GGGAGTAGTGATAAATCATTTGAGTTCTGACTGCTACTTCTATCGACTCCGTAGCATTAA AAATAAGCAT TCTCAAGGATTTATCAAACTTGTATAGATTTGGCCGGCCCGTCAAAAGGGCGACACCCCA TAATTAGC.ee GGGCGAAAGGCCCAGTCTTTCGACTGAGCCTTTCGTTTTATTTGATGCCTGGCAGTTCCC TACTCTCGCA TGGGGAGTCCCCACACTACCATCGGCGCTACGGCGTTTCACTTCTGAGTTCGGCATGGGG TCAGGTGGGA CCACCGCGCTACTGCCGCCAGGCAAACAAGGGGTGTTATGAGCCATATTCAGGTATAAAT GGGCTCGCGA TAATGTTCaGAATTGGTTAATTGGTTGTAACaCTGACCCCTATTTGTTTATTTTTCTAAA TACaTTOUU. TATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAA GAATATGAGT ATTC^CATT CCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTTGCTCACCCAG AAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCG AACTGGATCT CAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCAC TTTTAAAGTT CTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGC ATACACTATT CTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGA CAGTAAGAGA ATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAAC GATCGGAGGA

AGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCGATGG CAACAACGTTGCG CAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGAT GGAGGCGGAT AAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAA TCCGGAGCCG GTGAGCGTGGTTCTCGCGGTATCATCGCAGCGCTGGGGCCAGATGGTAAGCCCTCCCGTA TCGTAGTTAT CTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGG TGCCTCACTG ATTAAGCAT GGT

carboxylic ATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCGACGACGAG CAGTCGACCC

GCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACCGTTGCCCG CCGTGGTCGA CGCGGCGCaC_¾AACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTCACCGGC TACGGTGACCGC reductase CCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCGGGCGCACCGTGACG CGTCTGCTGC amplified CGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCAAGCGGTCGCCGCGG CCCTGCGCCA from CLIIACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTTCGCGAGT CCCGATTACCTG

Mycobacterium, ACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGCAGCACAACGCA CCGGTCAGCC

GGCTCGCCCaaTCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGCCGAATACCT CGACCTCGC sniegm&tis . AGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGACCATCACCC CGAGGTCGAC

GACCaCCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCATCGCCGTC ACCACCCTGG ACGCGATCG∞GACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTACACCGCCGACCAT GATCAGCGCCT CGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATGTACACCGA GGCGATGGTG GCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCAACGTCAAC TTCATGCCGC TCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGGAACCAGTT ACTTCGTACC GGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACCGAACTCGG CCTGGTTCCG CGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGGTCACGCAG GGCGCCGACG AACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGGCGGACGCG TGATCACCGG ATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTCGACATCACCCTGGG CGCACACATC GTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGATCGTGCGG CCACCGGTGA TCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTO.GCACCGACAAGCCCTACC CGCGTGGCGA ACTGCTGGTCaGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGCCCCGAGGTCACCGC GAGCGTCTTC GACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCGACCACCTG GTGTACGTGG ACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGCCAACCTGG AGGCGGTGTT CTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGCGAGCGCAGTTTCCT TCTGGCCGTG GTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAGGCCGCGCTG GCCGACTCGC TGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCCGGCCGATTTCATCG TCGAGACCGA GCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTGCTGCGGCCCAACCT CAAAGACCGC TACGGGCJ-GCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGCAGGCCAACCAGTT GCGCGAACTGC GGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGCCGCTGCCACGATCC TCGGCACCGG GAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGATTCCCTGTCGGCGCT GACACTTTCG AACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGAACCCGGCC ACCAACCTCG CCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCCGAGTTTCA CCACCGTGCA CGGCGCGGAC^CACCGAGATCCGGGCGAGTGAGCTGACCCTGGACAAGTTCATCGACGCC GAAACGCTC CGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGGTGTTGCTCTCGGGC GCCAACGGCT GGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGGCGGCACCC TCATCACGAT CGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTACGACACCGA TCCCGAGTTG TCCCGCCGC TCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTGACATCGGCGACCCGAATC TGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGACCTGGTGGTGCATC CGGCAGCGCT GGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTCGTGGGCACGGCCGA GGTGATCAAG CTGGCCCTCACCGAACGGATC-ftAGCCCGTCACGTACCTGTCCACCGTGTCGGTGGCCA TGGGGATCCCCG ACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCCGCTCGACGGCGGAT ACGCCAACGG CTACGGCJ-ACaGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCCCACGATCTGTGCG GGCTGCCCGTG GCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCGGTCAGGTCAACGTG CCAGACATGT TCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCGGTCGTTCTACATCG GAGACGGTGA GCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCGGTCACGAC GCTCGGCGCG CAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACGGGATCTCC CTGGATGTGT TCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTACGACGACT GGGTGCGTCG GTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAGACCGTACTGCCGCT GCTGCACGCG TTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGA¾CCCACGGAGGTGTTCCACGC CGCGGTGCGCA CCGCGA&GGTGGGCCCGGG&G&C&TCCCGCACCTCGACG& GGCGCTG&TCG&CaAGT&C&T&CGCGATCT GCGTGAGTTCGGTCTGATCTGA

eodon- ATGCAGCAACTGACCGATC&AAGCAAAGAACTGGACTTC&AGAGCGAGACGT ACAAAGACGCCTATAGCC optimized GCATTAACGCGATCGTCATTGAAGGCGAACAAGAGGCGCATGAAAACTACATCACCCTGG CGCAGCTGCT

GCCTGAGAGCCACGACGAACTGATTCGCCTGAGCAAAATGGAGAGCCGTCACAAGAAAGG TTTTGAGGCG

Nostoc TGTGGCCGCAATCTGGCGGTGACCCCGGACCTGCAATTTGCGAAGGAGTTCTTTAGCGGT CTGCACCAGA punctiforme ATTTCCAGACGGCCGCAGCCGAGGGCAAAGTCGTCACTTGTTTGTTGATCCAGAGCCTGA TTATTGAATG C!Si. CTTTGCTATTGCGGCGTACAACATTTACATTCCGGTCGCCGATGACTTTGCGCGTAAAAT CACGGAAGGT

GTTGTCAAAGAGGAGTATTCCCACCTGAATTTCGGTGAAGTGTGGTTGAAGGAACATTTT GCGGAATCTA

A&GCCGA&TTGGAACTGGC&AATCGCCAG&ACCTGCCGATCGTT TGG&AGATGCTGAACCAAGTGGAAGG TGATGCACATACGATGGCGATGGAGAAGGACGCATTGGTTGAGGACTTTATGATTCAGTA TGGCGAAGCA CTGTCCAATATCGGTTTCAGCACCCGTGATATCATGCGTCTGAGCGCCTATGGCCTGATC GGTGCCTAA

codon- ATGGAGTGGAAACCAAAACCGAAACTGCCTCAGCTGCTGGATGACCACTTCGGTCTGCAC GGCCTGGTTT optiiaized TCCGTCGTACCTTCGCTATCCGTTCTTACGAAGTCGGCCCTGATCGCTCCACCTCCATCC TGGCGGTAAT

GAACCACATGCAGGAAGCAACTCTGAACCATGCGAAAAGCGTAGGTATCCTGGGCGATGG TTTCGGCACT

Umbel1ula.ria ACTCTGGAGATGTCCAAACGTGATCTGATGTGGGTTGTTCGCCGTACCCATGTCGCGGTT GAACGCTACC

CGACCTGGGGCGATACGGTTGAAGTGGAATGCTGGATCGGCGCGTCCGGC&ACAAC GGCATGCGTCGCGA f tSj _a (without TTTCCTGGTTCGCGATTGTAAGACGGGCGAGATTCTGACCCGTTGCACGTCCCTGAGCGT TCTGATGAAT leader ACCCGTACCCGTCGTCTGAGCACCATCCCGGACGAAGTTCGCGGTGAAATTGGCCCGGCA TTCATCGATA

ACGTTGCAGTAAAAGACGATGAAATCAAGAAACTGCAGAAACTGAATGACTCTACCGCGG ACTACATCCA

sequence) . GGGTGGTCTGACCCCGCGCTGGAACGACCTGGACGTGAACCAGCACGTCAACAACCTGAA ATACGTAGCT

TGGGTATTCGAAACGGTCCCGGATTCTATCTTCGAATCTCACCACATCAGCTCCTTCACC CTGGAATACC GTCGTGAGTGTACCCGTGACTCCGTTCTGCGCTCTCTGACCACGGTATCCGGCGGTAGCT CTGAAGCCGG TCTGGTTTGCGATCACCTGCTGCAGCTGGAAGGCGGCAGCGAGGTTCTGCGTGCTCGTAC TGAGTGGCGT CCGAAGCTGACTGACTCTTTCCGCGGCATCTCTGTTATCCCGGCAGAGCCTCGTGTGTAA

codon- ATGGACCGTAAAAGCAAGCGTCCGGACATGCTGGTTGATTCCTTTGGTCTGGAAAGCACC GTGCAGGACG optiitt zed GTCTGGTTTTCCGTCAGTCTTTCTCCATTCGTAGCTATGAGATTGGTACTGATCGTACCG CCTCTATCGA

AACCCTGATGAATCACCTGCAAGAAACCTCTCTGAACCATTGTAAGTCTACTGGCATCCT GCTGGACGGT

Cuphea TTCGGTCGTACCCTGGAGATGTGCAAACGCGACCTGATTTGGGTAGTGATCAAAATGCAG ATCAAAGTTA fiooJ eiT ana ACCGTTATCCGGCATGGGGTGATACCGTTGAAATCAACACCCGCTTTTCTCGTCTGGGCA AAATCGGTAT fjziilS GGGCCGTGACTGGCTGATCTCTGACTGTAACACTGGTGAAATTCTGGTTCGTGCTACTAG CGCATACGCG

(without ATGATGAACaAGAAAACCCGTCGCCTGAGCAAGCTGCCGTACGAGGTCCACCAGGAGATT GTTCCGCTGT

TTGTAGACAGCCCAGTGATTGAGGATTCTGACCTGAAAGTGCATAAATTCAAAGTGAAGA CCGGTGACAG CATCCAAAAAGGCCTGACCCCAGGTTGGAACGATCTGGACGTTAACCAGCACGTTTCCAA CGTGAAGTAT

sequence) . ATCGGTTGGATTCTGGAGAGCATGCCGACCGAGGTCCTGGAAACCCAGGAGCTGTGTTCC CTGGCGCTGG

AGTACCGCCGTGAGTGCGGCCGTGACAGCGTGCTGGAGTCTGTGACCGCTATGGACCCAA GCAAAGTTGG TGTTCGTAGCCAGTACCAGCACCTGCTGCGTCTGGAAGACGGTACTGCTATCGTGAACGG TGCAACTGAA TGGCGTCCTAAAAACGCGGGTGCAAACGGTGCTATCAGCACCGGTAAAACCTCTAACGGT AACTCCGTGA GCTAA

cesdon- ATGAAaACGACCCACACCAGCTTACCATTTGCCGGCCACACGTTACATTTCGTCGAATTT GATCCGGCGA optimized E. ACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCC GTAAGCGTAA

AACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCTACAA ATGCGTGCCG

co2i enfcD. GCCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCAC TGCGGTACTA

CCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTG TCCAGACGGC ACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAGCGTCTGGCGGACTGTGG TCTGGCGTTC AGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATC CAAACCGATG CGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTG AGAATGAGAT GTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACCCTGTGCCAGCACGACTG A

plasmid TAGAAaAaCTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCAGGATTATCAATA CCATATTTTT pAQ4 : : P ( apcB} GAAAAAGCCGTTTCTGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAA GATCCTGGTA

TCGGTCTGCGATTCCGACTCGTCCAACATCAATACAACCTATTAATTTCCCCTCGTCAAA AATAAGGTTA

~3,dMsp _U ~eisaC. TCAAGTGAGAAATCACCATGAGTGACGACTGAATCCGGTGAGAATGGCAAAAGTTTATGC ATTTCTTTCC

AGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAAC CGTTATTCAT TCGTGATTGCGCCTGAGCGAGGCGAAATACGCGATCGCTGTTAAAAGGACAATTACAAAC AGGAATCGAG TGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATAT TCTTCTAATA CCTGGAACGCTGTTTTTCCGGGGATCGCAGTGGTGAGTAACCATGCATCATCAGGAGTAC GGATAAAATG CTTGATGGTCGGAAGTGGCATAAATTCCGTCAGCCAGTTTAGTCTGACCATCTCATCTGT AACATCATTG GCAACGCTACCTTTGCCATGTTTCAGAAACAACTCTGGCGCATCGGGCTTCCCATACAAG CGATAGATTG TCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATACCCATATAAATCAGCATCCA TGTTGGAATT

TATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAA CAAATAGGGGTCA GTGTTACAACCAATTAACCAATTCTGAACATTATCGCGAGCCCATTTATACCTGAATATG GCTCATAACA CCCCTTGTTTGCCTGGCGGCAGTAGCGCGGTGGTCCCACCTGACCCCATGCCGAACTCAG AAGTGAAACG CCGTAGCGCCGATGGTAGTGTGGGGACTCCCCATGCGAGAGTAGGGAACTGCCAGGCATC AAATAAAACG AAaGGCTCAGTCGAAAGACTGGGCCTTTCGCCCGGGCTAATTAGGGGGTGTCGCCCTTTA CACGTACTTA GTCGCTGAAGGCCTCACTGGCCCCTGCAGGGATGGTGGAATGCTGGTTATCTGGTGGGGA TTAAGTGGTG TTTTACTAAAGCTTGAACAACTCAAGAAAGATTATATTCGCAATAACTGCCAATAATCCC AGCATCTTGA GAAAATCCAGGAAACCGGGGGCAAAACACCAGCAAGAAGCCAGCAGACTATCACCAAATC CCCAGCGTAC AGCTAGAAATAACTGAGCAGTTGTATTCAATTACCTTCTGGTCAAGCCGAGGAAATTTCC CCACACCTTA TACACCTCTGGA¾GGTTTTTTTGACG&AGCGC&A¾ATATCCACA¾TCGG CTGGGGACTTCTTCTGTCAGA AaATGGCAGSA&TTTTTGAATGTGTTGGCGATCGCCCTCATCAATGATTATTAGAG AACTTTTGTCCCTG ATGTTGGGAATACTCTTGATGACAATTGTGATTGCTCAA&GAAGA&AGA&am p;ATTTGGAGTAA&TCTCTAA& AGGGGACTGA&ATATTTGTATGGTCAGCATGACCACTG&AATGGAGAG& ;AGTCT&AGACAGTAGATGTCT TAGATATAAGCCTCATTAGAAGCCATGCCATAAAACAGATTTTGTGGATGAAACAACTTG AAATAGTTCA GTTGTAGACCATGTTATAAACATTTATTCTTAACACAGTGACACATTAATGACTCATATA TCCGTCCAAA AMMCTAaAATGTTTGTAAATTTAGTTTTGCGGCCGCGTCGACTTCGTTATAAAATAAACT TAACAAAT CTATACCCACCTGTAGAGAAGAGTCCCTGAATATCAAAATGGTGGGATAAAAAGCTCAAA AAGGAAAGTA GGCTGTGGTTCCCTAGGCAACAGTCTTCCCTACCCCACTGG&A&CTA& AAAAACGAG&AAAGTTCGCACC GAACATCAATTGCATAATTTTAGCCCTAAAACATAAGCTGAACGAAACTGGTTGTCTTCC CTTCCCAATC CAGGACAATCTGAG&ATCCCCTGC&ACATTACTT&ACA&AAA&a mp;GCAGG&ATA&A&TTAAC&AGATGTAAC AGACATAAGTCCCATCACCGTTGTATAAAGTTAACTGTGGGATTGCAAAAGCATTCAAGC CTAGGCGCTG AGCTGTTTGAGCATCCCGGTGGCCCTTGTCGCTGCCTCCGTGTTTCTCCCTGGATTTATT TAGGTAATAT CTCTCATAaATCCCCGGGTAGTTAACGAAAGTTAATGGAGATCAGTAACAATAACTCTAG GGTCATTACT TTGGACTCCCTCAGTTTATCCGGGGGAATTGTGTTTAAGAAAATCCCAACTCATAAAGTC AAGTAGGAGA TTAaTCATATGCAGCAACTGACCGATCAAAGCAAAGAACTGGACTTCAAGAGCGAGACGT ACAAAGACGC CTATAGCCGCATTAACGCGATCGTCATTGAAGGCGAACAAGAGGCGCATGAAAACTACAT CACCCTGGCG CAGCTGCTGCCTGAGAGCCACGACGAACTGATTCGCCTGAGC&AAATGGAGAGCCG TCAC&AGAAAGGTT TTGAGGCGTGTGGCCGCAATCTGGCGGTGACCCCGGACCTGCAATTTGCGAAGGAGTTCT TTAGCGGTCT GCACCAGAATTTCCAGACGGCCGCAGCCGAGGGCAAAGTCGTCACTTGTTTGTTGATCCA GAGCCTGATT ATTGAATGCTTTGCTATTGCGGCGTACAACATTTACATTCCGGTCGCCGATGACTTTGCG CGTAAAATCA CGGAAGGTGTTGTCAAAGAGGAGTATTCCCACCTGAATTTCGGTGAAGTGTGGTTGAAGG AACATTTTGC GGAATCTAAAGCCGAATTGGAACTGGCAAATCGCCAGAACCTGCCGATCGTTTGGAAGAT GCTGAACCAA GTGGAAGGTGATGCACATACGATGGCGATGGAGAAGGACGCATTGGTTGAGGACTTTATG ATTCAGTATG GCGAAGCACTGTCC&ATATCGGTTTCAGCACCCGTGATATCATGCGTCTGAGCGCC TATGGCCTGATCGG TGCCTAACTCGAGCAATTCGGTTTTCCGTCCTGTCTTGATTTTCAAGCAAACAATGCCTC CGATTTCTAA TCGGAGGCATTTGTTTTTGTTTATTGCAAAAACAAAA&ATATTGTTACA&AT TTTTACAGGCTATTA&GC CTACCGTCATAAATAATTTGCCATTTACTAGTTTTAATTAACGTGCTATAATTATACTAA TTTTATAAGG AGGAAAAAATATGGGCATTTTTAGTATTTTTGTAATCAGCACAGTTCATTATCAACCAAA CAAAAAATAA GTGGTTATAaTGAATCGTTAATAAGCAAAATTCATATAACCAAATTAAAGAGGGTTATAA TGAACGAGAA AAATATAAAACACAGTCAAAACTTTATTACTTCAAAACATAATATAGATAAAATAATGAC AAATATAAGA TTAAaTGAaCATGATAATATCTTTGAAATCGGCTCAGGAAAAGGCCATTTTACCCTTGAA TTAGTAAAGA GGTGTAATTTCGTAACTGCCATTGAAATAGACCATAAATTATGCAAAACTACAGAAAATA AACTTGTTGA TCACGATAATTTCCAAGTTTT&A&C&AGGATATATTGCAGTTT& A&TTTCCTA&A&ACC&ATCCTAT&AA ATATATGGTAATATACCTTATAACATAAGTACGGATATAATACGCAAAATTGTTTTTGAT AGTATAGCTA ATGAGATTTATTTAATCGTGGAATACGGGTTTGCTAAAAGATTATTAAATAC&AAA CGCTCATTGGCATT ACTTTTAaTGGCAGAAGTTGATATTTCTATATTAAGTATGGTTCCAAGAGAATATTTTCA TCCTAAACCT AAAGTGAATAGCTCACTTATCAGATTAAGTAGAAAAAAATCAAGAATATCACACAAAGAT AAACAAAAGT ATAATTATTTCGTTATGAAATGGGTTAACAAAGAATACAAGAAAATATTTACAAAAAATC AATTTAACAA TTCCTTAAAACATGCAGGAATTGACGATTTAAACAATATTAGCTTTGAACAATTCTTATC TCTTTTCAAT AGCTATAAATTATTTAATAAGTAAGTTAAGGGATGCATAAACTGCATCCCTTAACTTGTT TTTCGTGTGC CTATTTTTTGTGGCGCGCCCAGTTTCCTTTACTGGCCCTAAAGTCGCTGTGGCTAGGGTT CCGAAGGGGC ATTATTGGCTCGCGGCTTTACAACCTTGAT&AGGAGAGAGATGACAGTTTTTTTTC TCTTTTGCTTAGTA AAACAGCAAATTTAAGGCATGTTAAAGAGCAGTAGAACGAAATGGTTGAGCCGGCCTCGA TACACTCAAT TAACTACTAATAGCTTCAATAAATTTTGGGACGATTGAAGCTATTTTTTTGAAAATCAAC TCTTAATATC TCCTGTCTCAAAAGAGTTAATTGCTAAACAAAAGCCAGTTTCAGCGAAAAATCTAGAGTT TTATAGGTTC GTTCTCAGTACAGGACAAAAAGTTTGAAAAGGATAGAGGGAGAGGGTTTGATGGAAATAA GCACAAATCA ATCAAGCCCTCATGAATCAGATTAGCG&AATTCGCCGCC&ATTGCGACCTCA TCTCGGATGGCATGGAGC CAGACTGTCATTTATCGCCCTCTTCCTGGTGGCACTGTTCCGAGCAAAAACCGTCAATCT CGCCAAACTC GCCACCGTCTGGGGAGGC&ATGCAGCAG&AGAGTCT&ATTAC&A ACGCATGCAGCGATTCTTTCAGTCCT TTGACGTCAACATGGACAAAATCGCCAGGATGGTAATGAATATCGCGGCTATCCCGCAAC CTTGGGTCTT AAGCATCGACCGCACCAACGGCCGGCCTACATGGCCCGTCAATCGAAGGGCGACACAAAA TTTATTCTAA ATGCATAATAAATACTGATAACATCTTATAGTTTGTATTATATTTTGTATTATCGTTGAC ATGTATAATT TTGATATCAAAAACTGATTTTCCCTTTATTATTTTCGAGATTTATTTTCTTAATTCTCTT TAACAAACTA GAAaTATTGTATATACAAAAAATCATAAATAATAGATGAATAGTTTAATTATAGGTGTTC ATCAATCGAA AAAGCAACGTATCTTATTTAAAGTGCGTTGCTTTTTTCTCATTTATAAGGTTAAATAATT CTCATATATC AAGCAAAGTGACAGGCGCCCTT&A&TATTCTGAC&A&TGCTCTT TCCCTA&ACTCCCCCCAT&A&A&A&C CCGCCGAAGCGGGTTTTTACGTTATTTGCGGATTAACGATTACTCGTTATCAGAACCGCC CAGGGGGCCC GAGCTTAAGACTGGCCGTCGTTTTACAACACAGAAAGAGTTTGTAGAAACGCAAAAAGGC CATCCGTCAG GGGCCTTCTGCTTAGTTTGATGCCTGGCAGTTCCCTACTCTCGCCTTCCGCTTCCTCGCT CACTGACTCG CTGCGCTCGGTCGTTCGGCTGCGGCGAGCGGTATCAGCTCACTCAAAGGCGGTAATACGG TTATCCACAG

AaTCAGGGGATAACGCAGGAAAGAACATGTGAGCAAAAGGCCAGCAAAAGGCCAGGAACC GTAAAAAGGC CGCGTTGCTGGCGTTTTTCCATAGGCTCCGCCCCCCTGACGAGCATCACAAAAATCGACG CTCAAGTCAG AGGTGGCGAAACCCGACAGGACTATAAAGATACCAGGCGTTTCCCCCTGG&AGCTC CCTCGTGCGCTCTC CTGTTCCGACCCTGCCGCTTACCGGATACCTGTCCGCCTTTCTCCCTTCGGGAAGCGTGG CGCTTTCTCA TAGCTCACGCTGTAGGTATCTCAGTTCGGTGTAGGTCGTTCGCTCCAAGCTGGGCTGTGT GCACG&ACCC CCCGTTCAGCCCGACCGCTGCGCCTTATCCGGTAACTATCGTCTTGAGTCCAACCCGGTA AGACACGACT TATCGCCACTGGCAGCAGCCACTGGTAACAGGATTAGCAGAGCGAGGTATGTAGGCGGTG CTACAGAGTT CTTGAaGTGGTGGGCTAACTACGGCTACACTAGAAGAACAGTATTTGGTATCTGCGCTCT GCTGAAGCCA GTTACCrTCGGAAAAAGAGTTGGTAGCTCTTGATCCGGCAAACAAACCACCGCTGGTAGC GGTGGTTTTT TTGTTTGCAAGCAGCAGATTACGCGCAGAAAAAAAGGATCTCAAGAAGATCCTTTGATCT TTTCTACGGG GTCTGACGCTCAGTGGAACGACGCGCGCGTAACTCACGTTAAGGGATTTTGGTCATGAGC TTGCGCCGTC CCGTCAAGTCAGCGT&ATGCTCTGCTTT

AAAAGCAGAGCATTACGCTGACTTGACGGGACGGCGCAAGCTCATGACCAAAATCCCTTA ACGTGAGTTA

pAQ3 : : P (nirQ7

TCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATCAA 5 -f tB _m ~carB- GAGCTACCftACTCTTTTTCCGAAGGT&ACTGGCTTCAGCAGAGCGCAGATACCA& amp;ATACTGTTCTTCTAG enfcD-SpecR. TGTAGCCGTAGTT&GCCCACC&CTTC&&G¾ACTCTGT&G CACCGCCT&C&T&CCTCGCTCTGCT&&TCCT

GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG GATAAGGCGC&GCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCC&GCT TGGAGCGAACGACCTACA CCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAA CGCCTGGTAT CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCG TCAGGGGGGC GGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGC CTTTTGCTCA CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTG AGCTGATACC GCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCATCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT GTTGTAAAACGACGGCCAGTCTTAAGCTCGGGCCCCCTGGGCGGTTCTGATAACGAGTAA TCGTTAATCC

AATATTTAa&GGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTT ATAAATGAGAAAAAAGC AACGCACrTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTATAATTAAACTAT TCATCTATTA TTTATGATTTTTTGTATATACAATATTTCTAGTTTGTTAAAGAGAATTAAGAAAATAAAT CTCGAAAATA ATAAAGGGAAAATCAGTTTTTGATATCAAAATTATACATGTCAACGATAATACAAAATAT AATACAAACT ATAAGATGTTATCAGTATTTATTATGCATTTAGAATAAATTTTGTGTCGCCCTTCGCTGA ACCTGCAGGC GAGCATTTCAACGATGATGAATGGGACGGCGAACCCACTGAACCCGTCGCCATTGACCCA GAACCGCGCA AAGAACGGGAAAAAATTGATCTCGATCTGGAGGATGAACCAGAGGAAAACCGCAAACCGC AAAAAATCAA AGTGAAGTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTCAAACCACAACTTTTTG GGATGCTGAT GGTAAACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG AAGCCGAACTACGCACCATCTGGGGGAAACCCGATACCCGTAAATCGTTCCTGACCGGAC TCGCGGAAAA AGGCTACGGTGACACCCAACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAAGTGA TGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC TGATTTTCTCGAAGTACACCGGAAAGCAGCAAGAATTTTTAGATTTTGTCCTAGACCAAT ACATTCGAGA AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCAAAC CGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG

ArGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCTTG TAGCAATTGC TACTAAAAACTGCGATCGCTGCTGAAATGAGCTGGAATTTTGTCCCTCTCAGCTCAAAAA GTATCAATGA TTACTTAATGTTTGTTCTGCGCAAACTTCTTGCAGAACATGCATGATTTACAAAAAGTTG TAGTTTCTGT TACCAATTGCGAATCGAGAACTGCCTAATCTGCCGAGTATGCGATCCTTTAGCAGGAGGA AAACCATATG GAGTGGAAACCAAAACCGAAACTGCCTCAGCTGCTGGATGACCACTTCGGTCTGCACGGC CTGGTTTTCC GTCGTACCTTCGCTATCCGTTCTTACGAAGTCGGCCCTGATCGCTCCACCTCCATCCTGG CGGTAATGAA CCACATGCAGGAAGCAACTCTGAACCATGCGAAAAGCGTAGGTATCCTGGGCGATGGTTT CGGCACTACT CTGGAGATGTCCAAACGTGATCTGATGTGGGTTGTTCGCCGTACCCATGTCGCGGTTGAA CGCTACCCGA CCTGGGGCGATACGGTTGAAGTGGAATGCTGGATCGGCGCGTCCGGCAACAACGGCATGC GTCGCGATTT CCTGGTTCGCGATTGTAAGACGGGCGAGATTCTGACCCGTTGCACGTCCCTGAGCGTTCT GATGAATACC CGTACCCGTCGTCTGAGCACCATCCCGGACGAAGTTCGCGGTGAAATTGGCCCGGCATTC ATCGATAACG

TrGCAGTAAAAGACGATGAAATCAAGAAACTGCAGAAACTGAATGACTCTACCGCGGACT ACATCCAGGG TGGTCTGACCCCGCGCTGGAACGACCTGGACGTGAACCAGCACGTCAACAACCTGAAATA CGTAGCTTGG GTATTCGAAACGGTCCCGGATTCTATCTTCGAATCTCACCACATCAGCTCCTTCACCCTG GAATACCGTC GTGAGTGTACCCGTGACTCCGTTCTGCGCTCTCTGACCACGGTATCCGGCGGTAGCTCTG AAGCCGGTCT GGTTTGCGATCACCTGCTGCAGCTGGAAGGCGGCAGCGAGGTTCTGCGTGCTCGTACTGA GTGGCGTCCG AAGCTGACTGACTCTTTCCGCGGCATCTCTGTTATCCCGGCAGAGCCTCGTGTGTAAGAG CTCGAGGAGG TTTTTACAaTGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCG ACGACGAGCA GTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACC GTTGCCCGCC GTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTC ACCGGCTACG GTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCGGGCGCA CCGTGACGCG TCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCAAGCGGT CGCCGCGGCC CTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTTC GCGAGTCCCG ATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGCAGC ACAACGCACC GGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGC CGAATACCTC GACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGAC CATCACCCCG AGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCA TCGCCGTCAC CACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTACACCGC CGACCATGAT CAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATG TACACCGAGG CGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCA ACGTCAACTT CATGCCGCT LAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGGAACCAGTTA C TTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACC GAACTCGGCC TGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGG TCACGCAGGG CGCCGACGAaCTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGG CGGACGCGTG ATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTCGACATC ACCCTGGGCG CACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGA TCGTGCGGCC ACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCACCGACAA GCCCTACCCG CGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGCCCCGAG GTCACCGCGA GCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCG ACCACCTGGT GTACGTGGACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGC CAACCTGGAG GCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGCGAGCGC AGTTTCCTTC TGGCCGTGGTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAGG CCGCGCTGGC CGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCCGGCCGA TTTCATCGTC GAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTGCTGCGG CCCAACCTCA AAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGCAGGCCA ACCAGTTGCG CGAACTGCGGGGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGCCGCTGC CACGATCCTC GGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGATTCCCTG TCGGCGCTGA CACTTTCGAaCCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGA ACCCGGCCAC CAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCC GAGTTTCACC ACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGAC&A GTTCATCGACGCCG AAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGGTGTTGC TCTCGGGCGC CAACGGCTGGGTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGG CGGCACCCTC ATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTAC GACACCGATC CCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTG ACATCGGCGA CCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGACCTGGT GGTGCATCCG GCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTCGTGGGC ACGGCCGAGG TGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTGTCCACCGTGTCGG TGGCCATGGG GATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCCGCTCGA CGGCGGATAC GCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCCCACGAT CTGTGCGGGC TGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCGGTCAGG TCAACGTGCC AGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCGGTCGTT CTACATCGGA GACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCG GTCACGACGC TCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACG GGATCTCCCT GGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTA CGACGACTGG GTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAGACCGTA CTGCCGCTGC TGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGGAGGTGT TCCACGCCGC GGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCTGATCGA CAAGTACATA CGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCCACAAGGAGGTTTTTACAATGAAA ACGACCCACA CCAGCTTACCATTTGCCGGCCACACGTTACATTTCGTCGAATTTGATCCGGCGAACTTTT GTGAACAAGA CCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCCGTAAGCGTAAAACTGA ACATCTGGCC GGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCTACAAATGCGTGCCGGCCATT GGTGAACTGC GTCAACCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCACTGCGGTACTACCGCGT TGGCGGTTGT GTCTCGCCAGGCGATCGGTATTGATATTGAAGAGATATTCTCTGTCCAGACGGCACGCGA GCTGACGGAC AACATCATTACCCCGGCAGAGCACGAGCGTCTGGCGGACTGTGGTCTGGCGTTCAGCCTG GCGCTGACCC TGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATCCAAACCGATGCGGGCT TCCTGGATTA TCAAATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTGAGAATGAGATGTTTGC CGTCCATTGG CAGATTAAaGAGAAAATCGTTATCACCCTGTGCCAGCACGACTGAGAATTCGGTTTTCCG TCCTGTCTTG ATTTTCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGCATTTGTTTTTGTTTATTGCA AAAACAAAAA ATATTGTTACAAATTTTTACAGGCTATTAAGCCTACCGTCATAAATAATTTGCCATTTAC TAGTTTTTAA TTAACCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGTGGCGGTTTTCATGGCT TGTTATGACT GTTTTTTTGGGGTACAGTCTATGCCTCGGGCATCCAAGCAGCAAGCGCGTTACGCCGTGG GTCGATGTTT GATGTTATGGAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACAAAGTTAAA CATCATGAGG GAAGCGGTGATCGCCGAAGTATCGACTCAACTATCAGAGGTAGTTGGCGTCATCGAGCGC CATCTCGAAC CGACGTTGCTGGCCGTACATTTGTACGGCTCCGCAGTGGATGGCGGCCTGAAGCCACACA GTGATATTGA TTTGCTGGTTACGGTGACCGTAAGGCTTGATGAAACAACGCGGCGAGCTTTGATCAACGA CCTTTTGGAA ACTTCGGCTTCCCCTGGAGAGAGCGAGATTCTCCGCGCTGTAGAAGTCACCATTGTTGTG CACGACGACA TCATTCCGTGGCGTTATCCAGCTAAGCGCGAACTGCAATTTGGAGAATGGCAGCGCAATG ACATTCTTGC AGGTATCTTCGAGCCAGCCACGATCGACATTGATCTGGCTATCTTGCTGACAAAAGCAAG AGAACATAGC GTTGCCTTGGTAGGTCCAGCGGCGGAGGAACTCTTTGATCCGGTTCCTGAACAGGATCTA TTTGAGGCGC TAAATGAAACCTTAACGCTATGGAACTCGCCGCCCGACTGGGCTGGCGATGAGCGAAATG TAGTGCTTAC GTTGTCCCGCATTTGGTACAGCGCAGTAACCGGCAAAATCGCGCCGAAGGATGTCGCTGC CGACTGGGCA ATGGAGCGCCTGCCGGCCCAGTATCAGCCCGTCATACTTGAAGCTAGACAGGCTTATCTT GGACAAGAAG

AaGATCGCTTGGCCTCGCGCGCAGATCAGTTGGAAGAATTTGTCCACTACGTGAAAG GCGAGATCACCAA GGTAGTCGGCAAATAATGTCTAACAATTCGTTCAAGCCGACGCCGCTTCGCGGCGCGGCT TAACTCAAGC GTTAGATGCACTAAGCACATAATTGCTCACAGCCAAACTATCAGGTCAAGTCTGCTTTTA TTATTTTTAA GCGTGCATAATAAGCCCTACACAAATTGGGAGATATATCATGAGGCGCGCCACGAGAAAG AGTTATGACA AATTAAAATTCTGACTCTTAGATTATTTCCAGAGAGGCTGATTTTCCCAATCTTTGGGAA AGCCTAAGTT TTTAGATTCTATTTCTGGATACATCTCAAAAGTTCTTTTTAAATGCTGTGCAAAATTATG CTCTGGTTTA ATTCTGTCTAAGAGATACTGAATACAACATAAGCCAGTGAAAATTTTACGGCTGTTTCTT TGATTAATAT CCTCCAATACTTCTCTAGAGAGCCATTTTCCTTTTAACCTATCAGGCAATTTAGGTGATT CTCCTAGCTG TATATTCCAGAGCCTTGAATGATGAGCGCAAATATTTCTAATATGCGACAAAGACCGTAA CCAAGATATA AAaAaCTTGTTAGGTAATTGGAAATGAGTATGTATTTTTTGTCGTGTCTTAGATGGTAAT AAATTTGTGT ACATTCTAGATAACTGCCCAAAGGCGATTATCTCCAAAGCCATATATGACGGCGGTAGTA GAGGATTTGT GTACTTGTTTCGATAATGCCCGATAAATTCTTCTACTTTTTTAGATTGGCAATATTGAGT AATCGAATCG ATTAATrcrTGATGCTTCCCAGTGTCATAAAATAAACTTTTATTCAGATACCAATGAGGA TCATAATCAT GGGAGTAGTGATAAATCATTTGAGTTCTGACTGCTACTTCTATCGACTCCGTAGCATTAA AAATAAGCAT TCTCAAGGATTTATCAAACTTGTATAGATTTGGCCGGCCCGTCAAAAGGGCGACACCCCA TAATTAGCCC GGGCGAAAGGCCCAGTCTTTCGACTGAGCCTTTCGTTTTATTTGATGCCTGGCAGTTCCC TACTCTCGCA TGGGGAGTCCCCACACTACCATCGGCGCTACGGCGTTTCACTTCTGAGTTCGGCATGGGG TCAGGTGGGA CCACCGCGCTACTGCCGCCAGGCAAACAAGGGGTGTTATGAGCCATATTCAGGTATAAAT GGGCTCGCGA TAATGTTCAGAATTGGTTAATTGGTTGTAACACTGACCCCTATTTGTTTATTTTTCTAAA TACATTCAAA TATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAA GAATATGAGT ATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTT GCTCACCCAG AAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCG AACTGGATCT CAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCAC TTTTAAAGTT CTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGC ATACACTATT

CrCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCA TGACAGTAAGAGA ATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAAC GATCGGAGGA

AGCTGAaTGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCGATGG CAACAACGTTGCG CAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGAT GGAGGCGGAT AAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAA TCCGGAGCCG GTGAGCGTGGTTCTCGCGGTATCATCGCAGCGCTGGGGCCAGATGGTAAGCCCTCCCGTA TCGTAGTTAT

CrACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGAT AGGTGCCTCACTG ATTAAGCATTGGT A¾ftAGCAGAGCATTACGCTGACTTGACGGGACGGCGCAAGCTCATGACCA&AAT CCCTTAACGTGAGTTA pAQ3: :P(nir07

TCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATCAA GAGCTACCA&CTCTTTTTCCGA&GGT¾ACTGGCTTC&GCAGAGCGC& amp;G&T&CCA&A ^, ACTGT ^, C ^, TCT&G enfcD-SpeeR, TGTAGCCGTAGTTAGCCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC TGCTAATCCT

GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG GATAaGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACA CCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGG&am p;AACGCCTGGTAT CTTTATAGTCCTGTCGGGTTTCGCCACCTCTGACTTGAGCGTCGATTTTTGTGATGCTCG TCAGGGGGGC GGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCTGGC CTTTTGCTCA CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTG AGCTGATACC GCrCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCATCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT

GrTGTAAAACGACGGCCAGTCTTAAGCTCGGGCCCCCTGGGCGGTTCTGATAACGAGTAA TCGTTAATCC GCAaATAaCGTAAAAACCCGCTTCGGCGGGTTTTTTTATGGGGGGAGTTTAGGGAAAGAG CATTTGTCAG AATATTTAAGGGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTTATAAATG AGAAAAAAGC AACGCACTTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTATAATTAAACTAT TCATCTATTA TTTATGATTTTTTGTATATACAATATTTCTAGTTTGTTAAAGAGAATTAAGAAAATAAAT CTCGAAAATA ATAAAGGGAAAATCAGTTTTTGATATCAAAATTATACATGTCAACGATAATACAAAATAT AATACAAACT ATAAGATGTTATCAGTATTTATTATGCATTTAGAATAAATTTTGTGTCGCCCTTCGCTGA ACCTGCAGGC GAGCATTTCAACGATGATGAATGGGACGGCGAACCCACTGAACCCGTCGCCATTGACCCA GAACCGCGCA

AaGAACGGGAAAAAATTGATCTCGATCTGGAGGATGAACCAGAGGAAAACCGCAAACCGC AAAAAATCAA AGTGAAGTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTCAAACCACAACTTTTTG GGATGCTGAT GGTAAACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG AAGCCGAACTACGCACCATCTGGGGGAAACCCGATACCCGTAAATCGTTCCTGACCGGAC TCGCGGAAAA AGGCTACGGTGACACCCAACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAAGTGA TGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC

AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCA AACCGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG ATGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCTTG TAGCAATTGC TACTAAAAACTGCGATCGCTGCTGAAATGAGCTGGAATTTTGTCCCTCTCAGCTCAAAAA GTATCAATGA TTACTTAATGTTTGTTCTGCGCAAACTTCTTGCAGAACATGCATGATTTACAAAAAGTTG TAGTTTCTGT TACCAATTGCGAATCGAGAACTGCCTAATCTGCCGAGTATGCGATCCTTTAGCAGGAGGA AAACCATATG GACCGTAAAAGCAAGCGTCCGGACATGCTGGTTGATTCCTTTGGTCTGGAAAGCACCGTG CAGGACGGTC TGGTTTTCCGTCAGTCTTTCTCCATTCGTAGCTATGAGATTGGTACTGATCGTACCGCCT CTATCGAAAC CCTGATGAATCACCTGCAAGAAACCTCTCTGAACCATTGTAAGTCTACTGGCATCCTGCT GGACGGTTTC GGTCGTACCCTGGAGATGTGCAAACGCGACCTGATTTGGGTAGTGATCAAAATGCAGATC AAAGTTAACC

GrTATCCGGCATGGGGTGATACCGTTGAAATCAACACCCGCTTTTCTCGTCTGGGCAAAA TCGGTATGGG CCGTGACTGGCTGATCTCTGACTGTAACACTGGTGAAATTCTGGTTCGTGCTACTAGCGC ATACGCGATG ATGAACCAGAAAACCCGTCGCCTGAGCAAGCTGCCGTACGAGGTCCACCAGGAGATTGTT CCGCTGTTTG TAGACAGCCCAGTGATTGAGGATTCTGACCTGAAAGTGCATAAATTCAAAGTGAAGACCG GTGACAGCAT CCAaAaAGGCCTGACCCCAGGTTGGAACGATCTGGACGTTAACCAGCACGTTTCCAACGT GAAGTATATC GGTTGGATTCTGGAGAGCATGCCGACCGAGGTCCTGGAAACCCAGGAGCTGTGTTCCCTG GCGCTGGAGT ACCGCCGTGAGTGCGGCCGTGACAGCGTGCTGGAGTCTGTGACCGCTATGGACCCAAGCA AAGTTGGTGT TCGTAGCCAGTACCAGCACCTGCTGCGTCTGGAAGACGGTACTGCTATCGTGAACGGTGC AACTGAATGG CGTCCTAAA&ACGCGGGTGCAAACGGTGCTATCAGCACCGGTAAAACCTCTAACGG TAACTCCGTGAGCT AAGAGCTCGAGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCA CCGAAACCGC ACTCGACGACGAGCAGTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTT CGCCGCCGCC GCACCGTTGCCCGCCGTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATC CTGCAGACCC TGTTCACCGGCTACGGTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCG ACGAGGGCGG GCGCACCGTGACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTC GCGCGTGCAA GCGGTCGCCGCGGCCCTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTC GCGACGATCG GTTTCGCGAGTCCCGATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGA GTGTTCCGCT GCAGCACAACGCACCGGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGAT CCTCACCGTG AGCGCCGA&TACCTCGACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTC GCAGCTCGTGGTGT TCGACCATCACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAAC TCGCCGGCAA GGGCATCGCCGTCACCACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGA ACCGATCTAC ACCGCCGACCATGATCAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCA CCCAAGGGTG CGATGTACACCGAGGCGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACC CCACGCCGGT CATCAaCGTCAACTTCATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGC CGTGCAGAAC GGTGGAACCAGTTACTTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCG CTGGTGCGCC CGACCGAACTCGGCCTGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCA CCGTCGACCG CCTGGTCACGCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCG TGAGCAGGTG CTCGGCGGACGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGG GCGTTCCTCG ACATCACCCTGGGCGCACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGA CACGCGACGG TGTGATCGTGCGGCCACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTA CTTCAGCACC GACAAGCCCTACCCGCGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTAC TACAAGCGCC CCGAGGTCACCGCGAGCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGG CCGAGACCGC ACCCGACCACCTGGTGTACGTGGACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGA GTTCGTGGCG GTCGCCAACCTGGAGGCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTAC GGCAACAGCG AGCGCAGTTTCCTTCTGGCCGTGGTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATC CGGCCGCGCT CAAGGCCGCGGTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTA CGAGGTGCCG GCCGArTTCATCGTCGAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTC GGAAAACTGC TGCGGCCCAaCCTCAAAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCG CGGCCACGCA GGCCAACCAGTTGCGCGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCCT CACCCAGGCC GCTGCCACGATCCTCGGCACCGGG&GCG&GGTGGCATCCG&CGCCCAC TTCACCGACCTGGGCGGGGATT CCCTGTCGGCGCTGACACTTTCG&ACCTGCTGAGCGATTTCTTCGGTTTCG& AGTTCCCGTCGGCACCAT CGTGAACCCGGCCACCAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGC GGGTGACCGC AGGCCGAGTTTCACCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTG ACCCTGGACA AGTTCATCGACGCCGAAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGC CACGGACGGT GTTGCTCTCGGGCGCCAACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACG CCTGGCACCT GTCGGCGGCACCCTCATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGG CTGACCCAGG CCTACGACACCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGC GGGTGGTCGC CGGTGACATCGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGC CGAGGTCGAC CTGGTGGTGCATCCGGCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGC CCCAACGTCG TGGGCACGGCCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACC TGTCCACCGT GTCGGTGGCCATGGGGATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCC GGTGCGCCCG CTCGACGGCGGATACGCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTG CGGGAGGCCC ACGATCTGTGCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGC GCTACCGCGG TCAGGTCAACGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGT CGCGCCGCGG TCGTTCTACATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGAT TTCGTGGCCG AGGCGGTCACGACGCTCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGA ACCCGCACGA CGACGGGATCTCCCTGGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGA CCGGGTCGAC GACTACGACGACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGC CGCGCACAGA CCGTACTGCCGCTGCTGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCG AACCCACGGA GGTGTTCCACGCCGCGGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGA CGAGGCGCTG ATCGACAAGTACATACGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCCACAAGGAG GTTTTTACAA TGAaAaCGACCCACACCAGCTTACCATTTGCCGGCCACACGTTACATTTCGTCGAATTTG ATCCGGCGAA CTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCCG TAAGCGTAAA ACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCTACAAA TGCGTGCCGG CCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCACT GCGGTACTAC CGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTGT CCAGACGGCA CGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAGCGTCTGGCGGACTGTGGT CTGGCGTTCA GCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATCC AAACCGATGC GGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTGA GAATGAGATG TTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACCCTGTGCCAGCACGACTGA GAATTCGGTT TTCCGTCCTGTCTTGATTTTCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGCATTTG TTTTTGTTTA TTGCAAAAACAAAAAATATTGTTACAAATTTTTACAGGCTATTAAGCCTACCGTCATAAA TAATTTGCCA TTTACTAGTTTTTAATTAACCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGTG GCGGTTTTCA TGGCTTGTTATGACTGTTTTTTTGGGGTACAGTCTATGCCTCGGGCATCCAAGCAGCAAG CGCGTTACGC CGTGGGTCGATGTTTGATGTTATGGAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCC TAAACAAAG TTAaACATCATGAGGGAAGCGGTGATCGCCGAAGTATCGACTCAACTATCAGAGGTAGTT GGCGTCATCG AGCGCCATCTCGAACCGACGTTGCTGGCCGTACATTTGTACGGCTCCGCAGTGGATGGCG GCCTGAAGCC ACACAGTGATATTGATTTGCTGGTTACGGTGACCGTAAGGCTTGATGAAACAACGCGGCG AGCTTTGATC AACGACCTTTTGGAAACTTCGGCTTCCCCTGGAGAGAGCGAGATTCTCCGCGCTGTAGAA GTCACCATTG TTGTGCACGACGACATCATTCCGTGGCGTTATCCAGCTAAGCGCGAACTGCAATTTGGAG AATGGCAGCG CAATGACATTCTTGCAGGTATCTTCGAGCCAGCCACGATCGACATTGATCTGGCTATCTT GCTGACAAAA GCAAGAGAACATAGCGTTGCCTTGGTAGGTCCAGCGGCGGAGGAACTCTTTGATCCGGTT CCTGAACAGG ATCTATTTGAGGCGCTAAATGAAACCTTAACGCTATGGAACTCGCCGCCCGACTGGGCTG GCGATGAGCG AAATGTAGTGCTTACGTTGTCCCGCATTTGGTACAGCGCAGTAACCGGCAAAATCGCGCC GAAGGATGTC GCTGCCGACTGGGCAATGGAGCGCCTGCCGGCCCAGTATCAGCCCGTCATACTTGAAGCT AGACAGGCTT ATCTTGGACAAGAAGAAGATCGCTTGGCCTCGCGCGCAGATCAGTTGGAAGAATTTGTCC ACTACGTGAA AGGCGAGATCACCAAGGTAGTCGGCAAATAATGTCTAACAATTCGTTCAAGCCGACGCCG CTTCGCGGCG CGGCTTAACTCAAGCGTTAGATGCACTAAGCACATAATTGCTCACAGCCAAACTATCAGG TCAAGTCTGC TTTTATTATTTTTAAGCGTGCATAATAAGCCCTACACAAATTGGGAGATATATCATGAGG CGCGCCACGA GAAAGAGTTATGACAAATTAAAATTCTGACTCTTAGATTATTTCCAGAGAGGCTGATTTT CCCAATCTTT GGGAAAGCCTAAGTTTTTAGATTCTATTTCTGGATACATCTCAAAAGTTCTTTTTAAATG CTGTGCAAAA TTATGCTCTGGTTTAATTCTGTCTAAGAGATACTGAATACAACATAAGCCAGTGAAAATT TTACGGCTGT TTCTTTGATTAATATCCTCCAATACTTCTCTAGAGAGCCATTTTCCTTTTAACCTATCAG GCAATTTAGG TGATTCTCCTAGCTGTATATTCCAGAGCCTTGAATGATGAGCGCAAATATTTCTAATATG CGACAAAGAC CGrAACCAAGATATAAAAAACTTGTTAGGTAATTGGAAATGAGTATGTATTTTTTGTCGT GTCTTAGATG GTAATAAATTTGTGTACATTCTAGATAACTGCCCAAAGGCGATTATCTCCAAAGCCATAT ATGACGGCGG TAGTAGAGGATTTGTGTACTTGTTTCGATAATGCCCGATAAATTCTTCTACTTTTTTAGA TTGGCAATAT TGAGTAATCGAATCGATTAATTCTTGATGCTTCCCAGTGTCATAAAATAAACTTTTATTC AGATACCAAT GAGGATCATAATCATGGGAGTAGTGATAAATCATTTGAGTTCTGACTGCTACTTCTATCG ACTCCGTAGC ATTAAAAATAAGCATTCTCAAGGATTTATCAAACTTGTATAGATTTGGCCGGCCCGTCAA AAGGGCGACA CCCCATAaTTAGCCCGGGCGAAAGGCCCAGTCTTTCGACTGAGCCTTTCGTTTTATTTGA TGCCTGGCAG TTCCCTACTCTCGCATGGGGAGTCCCCACACTACCATCGGCGCTACGGCGTTTCACTTCT GAGTTCGGCA TGGGGTCAGGTGGGACCACCGCGCTACTGCCGCCAGGCAAACAAGGGGTGTTATGAGCCA TATTCAGGTA TAAATGGGCTCGCGATAATGTTCAGAATTGGTTAATTGGTTGTAACACTGACCCCTATTT GTTTATTTTT CTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATA ATATTGAAAA

TTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGGTG CACGAGTGGGTTA CATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTT TCCAATGATG AGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAG CAACTCGGTC GCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATC TTACGGATGG CATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAA CTTACTTCTG

ATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGA TGCCTGTAGCGAT GGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACA ATTAATAGAC TGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGG TTTATTGCTG ATAAATCCGGAGCCGGTGAGCGTGGTTCTCGCGGTATCATCGCAGCGCTGGGGCCAGATG GTAAGCCCTC CCGTATCGTAGTTATCTACACGACGGGG&GTC&GGC&ACT&TGG &TGA¾CGA¾ATAGACAGATCGCTGAG ATAGGTGCCTCACTGiRTTAAGCATTGGT

carbos;ylic GAGCTCGAGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACC GAAACCGCAC acid TCGACGACGAGCAGTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCG CCGCCGCCGC

ACCGTTGCCCGCCGTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCT GCAGACCCTG

reductase

amplified GCACCGTGACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGC GCGTGCAAGC from GGTCGCCGCGGCCCTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGC GACGATCGGT

Mycobac vm TTCGCGAGTCCCGATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGT GTTCCGCTGC fcer1

AGCACAACGCACCGGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCC TCACCGTGAG

swegmatis . CGCCGAATACCTCGACCTCGCAGTCGAATCCGTGCGGGACGTC&ACTCGGTGTCGC AGCTCGTGGTGTTC

GACCATCACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTC GCCGGCAAGG GCATCGCCGTCACCACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAAC CGATCTACAC CGCCGACCATGATCAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACC CAAGGGTGCG ATGTACACCGAGGCGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCC ACGCCGGTCA TCAACGTCAACTTCATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCG TGCAGAACGG TGGAACCAGTTACTTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCT GGTGCGCCCG

TGGTCACGCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGC GTGAGCAGGTGCT CGGCGGACGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGC GTTCCTCGAC ATCACCCTGGGCGCACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACA CGCGACGGTG TGATCGTGCGGCCACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACT TCAGCACCGA CAaGCCCTACCCGCGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTA CAAGCGCCCC GAGGTCACCGCGAGCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCC GAGACCGCAC CCGACCACCTGGTGTACGTGGACCGTCGC&ACAACGTCCTC&AACTCGCGCA GGGCGAGTTCGTGGCGGT CGCCAACCTGGAGGCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGG CAACAGCGAG

AGGCCGCGCTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCT ACGAGGTGCCGGC CGATTTCATCGTCGAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGG AAAACTGCTG CGGCCCAACCTCAAAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCG GCCACGCAGG

TGCCACGATCCTCGGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCT GGGCGGGGATTCC

TGAACCCGGCCACC&ACCTCGCCC&ACTCGCCCAGCACATCGAGGCGCA GCGCACCGCGGGTGACCGCAG GCCGAGTTTCACCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGAC CCTGGACAAG TTCATCGACGCCG&AACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGA GCCACGGACGGTGT TGCTCTCGGGCGCCAACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCC TGGCACCTGT CGGCGGCACCCTCATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCT GACCCAGGCC TACGACACCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGG GTGGTCGCCG GTGACATCGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCG AGGTCGACCT

GGCACGGCCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTAC CTGTCCACCGTGT CGGTGGCCATGGGGATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGG TGCGCCCGCT CGACGGCGGATACGCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCG GGAGGCCCAC GATCTGTGCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGC TACCGCGGTC AGGTCAACGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCG CGCCGCGGTC GTTCTACATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTT CGTGGCCGAG GCGGTCACGACGCTCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAAC CCGCACGACG

CTACGACGACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCG CCGCGCACAGACC GTACTGCCGC.TGCTGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGA ACCCACGGAGG TGTTCCACGCCGCGGTGCGCACCGCG&AGGTGGGCCCGGGAGACATCCCGCACCTC GACGAGGCGCTGAT CGACAAGTACATACGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACC

codon-

CTATTAACGCCATTGTGATCGAAGGCGAGCAAGAAGCATACCAAAACTACCTGGACA TGGCGCAACTGCT

optiittized

Cyanothecs

ad .

GTTTGCGATTGCAGCCTAC&ACATTTACATTCCAGTGGCTGATCCGTTTGCACGT& amp;AAATCACCGAGGGT

AGCTC

codon- GAGCTCGAGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACC GAAACCGCAC optimized E, TCGACGACGAGCAGTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCG CCGCCGCCGC coli tssA^ and TTCACCGGCTACGGTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGAC GAGGGCGGGC E. coli entD GCACCGTGACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGC GCGTGCAAGC genes . GGTCGCCGCGGCCCTGCGCCAC&ACTTCGCGCAGCCGATCTACCCCGGCGACGCCG TCGCGACGATCGGT

TTCGCGAGTCCCGATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGT GTTCCGCTGC AGCACAACGCACCGGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCC TCACCGTGAG CGCCGAaTACCTCGACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCT CGTGGTGTTC GACCATCACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTC GCCGGCAAGG GCATCGCCGTCACCACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAAC CGATCTACAC CGCCGACCATGATCAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACC CAAGGGTGCG ATGTACACCGAGGCGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCC ACGCCGGTCA TCAACGTCAACTTCATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCG TGCAGAACGG TGGAACCAGTTACTTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCT GGTGCGCCCG ACCGAACTCGGCCTGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACC GTCGACCGCC TGGTCACGCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTG AGCAGGTGCT CGGCGGACGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGC GTTCCTCGAC ATCACCCTGGGCGCACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACA CGCGACGGTG TGATCGTGCGGCCACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACT TCAGCACCGA CAAGCCCTACCCGCGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTA CAAGCGCCCC GAGGTCACCGCGAGCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCC GAGACCGCAC CCGACCACCTGGTGTACGTGGACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGT TCGTGGCGGT CGCCAACCTGGAGGCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGG CAACAGCGAG CGCAGTTTCCTTCTGGCCGTGGTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCG GCCGCGCTCA AGGCCGCGCTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACG AGGTGCCGGC CGATTTCATCGTCGAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGG AAAACTGCTG CGGCCCAACCTCAAAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCG GCCACGCAGG CCAACCAGTTGCGCGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCA CCCAGGCCGC TGCCACGATCCTCGGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGG CGGGGATTCC CTGTCGGCGCTGACACTTTCGAACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTC GGCACCATCG TGAACCCGGCCACCAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGG GTGACCGCAG GCCGAGTTTCACCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGAC CCTGGACAAG TTCATCGACGCCGAAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCA CGGACGGTGT TGCTCTCGGGCGCCAACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCC TGGCACCTGT CGGCGGCACCCTCATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCT GACCCAGGCC TACGACACCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGG GTGGTCGCCG GTGACATCGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCG AGGTCGACCT GGTGGTGCATCCGGCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCC CAACGTCGTG GGCACGGCCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTG TCCACCGTGT CGGTGGCCATGGGGATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGG TGCGCCCGCT CGACGGCGGATACGCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCG GGAGGCCCAC GATCTGTGCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGC TACCGCGGTC AGGTCAACGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCG CGCCGCGGTC GTTCTACATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTT CGTGGCCGAG GCGGTCACGACGCTCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAAC CCGCACGACG ACGGGATCTCCCTGGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACC GGGTCGACGA CTACGACGACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCG CGCACAGACC GTACTGCCGCTGCTGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAA CCCACGGAGG TGTTCCACGCCGCGGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACG AGGCGCTGAT CGACAAGTACATACGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCAGGAGGTTTTT ACAATGGCTG ATACTTTGTTGATTTTGGGTGATTCTCTCTCTGCAGGCTACCGTATGTCCGCGAGCGCGG CATGGCCGGC TCTGCTGAACGATAAGTGGCAGAGCAAGACCAGCGTGGTCAATGCGAGCATCAGCGGCGA TACCAGCCAG CAGGGTCTGGCACGTCTGCCAGCGCTGCTGAAGCAACACCAGCCGCGTTGGGTGCTGGTT GAACTGGGCG GCAATGACGGTCTGCGTGGTTTTCAGCCGCAGCAGACCGAACAAACGTTGCGTCAGATTC TGCAGGACGT CAAGGCGGCTAACGCGGAACCGCTGCTGATGCAAATTCGCCTGCCGGCGAATTATGGTCG TCGTTACAAC GAGGCTTTCAGCGCCATTTATCCTAAACTGGCTAAAGAGTTTGACGTGCCGCTGCTGCCG TTCTTCATGG AAGAGGTCTACCTGAAACCGCAATGGATGCAAGACGACGGTATTCATCCGAATCGTGATG CACAACCTTT CATCGCGGATTGGATGGCGAAGCAATTGCAACCGCTGGTGAACCATGACTCGTAAAAGCT TGTTGCTGCA TGCAGGAGGTTTTTACAATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCACACGT TACATTTCGT CGAATTTGATCCGGCGAACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCA GCTGCAGCAC GCAGGCCGTAAGCGTAAAACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTG CGCGAGTACG GCTACAAATGCGTGCCGGCCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGAAGTTT ACGGTTCCAT CTCCCACTGCGGTACTACCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATAT TGAAGAGATA TTCTCTGTCCAGACGGCACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAG CGTCTGGCGG ACTGTGGTCTGGCGTTCAGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGT TCAAGGCTTC CGAGATCCAAACCGATGCGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACA GGTTATCATT CACCGTGAGAATGAGATGTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACC CTGTGCCAGC ACGACTGAGAATTC

plasittid AAAAGCAGAGCATTACGCTGACTTGACGGGACGGCGCAAGCTCATGACCAAAATCCCTTA ACGTGAGTTA pAQ3: :P{nir07 CGCGCGCGTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAG ATCCTTTTTT 5 TCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATCAA -adm-carB- GAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACT GTTCTTCTAG t sA^-sntD- TGTAGCCGTAGTTAGCCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC TGCTAATCCT

GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG GATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACA CCGAACTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGGAGAA AGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAA CGCCTGGTAT

GGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCT GGCCTTTTGCTCA CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTG AGCTGATACC GCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCArCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT GTTGTAAAACGACGGCCAGTCTTAAGCTCGGGCCCCCTGGGCGGTTCTGATAACGAGTAA TCGTTAATCC GCAAATAACGTAAAAACCCGCTTCGGCGGGTTTTTTTATGGGGGGAGTTTAGGGAAAGAG CATTTGTCAG AATATTTAAGGGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTTATAAATG AGAAAAAAGC AACGCACTTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTAT&ATT&am p;A&CTATTCATCTATTA TTTATGATTTTTTGTATATACAATATTTCTAGTTTGTTAAAGAGAATTAAGAAAATAAAT CTCGAAAATA ATAAAGGGAAAATCAGTTTTTGATATCAAAATTATACATGTCAACGATAATACAAAATAT AATACAAACT ATAAGATGTTATCAGTATTTATTATGCATTTAGAATAAATTTTGTGTCGCCCTTCGCTGA ACCTGCAGGC GAGCATTTCAACGATGATGAATGGGACGGCGAACCCACTGAACCCGTCGCCATTGACCCA GAACCGCGCA AAGAaCGGGAAAAAATTGATCTCGATCTGGAGGATGAACCAGAGGAAAACCGCAAACCGC AAAAAATCAA AGTGAAGTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTCAAACCACAACTTTTTG GGATGCTGAT GGTAAACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG AAGCCGAACTACGCACCATCTGGGGGAAACCCGATACCCGTAAATCGTTCCTGACCGGAC TCGCGGAAAA AGGCTACGGTGACACCCAACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAAGTGA TGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC

AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCA AACCGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG ATGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCTTG TAGCAATTGC TACTAAAAACTGCGATCGCTGCTGAAATGAGCTGGAATTTTGTCCCTCTCAGCTCAAAAA GTATCAATGA TTACTTAATGTTTGTTCTGCGCAAACTTCTTGCAGAACATGCATGATTTACAAAAAGTTG TAGTTTCTGT TACCAATTGCGAATCGAGAACTGCCTAATCTGCCGAGTATGCGATCCTTTAGCAGGAGGA AAACCATATG CAAGAACTGGCCCTGAGAAGCGAGCTGGACTTCAATAGCGAAACCTATAAAGATGCGTAT AGCCGTATTA ACGCCATTGTGATCGAAGGCGAGCAAGAAGCATACCAAAACTACCTGGACATGGCGCAAC TGCTGCCGGA GGACGAGGCTGAGCTGATTCGTTTGAGCAAGATGGAGAACCGTCACAAAAAGGGTTTTCA AGCGTGCGGC AAGAACCTCAATGTGACTCCGGATATGGATTATGCACAGCAGTTCTTTGCGGAGCTGCAC GGCAATTTTC AGAAGGCTAAAGCCGAGGGTAAGATTGTTACCTGCCTGCTCATCCAAAGCCTGATCATCG AGGCGTTTGC GATTGCAGCCTACAACATTTACATTCCAGTGGCTGATCCGTTTGCACGTAAAATCACCGA GGGTGTCGTC AAGGATGAGTATACCCACCTGAATTTCGGCGAAGTTTGGTTGAAGGAACATTTTGAAGCA AGCAAGGCGG AGTTGGAGGACGCCAACAAAGAGAACTTACCGCTGGTCTGGCAGATGTTGAACCAGGTCG AAAAGGATGC CGAAGTGCTGGGTATGGAGAAAGAGGCTCTGGTGGAGGACTTTATGATTAGCTATGGTGA GGCACTGAGC AACATCGGCrTTTCTACGAGAGAAATCATGAAGATGAGCGCGTACGGTCTGCGTGCAGCA TAAGAGCTCG AGGAGGTTTTTACAATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCG CACTCGACGA CGAGCAGTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGC CGCACCGTTG CCCGCCGTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACC CTGTTCACCG GCTACGGTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCG GGCGCACCGT GACGCGTCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCA AGCGGTCGCC GCGGCCCTGCGCCACAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATC GGTTTCGCGA GTCCCGATTACCTGACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGC TGCAGCACAA CGCACCGGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGT GAGCGCCGAA TACCrCGACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTG TTCGACCATC ACCCCGAGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCA AGGGCATCGC CGTCACCACCCTGGACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTA CACCGCCGAC CATGATCAGCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGT GCGATGTACA CCGAGGCGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGG TCATCAACGT CAACTTCATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAA CGGTGGAACC AGTTACTTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGC CCGACCGAAC TCGGCCTGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACC GCCTGGTCAC GCAGGGCGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGT GCTCGGCGGA CGCGTGATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTC GACATCACCC TGGGCGCACACATCGTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACG GTGTGATCGT GCGGCCACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCAC CGACAAGC.ee TACCCGCGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGC CCCGAGGTCA CCGCGAGCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCG CACCCGACCA CCTGGTGTACGTGGACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGC GGTCGCCAAC CTGGAGGCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGC GAGCGCAGTT TCCTTCTGGCCGTGGTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGC TCAAGGCCGC GCTGGCCGACTCGCTGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCC GGCCGATTTC ATCGTCGAGACCGAGCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTG CTGCGGCCCA ACCTCAAAGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGC AGGCCAACCA GTTGCGCGAACTGCGGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGC CGCTGCCACG ATCCTCGGCACCGGGAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGAT TCCCTGTCGG CGCTGACACTTTCGAACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCA TCGTGAACCC GGCCACCAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCG CAGGCCGAGT TTCACCACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGAC AAGTTCATCG ACGCCGAAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGG TGTTGCTCTC GGGCGCCAACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACC TGTCGGCGGC ACCCTCATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAG GCCTACGACA CCGATCCCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCG CCGGTGACAT CGGCGACCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGA CCTGGTGGTG CATCCGGCAGCGCTGGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTC GTGGGCACGG CCGAGGTGATCAAGCTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTGTCCACCG TGTCGGTGGC CATGGGGATCCCCGACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCC GCTCGACGGC GGATACGCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCC CACGATCTGT GCGGGCTGCCCGTGGCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCG GTCAGGTCAA CGTGCCAGACATGTTCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCG GTCGTTCTAC ATCGGAGACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCC GAGGCGGTCA CGACGCTCGGCGCGCAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACG ACGACGGGAT CTCCCTGGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGA CGACTACGAC GACTGGGTGCGTCGGTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAG ACCGTACTGC CGCTGCTGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGG AGGTGTTCCA CGCCGCGGTGCGCACCGCG&AGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGG CGCTGATCGAC&AG TACATACGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCAGGAGGTTTTTACftATG GCTGATACTTT GTTGATTTTGGGTGATTCTCTCTCTGCAGGCTACCGTATGTCCGCGAGCGCGGCATGGCC GGCTCTGCTG AACGATAAGTGGCAGAGCAAGACCAGCGTGGTCAATGCGAGCATCAGCGGCGATACCAGC CAGCAGGGTC TGGCACGTCTGCCAGCGCTGCTGAAGCAACACCAGCCGCGTTGGGTGCTGGTTGAACTGG GCGGCAATGA CGGTCTGCGTGGTTTTCAGCCGCAGCAGACCGAACAAACGTTGCGTCAGATTCTGCAGGA CGTCAAGGCG GCTAACGCGGAACCGCTGCTGATGCAAATTCGCCTGCCGGCGAATTATGGTCGTCGTTAC AACGAGGCTT TCLMCGCCATTTATCCTAAACTGGCTAAAGAGTTTGACGTGCCGCTGCTGCCGTTCTTCA TGGAAGAGGT CTACCTGAAACCGCAATGGATGCAAGACGACGGTATTCATCCGAATCGTGATGCACAACC TTTCATCGCG GATTGGATGGCGAAGCAATTGCAACCGCTGGTGAACCATGACTCGTAAAAGCTTGTTGCT GCATGCAGGA GGTTTTTACAATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCACACGTTACATTT CGTCGAATTT GATCCGGCGAACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAG CACGCAGGCC GTAAGCGTAAAACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGT ACGGCTACAA ATGCGTGCCGGCCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGAAGTTTACGGTTC CATCTCCCAC TGCGGTACTACCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATATTGAAGAG ATATTCTCTG TCCAGACGGCACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAGCGTCTGG CGGACTGTGG TCTGGCGTTCAGCCTGGCGCTGACCCTGGCATTC-f^GCAAAAGAGAGCGCGTTCAAGGC TTCCGAGATC CAAACCGATGCGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACAGGTTATC ATTCACCGTG AGAATGAGATGTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACCCTGTGCC AGCACGACTG AGAATTCGGT TTCCGTCCTGTCTTGATTTTCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGCATTT GTTTTTGTTTATTGCAAAAACAAAAAATATTGTTACAAATTTTTACAGGCTATTAAGCCT ACCGTCATAA ATAATTTGCCaTTTACTAGTTTTTAATTAACC^AACCTTGACCGAACGCAGCGGTGGTAA CGGCGCAGT GGCGGTTTTCATGGCTTGTTATGACTGTTTTTTTGGGGTACAGTCTATGCCTCGGGCATC CAAGCAGCAA GCGCGTTACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGC-f^CGATGTTACGCAGCA GGGCAGTCGCC CTAAAACAAAGTTAAACATCATGAGGGAAGCGGTGATCGCCGAAGTATCGACTCAACTAT CAGAGGTAGT TGGCGTCATCGAGCGCCATCTCGAACCGACGTTGCTGGCCGTACATTTGTACGGCTCCGC AGTGGATGGC GGCCTGAAGCCacaca-GTGATATTGATTTGCTGGTTACGGTGACCGTAAGGCTTGATGA AACAACGCGGC GAGCTTTGATOU CGACCTTTTGGAAACTTCGGCTTCCCCTGGAGAGAGCGAGATTCTCCGCGCTGTAGA AGTCaCCATTGTTGTGCACGACGACATCaTTCCGTGGCGTTATCCAGCTAAGCGCGAACT GatftTTTGGA GAATGGCAGCGCAATGACATTCTTGCAGGTATCTTCGAGCCAGCCACGATCGACATTGAT CTGGCTATCT TGCTGACAaAAGCAAGAGAACATAGCGTTGCCTTGGTAGGTCCAGCGGCGGAGGAACTCT TTGATCCGGT TCCTGAACAGGATCTATTTGAGGCGCTAAATGAAACCTTAACGCTATGGAACTCGCCGCC CGACTGGGCT GGCGATGAGCKAAATGTAGTGCTTACGTTGTCCCGCATTTGGTAC-f^GCAGTAACCGGC AAAATCGCGC CGAAGGATG CGCTGCCGACTGGGCAATGGAGCGCCTGCCGGCCCAGTATCAGCCCGTCATACTTGAAGC TAGACAGGCTTATCTTGGACAAGAAGAAGATCGCTTGGCCTCGCGCGCAGATCAGTTGGA AGAATTTGTC CACTACGTGAAAGGCGAGATCACCAAGGTAGTCGGCAAATAATGTCTAACAATTCGTTCA AGCCGACGCC GCrTCGCGGCGCGGCTTAACTCAAGCGTTAGATGCACTAAGCACATAATTGCTCACAGCC AAACTATCAG GTC -AGTCTGCTTTTATTATTTTTAAGCGTGCATAATAAGCCCTACACAAATTGGGAGATATA TCATGAG GCGCGCCACGAGAAAGAGTTATGAOUU.TTAAAATTCTGACTCTTAGATTATTTCCAGAG AGGCTGATTT TCCCLAATCTTTGGGAAAGCCTAAGTTTTTAGATTCTATTTCTGGATACATCTC-ftAAA GTTCTTTTTAAAT GCTGTGCAAAATTATGCTCTGGTTTAATTCTGTCTAAGAGATACTGAATACAACATAAGC CAGTGAAAAT TTTACGGCTGTTTCTTTGATTAATATCCTCCAATACTTCTCTAGAGAGCCATTTTCCTTT TAACCTATCA GGCAATTTAGGTGATTCTCCTAGCTGTATATTCO.GAGCCTTGAATGATGAGCGCAAATA TTTCTAATAT GCGACAAAGACCGTAACCAAGATATAAAAAACTTGTTAGGTAATTGGAAATGAGTATGTA TTTTTTGTCG TGTCTTAGATGGTAATAAATTTGTGTACATTCTAGATAACTGCCCAAAGGCGATTATCTC CAAAGCCATA TATGACGGCGGTAGTAGAGGATTTGTGTACTTGTTTCGATAATGCCCGATAAATTCTTCT ACTTTTTTAG ATTGGCLAATATTGAGTAATCGAATCGATTAATTCTTGATGCTTCCCAGTGTCATAAAAT AAACTTTTATT CAGATACCAATGAGGATCATAATCATGGGAGTAGTGATAAATCATTTGAGTTCTGACTGC TACTTCTATC GACTCCGTAGCATTAAAAATAAGCATTCTC-ftAGGATTTATCAAACTTGTATAGATTTG GCCGGCCCGTCA AAAGGGCGACACCCCATAATTAGCCCGGGCGAAAGGCCCAGTCTTTCGACTGAGCCTTTC GTTTTATTTG ATGCCTGGCAGTTCCCTACTCTCGCATGGGGAGTCCCCACACTACCATCGGCGCTACGGC GTTTCACTTC TGAGTTCGGCATGGGGTCAGGTGGGACCACCGCGCTACTGCCGCCAGGCAAACAAGGGGT GTTATGAGCC ATATTCAGGTATAAATGGGCTCGCGATAATGTTCAGAATTGGTTAATTGGTTGTAACACT GACCCCTATT TGTTTATTTT CTAAATACATTCAAATATGTATCCGCTCATGAGAa^TAACCCTGATAAATGCTTCAAT AATATTGAAAAAGGAAGAATATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTT TTGCGGCATT TTGCCTTCCTGTTTTTGCTCACCC-feGAAACGCTGGTGAAAGTAAAAGATGCTGAAGAT CAGTTGGGTGCA CGAGTGGGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCC GAAGAACGTT TTCCLAATGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGAC GCCGGGCAAGA GCAACTCGG CGCCGCATACACTATTCTC^AATGACTTGGTTGAGTACTCaCCAGTCACAGAAAAGCAT CrTACGGATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAAC ACTGCGGCCA ACTTACTTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACaTGG GGGATa-TGT AACTCGCCTTGATCGTTGGGAACCGGAGCTGAATGAAGCO.TACCAAACGACGAGCGTGA CACCACGATG CCTGTAGCGATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCT TCCCGGCAAC AATTAATAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTC CGGCTGGCTG GTTTATTGCTGATAAATCCGGAGCCGGTGAGCGTGGTTCTCGCGGTATCATCGCAGCGCT GGGGCCAGAT GGTAAGCCC CCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGAC AGATCGCTGAGATAGGTGCCTCACTGATTAAGCATTGGT

N. MQQLTDQSKELDFKSETYKDAYS INAIVIEGEQEAHENYITLAQLLPESHDELI LSKMESRHKKGFEA punctiforme CGI^IAV PDLQFA EFFSGLHQNFQTAAAEGKW CLLIQSLI IECFAIAAYNIYIPVADDFAEKITEG

VVKEEYSHIJ^I3V LKEHFAES AELElLWraQNLPIV MLNQ

Adm sequence LSNIGFSTRDIMRLSAYGLIGA

(polypeptide)

N. ATGCAGCAaCTGACCGATCAAAGCAAAGAACTGGACTTCAAGAGCGAGACGTACAAAGAC GCCTATAGCC punctiforme GCATTAACGCGATCGTCATTGAAGGCGAACAAGAGGCGCATGAAAACTACATCACCCTGG CGCAGCTGCT

GCCTGAGAGC^CGACGAACTGATTCGCCTGAGCAAAATGGAGAGCCGTCACAAGAAAGGT TTTGAGGCG acta sequence TGTGGCCGCAATCTGGCGGTGACCCCGGACCTGCAATTTGCGAAGGAGTTCTTTAGCGGT CTGCACCAGA (nucleotide) , ATTTCCAGACGGCCGCAGCCGAGGGCA&AGTCGTCACTTGTTTGTTGATCCAGAGC CTGATTATTGA&TG

CTTTGCTATTGCGGCGT&CAACATTTACATTCCGGTCGCCG&TGACTTTGCG CGTAAAATC&CGGAAGGT GTTGTCAAAGAGGAGTATTCCCACCTGAATTTCGGTGAAGTGTGGTTG&AGG& ;ACATTTTGCGG&ATCTA optimized for AAGCCGAATTGGAACTGGCAAATCGCCAGAACCTGCCGATCGTTTGGAAGATGCTGAACC AAGTGGAAGG Li TGATGCACATACGATGGCGATGGAGAAGGACGCATTGGTTGAGGACTTTATGATTCAGTA TGGCGAAGCA

CTGTCCAATATCGGTTTCAGCACCCGTGATATCATGCGTCTGAGCGCCTATGGCCTGATC GGTGCCTAA

MGSSHHHHHHSQDP QQLTDQSKELDFKSETYKDAYSRINAIVIEGEQEA HEHYITLAQLLPESHDELIRLS MESKK GFEACGKNLAV PDLQFA E FFSGLHQ^FQTAAAEGKV"VTCLLIQSLIIECFAIAAYNIYIPVADBFARK

His-Tagged ITEGVVTCEEYSKLNFGEVWLKEHFAESKAELELANEQNLPIVWKMLNQVE

Adm sequence GDAHTFFFIMEKDALVEDFMIQYGEALSNIGFSTRDIMRLSAYGLIGA

(polypeptide)

N. ATGGGCAGCAGCCATCACCATCATCACCACAGCCAGGATCCGATGCAGC&ACTGAC CGATC&AAGCAAAG punctifozme AACTGGACTTCAAGAGCGAGACGTACAAAGACGCCTATAGCCGCATTAACGCGATCGTCA TTGAAGGCGA

ACAAGAGGCGCATGAAAACTACATCACCCTGGCGCAGCTGCTGCCTGAGAGCCACGACGA ACTGATTCGC

sxii sequence CTGAGCAaAaTGGAGAGCCGTCACAAGAAAGGTTTTGAGGCGTGTGGCCGCAATCTGGCG GTGACCCCGG (His-Tagged) ACCTGCAATTTGCGAAGGAGTTCTTTAGCGGTCTGCACCAGAATTTCCAGACGGCCGCAG CCGAGGGCAA (nucleotide) AGTCGTCACTTGTTTGTTGATCCAGAGCCTGATTATTGAATGCTTTGCTATTGCGGCGTA CA&CATTTAC

ATTCCGGTCGCCGATGACTTTGCGCGTAAAATCACGGAAGGTGTTGTCAAAGAGGAGTAT TCCCACCTGA ATTTCGGTGAAGTGTGGTTGAAGGAACATTTTGCGGAATCT&AAGCCGAATTGGAA CTGGC&AATCGCCA GA&CCTGCCGATCGTTTGGAAGATGCTGAACCAAGTGGAAGGTGATGCACATACGA TGGCGATGGAGAAG GACGCATTGGTTGAGGACTTTATGATTCAGTATGGCGAAGCACTGTCCAATATCGGTTTC AGCACCCGTG ATATCATGCGTCTGAGCGCCTATGGCCTGATCGGTGCC

5" - CAT CAC CAC AGO GAG GAT CCG ATG GAG CAA CTG ACC GAT CAA AGO punatlforme GAA CTG GftC TTC ^■■ 3'

acta Primer

UNI9

N. 5' - CGG CCC GCC AAG CTT TTA GGC ACC GAT CAG GCC ATA GGC GCT CAG ACG pvmctiforme CAT GAT ATC - 3 '

ac

UN2G

Plasmid pCDF GGGGAaTTGTGAGCGGATAACAATTCCCCTGTAGAAATAATTTTGTTTAACTTTAATAAG GAGATATACC npu (Table 5 ATGGGCAGCAGCCATCACCATCATCACCACAGCCAGGATCCGATGCAGCAACTGACCGAT CAAAGCAAAG

AACTGGACTTCAAGAGCGAGACGTAC&AAGACGCCTATAGCCGCATTAACGCGATC GTCATTGAAGGCGA for key) ACAAGAGGCGCATGAAAACTACATCACCCTGGCGCAGCTGCTGCCTGAGAGCCACGACGA ACTGATTCGC

CTGAGCAAAATGGAGAGCCGTCACAAG&AAGGTTTTGAGGCGTGTGGCCGC& ATCTGGCGGTGACCCCGG ACCTGCAATTTGCGAAGGAGTTCTTTAGCGGTCTGCACCAGAATTTCCAGACGGCCGCAG CCGAGGGCAA AGTCGTCACTTGTTTGTTGATCCAGAGCCTGATTATTGAATGCTTTGCTATTGCGGCGTA CAACATTTAC ATTCCGGTCGCCGATGACTTTGCGCGTAAAATCACGGAAGGTGTTGTCAAAGAGGAGTAT TCCCACCTGA ATTTCGGTGAAGTGTGGTTGAAGGAACATTTTGCGGAATCTAAAGCCGAATTGGAACTGG CAAATCGCCA GAACCTGCCGATCGTTTGGAAGATGCTG&ACC&AGTGG&AGGTGATGC ACATACGATGGCGATGGAGAAG GACGCATTGGTTGAGGACTTTATGATTCAGTATGGCGAAGCACTGTCCAATATCGGTTTC AGCACCCGTG ATATCATGCGTCTGAGCGCCTATGGCCTGATCGGTGCCT&AAGCTTGCGGCCGCAT AATGCTT&AGTCGA ACAGAAAGTAATCGTATTGTACACGGCCGCATAATCGAAATTAATACGACTCACTATAGG GGAATTGTGA GCGGATAACAATTCCCCATCTTAGTATATTAGTTAAGTATAAGAAGGAGATATACATATG GCAGATCTCA ATTGGATATCGGCCGGCCACGCGATCGCTGACGTCGGTACCCTCGAGTCTGGTAAAGAAA CCGCTGCTGC GAAATTTGAACGCCAGCACATGGACTCGTCTACTAGCGCAGCTTAATTAACCTAGGCTGC TGCCACCGCT GAGCAATAaCTAGCATAACCCCTTGGGGCCTCTAAACGGGTCTTGAGGGGTTTTTTGCTG AAACCTCAGG CATTTGAGAAGCACACGGTCACACTGCTTCCGGTAGTCAATAAACCGGTAAACCAGCAAT AGACATAAGC GGCTATTTAACGACCCTGCCCTG&ACCGACGACCGGGTCATCGTGGCCGGATCTTG CGGCCCCTCGGCTT GAACGAATTGTTAGACATTATTTGCCGACTACCTTGGTGATCTCGCCTTTCACGTAGTGG ACAAATTCTT CCAACTGATCTGCGCGCGAGGCCAAGCGATCTTCTTCTTGTCCAAGAT&AGCCTGT CTAGCTTC&AGTAT GACGGGCTGATACTGGGCCGGCAGGCGCTCCATTGCCCAGTCGGCAGCGACATCCTTCGG CGCGATTTTG CCGGTTACTGCGCTGTACCAAATGCGGGACAACGTAAGCACTACATTTCGCTCATCGCCA GCCCAGTCGG GCGGCGAGTTCCATAGCGTTAAGGTTTCATTTAGCGCCTCAAATAGATCCTGTTCAGGAA CCGGATCAAA GAGTTCCTCCGCCGCTGGACCTACCAAGGCAACGCTATGTTCTCTTGCTTTTGTCAGCAA GATAGCCAGA TCAATGTCGATCGTGGCTGGCTCGAAGATACCTGC&AGAATGTCATTGCGCTGCCA TTCTCCAAATTGCA GTTCGCGCTTAGCTGGATAACGCCACGGAATGATGTCGTCGTGCACAACAATGGTGACTT CTACAGCGCG GAGAATCTCGCTCTCTCCAGGGGAAGCCGAAGTTTCCAAAAGGTCGTTGATC&AAG CTCGCCGCGTTGTT TCATCAAGCCTTACGGTCACCGTAACCAGCAAATCAATATCACTGTGTGGCTTCAGGCCG CCATCCACTG CGGAGCCGTACAAATGTACGGCCAGCAACGTCGGTTCGAGATGGCGCTCGATGACGCCAA CTACCTCTGA TAGTTGAGTCGATACTTCGGCGATCACCGCTTCCCTCATACTCTTCCTTTTTCAATATTA TTGAAGCATT TATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAA ATAGCTAGCT CACTCGGTCGCTACGCTCCGGGCGTGAGACTGCGGCGGGCGCTGCGGACACATACAAAGT TACCCACAGA TTCCGTGGATAAGCAGGGGACTAACATGTGAGGCAAAACAGCAGGGCCGCGCCGGTGGCG TTTTTCCATA GGCTCCGCCCTCCTGCCAGAGTTCACAT&AACAGACGCTTTTCCGGTGCATCTGTG GGAGCCGTGAGGCT CAACCATGAATCTGACAGTACGGGCGAAACCCGACAGGACTTAAAGATCCCCACCGTTTC CGGCGGGTCG CTCCCTCTTGCGCTCTCCTGTTCCGACCCTGCCGTTTACCGGATACCTGTTCCGCCTTTC TCCCTTACGG GAaGTGTGGCGCTTTCTCATAGCTCACACACTGGTATCTCGGCTCGGTGTAGGTCGTTCG CTCCAAGCTG GGCTGTAAGCAAGAACTCCCCGTTCAGCCCGACTGCTGCGCCTTATCCGGTAACTGTTCA CTTGAGTCCA ACCCGGASAAGCACGGTAAAACGCCACTGGCAGCAGCCATTGGTAACTGGGAGTTCGCAG AGGATTTGTT TAGCTAftACACGCGGTTGCTCTTG&AGTGTGCGCCA&AGTCCGGCTACACT GGAAGGACAGATTTGGTTG CTGTGCTCTGCG&&AGCCAGTTACCACGGTT&AGCAGTTCCCC& ACTGACT ^, &&CCT ^, CGA ^, C&A&CCAC CTCCCCAGGTGGTTTTTTCGTTTACAGGGCAAAAGATTACGCGCAGAAAAAAAGGATCTC AAGAAGATCC TTTGATCTTTTCTACTGAACCGCTCTAGATTTCAGTGC&ATTTATCTCTTCAAATG TAGCACCTGAAGTC AGCCCCATACGATATA¾GTTGTAATTCTCATGTTAGTCATGCCCCGCGCCCACCGGAAG GAGCTGACTGG GTTGAAGGCTCTCAAGGGCATCGGTCGAGATCCCGGTGCCTAATGAGTGAGCTAACTTAC ATTAATTGCG TTGCGCTCACTGCCCGCTTTCCAGTCGGGAAACCTGTCGTGCCAGCTGCATTAATGAATC GGCCAACGCG CGGGGAGAGGCGGTTTGCGTATTGGGCGCCAGGGTGGTTTTTCTTTTCACCAGTGAGACG GGCAACAGCT GATTGCCCTTCACCGCCTGGCCCTGAGAGAGTTGCAGCAAGCGGTCCACGCTGGTTTGCC CCAGCAGGCG AAAATCCTGTTTGATGGTGGTTAACGGCGGGATATAACATGAGCTGTCTTCGGTATCGTC GTATCCCACT ACCGAGATGTCCGCACCAACGCGCAGCCCGGACTCGGTAATGGCGCGCATTGCGCCCAGC GCCATCTGAT CGTTGGCAACCAGCATCGCAGTGGGAACGATGCCCTCATTCAGCATTTGCATGGTTTGTT GAAAACCGGA CATGGCACTCCAGTCGCCTTCCCGTTCCGCTATCGGCTGAATTTGATTGCGAGTGAGATA TTTATGCCAG CCAGCCAGACGCAGACGCGCCGAGACAGAACTTAATGGGCCCGCTAACAGCGCGATTTGC TGGTGACCCA ATGCGACCAGATGCTCCACGCCCAGTCGCGTACCGTCTTCATGGGAGAAAATAATACTGT TGATGGGTGT CTGGTCAGAGACATCAAGAAATAACGCCGGAACATTAGTGCAGGCAGCTTCCACAGCAAT GGCATCCTGG TCATCCAGCGGATAGTTAATGATCAGCCCACTGACGCGTTGCGCGAGAAGATTGTGCACC GCCGCTTTAC AGGCTTCGACGCCGCTTCGTTCTACCATCGACACCACCACGCTGGCACCCAGTTGATCGG CGCGAGATTT AATCGCCGCGACAATTTGCGACGGCGCGTGCAGGGCCAGACTGGAGGTGGCAACGCCAAT CAGCAACGAC TGTTTGCCCGCCAGTTGTTGTGCCACGCGGTTGGGAATGTAATTCAGCTCCGCCATCGCC GCTTCCACTT TTTCCCGCGTTTTCGCAGAAACGTGGCTGGCCTGGTTCACCACGCGGGAAACGGTCTGAT AAGAGACACC GGCATACTCTGCGACATCGTATAACGTTACTGGTTTCACATTCACCACCCTGAATTGACT CTCTTCCGGG CGCTATCATGCCATACCGCGAAAGGTTTTGCGCCATTCGATGGTGTCCGGGATCTCGACG CTCTCCCTTA TGCGACTCCTGCATTAGGAAATTAATACGACTCACTATA

"i _* -»5 cSLCS MYWGDYLLDRIJIELGIEEIFGVPGDYNLQFLDQIISK DM WGNANELNASY ¾DGYART AAAFLT decarboxylase TFGVGELSAVNGLAGSYAEF3LPVVEIVGSPTSKVQF3EGK VHHTLADGDFKHF MHEPV AARTLLTAE

NATVEIDRVIISALLKEEKPVYINLPVDVAA&KAEKPSLPLKKENPTSNTSDQEIL NKIQESLKNAKKPIV KivD ITGHEIISFGLEF3TV QFIS T LPITTLNFG SSVDETLPSFLGIYNGKLSEPF3LKEFVESADFILMLG

(ADA65057) V LTDSSTGAFTHKLHEHK

from ISLNIDEGKIF^SIQNFDFESLISSLLDLSGIEY G YID QEDF\I'PSNALLSQDRLWQAVENLTQSN

L&ctococcus ETIVAEQGTSFFGASSIFLKPKSKFIGQPLWGSIGYTFPAALGSQIADKESRELLFIGDG SLQLWQELG

IAIREKIHPICFII™DGYT\^REIHGPNQSYM3IP^^YS LPESFGATEERWS I\¾TE!^FVSV i ctls s bsp . EAQADPIJR YWIELVLA EDAPKVL MG LFAEQNKS

lactis KF147

(polypeptide)

ketoacid MAPV IEKFVNQEERKLVSNRSATIPFGEYIF RLLSIDT SVFGVPGDFNLSLLEYLYSPSVESAGLRW decarboxylase VGTC!^LHAaYAADGYSKYSN IGCLITTYGVGELSALNGIAGSFAEN^WJilVGVA SIDSKSSNFSD

RNLHHLVPQLKDSNF GPNHKVYHDE47KDRVACSVAYLEDIETACDQTONVIR IYKYS PGYIFVPA F

ARO10 ADMSWCDHLVWPKISQQDCIVYPSENQLSDIIN ITSWIYSS TPAILGDVI,TDKYGVSNFLN LIC

(NP_Q1Q668) TGIWNFSTVM5KSVIDESf3PTYMGQYf3GKEGL QVYEHFELCDLVLHFGVDIf3EINf3GHYTFTY Pf3A I from IQFHPNYIRLVDTRQGNEQ FKGINFAPILKELYKRIDVSKLSLQY SJW QYTNETMRLEDPTNGQSSI

S3.cch ∑OiB.ycBS ITQVHLQ TMP FLNPGDVWCETGSFQFS

VRDFAFPSQLKYISQGFFLSIGMALPAALGVGIA QDHSNAKINGGNV EDYKPRLILFEGDGAAQMTIQ

csrevlslas ELSTIL CNIPLEVIIWNf3NGYTIERAIMGPTRSYNDVMSW W LFEAFGDFDGKYTf3STLIQCPSKLA

S288c L LEELKNSN RSGIELLEV LGELDFPEQL CE^TEAAALKRN K

(polypeptide)

pdc (Z . ATGAGTTATACTGTCGGTACCTATTTAGCGGAGCGGCTTGTCCAGATTGGTCTCAAGCAT CACTTCGCAG mobllis) TCGCGGGCGACTACAACCTCGTCCTTCTTGACAACCTGCTTTTGAACAAA ACATGGAGCAGGTTTATTG

CTGTAACGAACTGAACTGCGGTTTCAGTGCAGAAGGTTATGCTCGTGCCAAAGGCGCAGC AGCAGCCGTC

nucleotide GTTACCTACAGCGTCGGTGCGCTTTCCGCATTTGATGCTATCGGTGGCGCCTATGCAGAA AACCTTCCGG sequence TTATCCTGATCTCCGGTGCTCCGAACAACAATGATCACGCTGCTGGTCACGTGTTGCATC ACGCTCTTGG

CAAAACCGACTATCACTATCAGTTGGAAATGGCCAAGAACATCACGGCCGCAGCTGAAGC GATTTACACC CCAGAaGAAGCTCCGGCTAAAATCGATCACGTGATTAAAACTGCTCTTCGTGAGAAGAAG CCGGTTTATC TCGAAATCGCTTGCAACATTGCTTCCATGCCCTGCGCCGCTCCTGGACCGGCAAGCGCAT TGTTCAATGA CGAAGCCAGCGACGAAGCTTCTTTGAATGCAGCGGTTGAAGAAACCCTGAAATTCATCGC CAACCGCGAC AAAGTTGCCGTCCTCGTCGGCAGCAAGCTGCGCGCAGCTGGTGCTGAAGAAGCTGCTGTC AAATTTGCTG ATGCTCTCGGTGGCGCAGTTGCTACCATGGCTGCTGCAA&AAGCTTCTTCCCAGAA GAAAACCCGCATTA CATCGGTACCTCATGGGGTGAAGTCAGCTATCCGGGCGTTGAAAAGACGATGAAAGAAGC CGATGCGGTT ATCGCrCTGGCTCCTGTCTTCAACGACTACTCCACCACTGGTTGGACGGATATTCCTGAT CCTAAGAAAC TGGTTCTCGCTGAACCGCGTTCTGTCGTCGTTAACGGCGTTCGCTTCCCCAGCGTTCATC TGAAAGACTA

rCTGACCCGTTTGGCTCAGAAAGTTTCCAAGAAAACCGGTGCTTTGGACTTCTTCAAATC CCTCAATGCA GGTGAACTGAAGAAAGCCGCTCCGGCTGATCCGAGTGCTCCGTTGGTCAACGCAGAAATC GCCCGTCAGG TCGAAGCTCTTCTGACCCCGAACACGACGGTTATTGCTGAAACCGGTGACTCTTGGTTCA ATGCTCAGCG CATGA&GCTCCCGAACGGTGCTCGCGTTGAATATGAAATGCAGTGGGGTCACATCG GTTGGTCCGTTCCT GCCGCCTTCGGTTATGCCGTCGGTGCTCCGGAACGTCGCAACATCCTCATGGTTGGTGAT GGTTCCTTCC AGCTGACGGCTCAGGAAGTCGCTCAGATGGTTCGCCTGAAACTGCCGGTTATCATCTTCT TGATCAATAA CTATGGTTACACCATCGAAGTTATGATCCATGATGGTCCGTACAACAACATCAAGAACTG GGATTATGCC GGrCTGATGGAAGTGTTCAACGGTAACGGTGGTTATGACAGCGGTGCTGGTAAAGGCCTG AAGGCTAAAA CCGGTGGCGAACTGGCAGAAGCTATCAAGGTTGCTCTGGCAAACACCGACGGCCCAACCC TGATCGAATG CTTCATCGGTCGTGAAGACTGCACTGAAGAATTGGTCAAATGGGGTAAGCGCGTTGCTGC CGCCAACAGC CGTAAGCCTGTT&ACAAGCTCCTCTAG

Pdc ( Z , MSYTVGTYLAERLVQIGL HHFAVAGDYf3LVLLDf3LLLf3Kf^EQVYCCfffiLNCGFSAEGYARAKGAAAAV mobllis) VTYSVGALSAFDAIGGAYAENLPVILISGAPNiWroKAAGKVLHKALGKTDYKYQLEMAK NITAAAEAIYT

PEEAPAKIDHVIKTALREK PVYLEIACNIASMPCAAPGPASALFf3DEASDEASLf3AAVEETL FIAf3RD protein VAVX,VGSKLRAAGAEEAAVKFABALGGAVATMAAAKSFFPEENPHYIGTS¾G

lAIAPVEmiYSTTGOTDIPBPKKLVL&EPRSV NGVR^

sequence

GEL KAAPADPSAPLVNAEIARQVEALLTPNTTVIAETGDSWFf3AQKM LPf3GARVEYEMQWGHIG¾SVP SAFGYAVGAPERENIIM^GDGSFQLTAQEVAQWELKLPVIIFLI3fflyGyTIEV IKDGPY3fflIKi5W YA GLMEVFNGNGGYDSGAGKGLKA TGGELAEAIIWALANTDGPTLIECFIGREDCTEELV WGKRVAAAfSS RKPVNKLL

carfooxylic ATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCGACGACGAG CAGTCGACCC

GCCGCaTCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACCGTTGCCCG CCGTGGTCGA acid

CGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTCACCGGCTA CGGTGACCGC

reductase CCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCGGGCGCACCGTGACG CGTCTGCTGC amplif ed CGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCAAGCGGTCGCCGCGG CCCTGCGCCA from CAACTTCGCGGAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTTCGCGAGTCC CGATTACCTG

Mycobacterium ACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGO-GCACaACGCA CCGGTCAGCC

GGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGCCGAATACC TCGACCTCGC

sni&cpiie. ti.s AGTCGAATCCSTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGACCATCACCC CGAGGTCGAC

GACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCATCGCCGTC ACCACCCTGG ACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTACACCGCCGACCATG ATCAGCGCCT CGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATGTACACCGA GGCGATGGTG GCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCAACGTCAAC TTCATGCCGC TCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGGAACCAGTT ACTTCGTACC GGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACCGAACTCGG CCTGGTTCCG CGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGGTCACGCAG GGCGCCGACG AACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGGCGGACGCG TGATCACCGG ATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTCGACATCACCCTGGG CGCACACATC GTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGATCGTGCGG CCACCGGTGA TCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCACCGACAAGCCCTACC CGCGTGGCGA ACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGCCCCGAGGTCACCGC GAGCGTCTTC GACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCGACCACCTG GTGTACGTGG ACCGrCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGCCAACCTGG AGGCGGTGTT CTCCGGCGCGGCGCTGGTGCGCa^ATCTTCGTGTACGGCAACAGCGAGCGCAGTTTCCTT CTGGCCGTG GTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAGGCCGCGCTG GCCGACTCGC TGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCCGGCCGATTTCATCG TCGAGACCGA GCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTGCTGCGGCCCAACCT CAAAGACCGC TACGGGCLAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCC-ACGC-¾GGCCAACCA GTTGCGCGAACTGC GGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGCCGCTGCCACGATCC TCGGCACCGG GAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGATTCCCTGTCGGCGCT GACACTTTCG AACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGAACCCGGCC ACCAACCTCG CCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCCGAGTTTCA CCACCGTGCA CGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGACAAGTTCATCGACGC CGAAACGCTC CGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGGTGTTGCTCTCGGGC GCCAACGGCT GGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGGCGGCACCC TCATCACGAT CGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTACGACACCGA TCCCGAGTTG TCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTGACATCGGC GACCCGAATC TGGGCCTCACaCCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGACCTGGTGGTGCATC CGGCAGCGCT GGTC^CCaCGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTCGTGGGCACGGCCGAG GTGATCAAG CTGGCCCTCACCGAACGGATCAAGCCCGTCACGTACCTGTCCACCGTGTCGGTGGCCATG GGGATCCCCG ACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCCGCTCGACGGCGGAT ACGCCAACGG CTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCCCACGATCTGTGCGG GCTGCCCGTG GCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCGGTCAGGTCAACGTG CCAGACATGT TCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCGGTCGTTCTACATCG GAGACGGTGA GCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCGGTCACGAC GCTCGGCGCG CLAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACGGGATCTC CCTGGATGTGT TCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTACGACGACT GGGTGCGTCG GTTCGAGACC^GTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAGACCGTACTGCCGCTG CTGCACGCG TTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGGAGGTGTTCCACGCC GCGGTGCGCA CCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCTGATCGACAAGTACA TACGCGATCT GCGTGAGTTCGGTCTGATCTGA

ATGCACCATCACCACCATCATGGAGGCGGACAGCAACTGACCGATCAAAGCAAAGAA CTGGACTTCAAGA GCGAGACGTACAAAGACGCCTATAGCCGCATTAACGCGATCGTCATTGAAGGCGAACAAG AGGCGCATGA

optimi zed

AAACTACATCACCCTGGCGCAGCTGCTGCCTGAGAGCCACGACGAACTGATTCGCCTGAG CAAAATGGAG

hexahi s fcidine AGCCGTCLACLAAGAAAGGTTTTGAGGCGTGTGGCCGCAATCTGGCGGTGACCCCGGACC TGCAATTTGCGA - agged AGGAGTTCTT AGCGGTCTGCACCAGAATTTCCAGACGGCCGCAGCCGAGGGCAAAGTCGTCACTTGTTT Nostoc GTTGATCCJ-GAGCCTGATTATTGAATGCTTTGCTATTGCGGCGTACAACATTTACATTC CGGTCGCCGAT pvinct: £ox^sne GACTTTGCGCGTAAAATCACGGAAGGTGTTGTCAAAGAGGAGTATTCCCACCTGAATTTC GGTGAAGTGT

GGTTGAAGGAACATTTTGCGGAATCTAAAGCCGAATTGGAACTGGCAAATCGCCAGAACC TGCCGATCGT

acta . TTGGAAGATGCTGAACCAAGTGGAAGGTGATGCACATACGATGGCGATGGAGAAGGACGC ATTGGTTGAG

GACTTTATGATTCAGTATGGCGAAGCACTGTCCAATATCGGTTTCAGCACCCGTGATATC ATGCGTCTGA GCGCCTATGGCCTGATCGGTGCCTAA

codon- ATGGAGTGGAAACCAAAACCGAAACTGCCTCAGCTGCTGGATGACCACTTCGGTCTGCAC GGCCTGGTTT

TCCGTCGTACCTTCGCTATCCGTTCTTACGAAGTCGGCCCTGATCGCTCCACCTCCATCC TGGCGGTAAT

optiini zed

GAACCACATGCAGGAAGCAACTCTGAACCATGCGAAAAGCGTAGGTATCCTGGGCGATGG TTTCGGCACT

Umbel 1 ul I a ACTCTGGAGATGTCCAAACGTGATCTGATGTGGGTTGTTCGCCGTACCCATGTCGCGGTT GAACGCTACC call fo∑Tiica CGACCTGGGGCGATACGGTTGAAGTGGAATGCTGGATCGGCGCGTCCGGCAACAACGGCA TGCGTCGCGA £utB _m (without TTTCCTGGTTCGCGATTGTAAGACGGGCGAGATTCTGACCCGTTGCACGTCCCTGAGCGT TCTGATGAAT leader ACCCGTACCCGTCGTCTGAGC&CCATCCCGG&CG&&GTTCGCGG TG&&ATTGGCCCGGC&T ^, C&TCG&T&

ACGTTGCAGTAAAAGACGATGAAATCAAGAAACTGCAGAAACTGAATGACTCTACCGCGG ACTACATCCA

sequence) - GGGTGGTCTGACCCCGCGCTGG&ACGACCTGGACGTGAACCAGCACGTCAAC& ;ACCTG&AATACGTAGCT

TGGGTATTCGAAACGGTCCCGGATTCTATCTTCGAATCTCACCACATCAGCTCCTTCACC CTGGAATACC GTCGTGAGTGTACCCGTGACTCCGTTCTGCGCTCTCTGACCACGGTATCCGGCGGTAGCT CTGAAGCCGG TCTGGTTTGCGATCACCTGCTGCAGCTGGAAGGCGGCAGCGAGGTTCTGCGTGCTCGTAC TGAGTGGCGT CCGAAGCTGACTGACTCTTTCCGCGGCATCTCTGTTATCCCGGCAGAGCCTCGTGTGTAA

codon- ATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCACACGTTACATTTCGTCGAATTT GATCCGGCGA optiiffiized E. ACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCC GTAAGCGTAA

AACTGAACATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCTACAA ATGCGTGCCG

coli. entD. GCCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCAC TGCGGTACTA

CCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTG TCCAGACGGC ACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAGCGTCTGGCGGACTGTGG TCTGGCGTTC AGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATC CAAACCGATG CGGGCTTCCTGGATTATCAAATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTG AGAATGAGAT GTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACCCTGTGCCAGCACGACTG A

plasiaid TAGAAAAACTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCAGGATTATCAATA CCATATTTTT pAQ4 : : P ( cqpcB) GAAAAAGCCGTTTCTGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAA GATCCTGGTA

TCGGTCTGCGATTCCGACTCGTCCAACATCAATACAACCTATTAATTTCCCCTCGTCAAA AATAAGGTTA TCAAGTGAGAAATCACCATGAGTGACGACTGAATCCGGTGAGAATGGCAAAAGTTTATGC ATTTCTTTCC

Nhistag adm(N AGACTTGrTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAAC CGTTATTCAT pu) -ExaC TCGTGATTGCGCCTGAGCGAGGCGAAATACGCGATCGCTGTTAAAAGGACAATTACAAAC AGGAATCGAG

TGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATAT TCTTCTAATA CCTGGAaCGCTGTTTTTCCGGGGATCGCAGTGGTGAGTAACCATGCATCATCAGGAGTAC GGATAAAATG CTTGATGGTCGGAAGTGGCATAAATTCCGTCAGCCAGTTTAGTCTGACCATCTCATCTGT AACATCATTG GCAACGCTACCTTTGCCATGTTTCAGAAACAACTCTGGCGCATCGGGCTTCCCATACAAG CGATAGATTG TCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATACCCATATAAATCAGCATCCA TGTTGGAATT

TATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAA CAAATAGGGGTCA GTGTTACAACCAATTAACCAATTCTGAACATTATCGCGAGCCCATTTATACCTGAATATG GCTCATAACA CCCCTTGTTTGCCTGGCGGCAGTAGCGCGGTGGTCCCACCTGACCCCATGCCGAACTCAG AAGTGAAACG CCGTAGCGCCGATGGTAGTGTGGGGACTCCCCATGCGAGAGTAGGGAACTGCCAGGCATC AAATAAAACG AAAGGCTCAGTCGAAAGACTGGGCCTTTCGCCCGGGCTAATTAGGGGGTGTCGCCCTTTA CACGTACTTA GTCGCTGAAGGCCTCACTGGCCCCTGCAGGGATGGTGGAATGCTGGTTATCTGGTGGGGA TTAAGTGGTG TTTTACTAAAGCTTGAACAACTCAAGAAAGATTATATTCGCAATAACTGCCAATAATCCC AGCATCTTGA GAAAATCCAGCAAACCGGGGGCAAAACACCAGCAAGAAGCCAGCAGACTATCACCAAATC CCCAGCGTAC AGCTAGAAATAACTGAGCAGTTGTATTCAATTACCTTCTGGTCAAGCCGAGGAAATTTCC CCACACCTTA TACACCTCTGGAAGGTTTTTTTGACGAAGCGCAAAATATCCACAATCGGCTGGGGACTTC TTCTGTCAGA AAArGGCAGAAATTTTTGAATGTGTTGGCGATCGCCCTCATCAATGATTATTAGAGAACT TTTGTCCCTG ATGTTGGGAaTACTCTTGATGACAATTGTGATTGCTCAAAGAAGAAAGAAATTTGGAGTA AATCTCTAAA AGGGGACTGAAATATTTGTATGGTCAGCATGACCACTGAAATGGAGAGAAGTCTAAGACA GTAGATGTCT TAGATATAAGCCTCATTAGAAGCCATGCCATAAAACAGATTTTGTGGATGAAACAACTTG AAATAGTTCA GTTGTAGACCATGTTATAAACATTTATTCTTAACACAGTGACACATTAATGACTCATATA TCCGTCCAAA AAAAACTAAAATGTTTGTAAATTTAGTTTTGCGGCCGCGTCGACTTCGTTATAAAATAAA CTTAACAAAT CTATACCCACCTGTAGAGAAGAGTCCCTGAATATCAAAATGGTGGGATAAAAAGCTCAAA AAGGAAAGTA GGCTGTGGTrCCCTAGGCAACAGTCTTCCCTACCCCACTGGAAACTAAAAAAACGAGAAA AGTTCGCACC GAACATCAATTGCATAATTTTAGCCCTAAAACATAAGCTGAACGAAACTGGTTGTCTTCC CTTCCCAATC CAGGACAATCTGAGAATCCCCTGCAACATTACTTAACAAAAAAGCAGGAATAAAATTAAC AAGATGTAAC AGACATAAGTCCCATCACCGTTGTATAAAGTTAACTGTGGGATTGCAAAAGCATTCAAGC CTAGGCGCTG AGCTGTTTGAGCATCCCGGTGGCCCTTGTCGCTGCCTCCGTGTTTCTCCCTGGATTTATT TAGGTAATAT CTCTCATAAATCCCCGGGTAGTTAACGAAAGTTAATGGAGATCAGTAACAATAACTCTAG GGTCATTACT TTGGACTCCCTCAGTTTATCCGGGGGAATTGTGTTTAAGAAAATCCCAACTCATAAAGTC AAGTAGGAGA TTAATCATArGCACCATCACCACCATCATGGAGGCGGACAGCAACTGACCGATCAAAGCA AAGAACTGGA CTTCAaGAGCGAGACGTACAAAGACGCCTATAGCCGCATTAACGCGATCGTCATTGAAGG CGAACAAGAG GCGCATGAAAACTACATCACCCTGGCGCAGCTGCTGCCTGAGAGCCACGACGAACTGATT CGCCTGAGCA AAATGGAGAGCCGTCACAAGAAAGGTTTTGAGGCGTGTGGCCGCAATCTGGCGGTGACCC CGGACCTGCA ATTTGCGAAGGAGTTCTTTAGCGGTCTGCACCAGAATTTCCAGACGGCCGCAGCCGAGGG CAAAGTCGTC ACTTGTTTGTTGATCCAGAGCCTGATTATTGAATGCTTTGCTATTGCGGCGTACAACATT TACATTCCGG TCGCCGATGACTTTGCGCGTAAAATCACGGAAGGTGTTGTCAAAGAGGAGTATTCCCACC TGAATTTCGG TGAAGTGTGGTTGAAGGAACATTTTGCGGAATCTAAAGCCGAATTGGAACTGGCAAATCG CCAGAACCTG CCGATCGTTTGGAAGATGCTGAACCAAGTGGAAGGTGATGCACATACGATGGCGATGGAG AAGGACGCAT TGGTTGAGGACTTTATGATTCAGTATGGCGAAGCACTGTCCAATATCGGTTTCAGCACCC GTGATATCAT GCGTCTGAGCGCCTATGGCCTGATCGGTGCCTAAGAGCTCCTCGAGGAATTCGGTTTTCC GTCCTGTCTT GATTTTCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGCATTTGTTTTTGTTTATTGC AAAAACAAAA AATATTGTTACAAATTTTTACAGGCTATTAAGCCTACCGTCATAAATAATTTGCCATTTA CTAGTTTTAA TTAACGTGCTATAATTATACTAATTTTATAAGGAGGAAAAAATATGGGCATTTTTAGTAT TTTTGTAATC AGCACAGTTCATTATCAACCAAACAAAAAATAAGTGGTTATAATGAATCGTTAATAAGCA AAATTCATAT

AaCCAaATTAAAGAGGGTTATAATGAACGAGAAAAATATAAAACACAGTCAAAACTTTAT TACTTCAAAA CATAATATAGATAAAATAATGACAAATATAAGATTAAATGAACATGATAATATCTTTGAA ATCGGCTCAG GAAAAGGCCATTTTACCCTTGAATTAGTAAAGAGGTGTAATTTCGTAACTGCCATTGAAA TAGACCATAA ATTATGCAAAACTACAGAAAATAAACTTGTTGATCACGATAATTTCCAAGTTTTAAACAA GGATATATTG CAGTTTAAATTTCCTAAAAACCAATCCTATAAAATATATGGTAATATACCTTATAACATA AGTACGGATA TAATACGCAAAATTGTTTTTGATAGTATAGCTAATGAGATTTATTTAATCGTGGAATACG GGTTTGCTAA ftAGATTATTA¾ATACA&AACGCTCATTGGCATTACTTTTAATGGCAGAAGTTGA TATTTCTATATT&AGT ATGGTTCCA&G&G¾ATATTTTCATCCT¾A&CCT¾A&GTG¾ ATAGCTC&CTT&TCAGATT¾AGT&G¾A&A& AATCAAGAATATCACACAAAGATAAACAAAAGTATAATTATTTCGTTATGAAATGGGTTA ACAAAGAATA CA&GAAAATATTTACAAAAAATCAATTT&ACAATTCCTTAAAACATGCAGGA ATTGACGATTTAAACAAT ATTAGCTTTGAACAATTCTTATCTCTTTTCAATAGCTATAAATTATTTAATAAGTAAGTT AAGGGATGCA TAAACTGCATCCCTTAACTTGTTTTTCGTGTGCCTATTTTTTGTGGCGCGCCCAGTTTCC TTTACTGGCC CTAAaGTCGCTGTGGCTAGGGTTCCGAAGGGGCATTATTGGCTCGCGGCTTTACAACCTT GATAAGGAGA

CGAAATGGTTGAGCCGGCCTCGATACACTCAATTAACTACTAATAGCTTCAATAAAT TTTGGGACGATTG AAGCTATTTTTTTGAAAATCAACTCTTAATATCTCCTGTCTCAAAAGAGTTAATTGCTAA ACAAAAGCCA GTTTCAGCGAAAAATCTAGAGTTTTATAGGTTCGTTCTCAGTACAGGACA AAAGTTTGAAAAGGATAGA GGGAGAGGGTTTGATGGAAATAAGCACAAATCAATCAAGCCCTCATGAATCAGATTAGCG AAATTCGCCG CCAATTGCGACCTCATCTCGGATGGCATGGAGCCAGACTGTCATTTATCGCCCTCTTCCT GGTGGCACTG TTCCGAGCAAAAACCGTCAATCTCGCCAAACTCGCCACCGTCTGGGGAGGCAATGCAGCA GAAGAGTCTA ATTACAAACGCATGCAGCGATTCTTTCAGTCCTTTGACGTCAACATGGACAAAATCGCCA GGATGGTAAT GAATATCGCGGCTATCCCGCAACCTTGGGTCTTAAGCATCGACCGCACCAACGGCCGGCC TACATGGCCC GTCAATCGAAGGGCGACACAAAATTTATTCTAAATGCATAATAAATACTGATAACATCTT ATAGTTTGTA TTATATTTTGTATTATCGTTGACATGTATAATTTTGATATCAAAAACTGATTTTCCCTTT ATTATTTTCG AGATTTATTTTCTTAATTCTCTTTAACAAACTAGAAATATTGTATATACAAAAAATCATA AATAATAGAT GSATAGTTTSATTATAGGTGTTCATCAATCGAA AAGCAACGTATCTTATTTAAAGTGCGTTGCTTTTTT CTCATTTATAAGGTTAAATAATTCTCATATATCAAGCAAAGTGACAGGCGCCCTTAAATA TTCTGACAAA

GATTACTCGTTATCAGAACCGCCCAGGGGGCCCGAGCTTAAGACTGGCCGTCGTTTT ACAACACAGAAAG AGTTTGTAGAAACGCAAAAAGGCCATCCGTCAGGGGCCTTCTGCTTAGTTTGATGCCTGG CAGTTCCCTA CTCTCGCCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGA GCGGTATCAG CTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAACA TGTGAGCAAA AGGCCAGCA&AAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATA GGCTCCGCCCCCCT GACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAA AGATACCAGG CGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGAT ACCTGTCCGC CTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTC GGTGTAGGTC GTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTA TCCGGTAACT ATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTA ACAGGATTAG CAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGGCTAACTACGGCTA CACTAGAAGA ACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGC TCTTGATCCG GCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCA GAAAAAAAGG ATCTCAAGSAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGACGCGCG CGTAACTCAC GTTAAGGGATTTTGGTCATGAGCTTGCGCCGTCCCGTCAAGTCAGCGTAATGCTCTGCTT T

plasittid. AAAAGCAGAGCATTACGCTGACTTGACGGGACGGCGCAAGCTCATGACCAAAATCCCTTA ACGTGAGTTA pAQ3: :P(nirQ7 CGCGCGCGTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAG ATCCTTTTTT

TCrGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATCAA ) -£abB _n ~carB~ GAGCTACCAACTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACT GTTCTTCTAG enfcD-SpecR. TGTAGCCGTAGTTAGCCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC TGCTAATCCT

GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG GATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACA CCGA&CTGAGATACCTACAGCGTGAGCTATGAGAAAGCGCCACGCTTCCCGAAGGG AGAAAGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAA CGCCTGGTAT

GGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCT GGCCTTTTGCTCA CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTG AGCTGATACC GCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCATCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT GTTGTAAA&CGACGGCCAGTCTTAAGCTCGGGCCCCCTGGGCGGTTCTGATAACGA GTAATCGTTAATCC

AATATTrAAGGGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTTATAA ATGAGAAAAAAGC AACGCACTTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTATAATTAAACTAT TCATCTATTA TTTATGATTrTTTGTATATACAATATTTCTAGTTTGTTAAAGAGAATTAAGAAAATAAAT CTCGAAAATA ATAAAGGGAAAATCAGTTTTTGATATCAAAATTATACATGTCAACGATAATACAAAATAT AATACAAACT ATAAGATGTTATCAGTATTTATTATGCATTTAGAATAAATTTTGTGTCGCCCTTCGCTGA ACCTGCAGGC GAGCATTTCAACGATGATGAATGGGACGGCGAACCCACTGAACCCGTCGCCATTGACCCA GAACCGCGCA AAGAACGGGAAAAAATTGATCTCGATCTGGAGGATGAACCAGAGGAAAACCGCAAACCGC AAAAAATCAA AGTGA&GTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTCAAACCACAACTT TTTGGGATGCTGAT GGTAaACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG AAGCCGAACTACGCACCATCTGGGGGAAACCCGATACCCGTAAATCGTTCCTGACCGGAC TCGCGGAAAA AGGCTACGGTGACACCCAACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAAGTGA TGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC

AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCA AACCGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG ATGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCTTG TAGCAATTGC TACTAAAAACTGCGATCGCTGCTGAAATGAGCTGGAATTTTGTCCCTCTCAGCTCAAAAA GTATCAATGA TTACTTAaTGTTTGTTCTGCGCAAACTTCTTGCAGAACATGCATGATTTACAAAAAGTTG TAGTTTCTGT TACCAATTGCGAATCGAGAACTGCCTAATCTGCCGAGTATGCGATCCTTTAGCAGGAGGA AAACCATATG GAGTGGAAaCCAAAACCGAAACTGCCTCAGCTGCTGGATGACCACTTCGGTCTGCACGGC CTGGTTTTCC GTCGTACCTTCGCTATCCGTTCTTACGAAGTCGGCCCTGATCGCTCCACCTCCATCCTGG CGGTAATGAA CCACATGCAGGAAGCAACTCTGAACCATGCGAAAAGCGTAGGTATCCTGGGCGATGGTTT CGGCACTACT CTGGAGATGTCCAAACGTGATCTGATGTGGGTTGTTCGCCGTACCCATGTCGCGGTTGAA CGCTACCCGA CCTGGGGCGATACGGTTGAAGTGGAATGCTGGATCGGCGCGTCCGGCAACAACGGCATGC GTCGCGATTT

\&T&CC

.TTCGCGGTGAAATTGGCCCGGCATTCATCGATAACG ¾AGifiAACTGCAGAAACTGAATGACTCTACCGCGGACTACATCC-¾GGG TGGTCTGACCCCGCGCTGGAACGACCTGGACGTGAACCAGCACGTCAACAACCTGAAATA CGTAGCTTGG GTATTCGAAACGGTCCCGGATTCTATCTTCGAATCTCACCACATCAGCTCCTTCACCCTG GAATACCGTC

GGTTTGCGATCACCTGCTGCAGCTGGAAGGCGGCAGCGAGGTTCTGCGTGCTCGTAC TGAGTGGCGTCCG AAGCTGACTGACTCTTTCCGCGGCATCTCTGTTATCCCGGC-feGiAGCCTCGTGTGTAA GAGCTCGAGGAGG TTTTTACAA GACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCGACGACGAGCA GTCGACCCGCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACC GTTGCCCGCC GTGGTCGACGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTC ACCGGCTACG GTGACCGCCCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCGGGCGCA CCGTGACGCG TCTGCTGCCGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCAAGCGGT CGCCGCGGCC CTGCGCCACJ-ACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTT CGCGAGTCCCG ATTACCTGAOKTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGCAGCa C^CGCACC GGTCAGCCGGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGC CGAATACCTC GACCTCGCAGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGAC CATCACCCCG AGGTCGACGACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCA TCGCCGTCAC

C -GCGCCTCGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATGT ACaCCGAGG CGATGGTGGCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCA ACGTCAACTT CATGCCGCTCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGG AACCAGTTAC TTCGTACCGGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACC GAACTCGGCC TGGTTCCGCGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGG TCACGCAGGG CGCCGACGAACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGG CGGACGCGTG ATCACCGGATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTCGACATC ACCCTGGGCG

CacacaTCG CGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGATCGTGCGGCC ACCGGTGATCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCACCGACAA GCCCTACCCG CGTGGCGAACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGCCCCGAG GTCACCGCGA GCGTCTTCGACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCG ACCACCTGGT GTACGTGGACCGTCGCAAC^CGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGCC ^CCTGGAG GCGGTGTTCTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGCGAGCGC AGTTTCCTTC TGGCCGTGGTGGTCCCGiACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAG GCCGCGCTGGC CGACTCGCTGCAGCGCA GAGACCGAGCCGTTCAGCGCCGCCM

AaGACCGCTACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGCAGG CCAACCAGTTGCG

GGCaCCGGGAGCGAGGTGGCATCCGACGCCCaCTTCACCGACCTGGGCGGGGATTCC CTGTCGGCGCTGA CACTTTCGAACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGA ACCCGGCCAC CAACCTCGCCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCC GAGTTTCACC ACCGTGCACGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGACAAGTTC ATCGACGCCG AAACGCTCCGGGCCGCACCGGGTCTGCCCAAGGTCACC-ACCGiAGCCACGGACGGTGTT GCTCTCGGGCGC CAACGGCTGGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGG CGGCACCCTC ATCACGATCGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTAC GACACCGATC CCGAGTTGTCCCGCCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTG ACATCGGCGA CCCGAATCTGGGCCTCACACCCGAGATCTGGCACCGGCTCGCCGCCGAGGTCGACCTGGT GGTGCATCCG

SACGTCGTGGGCACGGCCGAGG

¾AGCCCGTCACGTACCTGTCCACCGTGTCGGTGGCCATGGG

GCCAACGGCTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCCCAC GATCTGTGCGGGC TGCCCGTGGC¾3ACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCGGTCA GGTCAACGTGCC AGACATGTTCaCGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCGGTCGTT CTACATCGGA GACGGTGAGCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCG GTCACGACGC TCGGCGCGCAGO.GCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACG GGATCTCCCT GGATGTGTTCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTA CGACGACTGG GTGCGTCGGTTCGAGACCGCGTTGiACCGCGCTTCCCGAGAAGCGCCGCGC-ACAGACCG TACTGCCGCTGC TGCACGCGTTCCGCGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGGAGGTGT TCCACGCCGC GGTGCGCACCGCGAAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCTGATCGA CAAGTACATA CGCGATCTGCGTGAGTTCGGTCTGATCTGAGGTACCCaC^GGAGGTTTTTAC^TGAAAAC GACCCACA CCaGCTTACCaTTTGCCGGCCACACGTTACATTTCGTCGAATTTGATCCGGCGAACTTTT GTGAACAAGA CCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCCGTAAGCGTAAAACTGA ACATCTGGCC GGTCGCATTGCGGCJ-GTGTATGCCCTGCGCGAGTACGGCTAaUU-TGCGTGCCGGCCAT TGGTGAACTGC

GTCTCGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTGTCCAGACGGCACG CGAGCTGACGGAC

TGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATCCAAACCGATGCGG GCTTCCTGGATTA TCAAATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTGAGAATGAGATGTTTGC CGTCCATTGG CAGATTAAAGAGAAAATCGTTATCaCCCTGTGCO-GCACGACTGAGAATTCGGTTTTCCG TCCTGTCTTG ATTTTCAAGaAAACAATGCCTCCGATTTCTAATCGGAGGCATTTGTTTTTGTTTATTGCA AAAACAAAAA ATATTGTTACa^TTTTTACAGGCTATTAAGCCTACCGTCATAAATAATTTGCCATTTACT AGTTTTTAA TTAACC kGAACCTTGACCGAACGCAGCGGTGGTAACGGCGCAGTGGCGGTTTTCATGGCTTGTTAT GACT GTTTTTTTGGGGTACAGTCTATGCCTCGGGCATCCAAGCAGCAAGCGCGTTACGCCGTGG GTCGATGTTT GATGTTATGGAGCAGCAACGATGTTACGCAGCAGGGCAGTCGCCCTAAAACAAAGTTAAA CATCATGAGG GAAGCGGTGATCGCCGAAGTATCGACTCAACTATO.GAGGTAGTTGGCGTCATCGAGCGC CATCTCGAAC CGACGTTGCTGGCCGTACaTTTGTACGGCTCCGC^TGGATGGCGGCCTGAAGCCACACAG TGATATTGA TTTGCTGGTTACGGTGACCGTAAGGCTTGATGAAACAACGCGGCGAGCTTTGATCAACGA CCTTTTGGAA ACTTCGGCTTCCCCTGGAGAGAGCGAGATTCTCCGCGCTGTAGA¾GTCACCATTGTTGT GCACGACGACA TCATTCCGTGGCGTTATCCAGCTAAGCGCGAACTGCAATTTGGAGAATGGCAGCGCAATG ACATTCTTGC AGGTATCTTCGAGCCAGCCACGATCGACATTGATCTGGCTATCTTGCTGACAAAAGCAAG AGAACATAGC GTTGCCTTGGTAGGTCCAGCGGCGGAGGAACTCTTTGATCCGGTTCCTGAACAGGATCTA TTTGAGGCGC TAAATGAAACCTTAACGCTATGGAACTCGCCGCCCGACTGGGCTGGCGATGAGCGAAATG TAGTGCTTAC GTTGTCCCGCATTTGGTACAGCGCAGTAACCGGCAAAATCGCGCCGAAGGATGTCGCTGC CGACTGGGCA ATGGAGCGCCTGCCGGCCCAGTATCAGCCCGTCATACTTGAAGCTAGACAGGCTTATCTT GGACAAGAAG AAGATCGCTTGGCCTCGCGCGCAGATCAGTTGGAAGAATTTGTCCACTACGTGAAAGGCG AGATCACCAA GGTAGTCGG LAAATAATGTCTAACAATTCGTTCAAGCCGACGCCGCTTCGCGGCGCGGCTTAACTCAAG C GTTAGATGCACTAAGCACATAATTGCTCACAGCCAAACTATCAGGTCAAGTCTGCTTTTA TTATTTTTAA GCGTGCATAATAAGCCCTACACAAATTGGGAGATATATCATGAGGCGCGCCACGAGAAAG AGTTATGACA AATTAAAATTCTGACTCTTAGATTATTTCCAGAGAGGCTGATTTTCCCAATCTTTGGGAA AGCCTAAGTT TTTAGATTCTATTTCTGGATACATCTCAAAAGTTCTTTTTAAATGCTGTGCAAAATTATG CTCTGGTTTA ATTCTGTCTAAGAGATACTGAATACAACATAAGCCAGTGAAAATTTTACGGCTGTTTCTT TGATTAATAT CCTCCAATACTTCTCTAGAGAGCCATTTTCCTTTTAACCTATCAGGCAATTTAGGTGATT CTCCTAGCTG TATATTCCAGAGCCTTGAATGATGAGCGCAAATATTTCTAATATGCGACAAAGACCGTAA CCAAGATATA AAAAACTTGTTAGGTAATTGGAAATGAGTATGTATTTTTTGTCGTGTCTTAGATGGTAAT AAATTTGTGT ACATTCTAGATAACTGCCCAAAGGCGATTATCTCCAAAGCCATATATGACGGCGGTAGTA GAGGATTTGT GTACTTGTTTCGATAATGCCCGATAAATTCTTCTACTTTTTTAGATTGGCAATATTGAGT AATCGAATCG ATTAATTCTTGATGCTTCCCAGTGTCATAAAATAAACTTTTATTCAGATACCAATGAGGA TCATAATCAT GGGAGTAGTGATAAATCATTTGAGTTCTGACTGCTACTTCTATCGACTCCGTAGCATTAA AAATAAGCAT TCTCAAGGATTTATCAAACTTGTATAGATTTGGCCGGCCCGTCAAAAGGGCGACACCCCA TAATTAGCCC GGGCGAAAGGCCCAGTCTTTCGACTGAGCCTTTCGTTTTATTTGATGCCTGGCAGTTCCC TACTCTCGCA TGGGGAGTCCCCACACTACCATCGGCGCTACGGCGTTTCACTTCTGAGTTCGGCATGGGG TCAGGTGGGA CCACCGCGCTACTGCCGCCAGGCAAACAAGGGGTGTTATGAGCCATATTCAGGTATAAAT GGGCTCGCGA TAATGTTCAGAATTGGTTAATTGGTTGTAACACTGACCCCTATTTGTTTATTTTTCTAAA TACATTCAAA TATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTTCAATAATATTGAAAAAGGAA GAATATGAGT ATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGGCATTTTGCCTTCCTGTTTTT GCTCACCCAG AAACGCTGGrGAAAGTAAAAGATGCTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCG AACTGGATCT CAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAACGTTTTCCAATGATGAGCAC TTTTAAAGTT CTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGCAAGAGCAACTCGGTCGCCGC ATACACTATT CTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAAGCATCTTACGGATGGCATGA CAGTAAGAGA ATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCGGCCAACTTACTTCTGACAAC GATCGGAGGA

AGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCACGATGCCTGTAGCGATGG CAACAACGTTGCG CAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGGCAACAATTAATAGACTGGAT GGAGGCGGAT AAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTGGCTGGTTTATTGCTGATAAA TCCGGAGCCG GTGAGCGTGGTTCTCGCGGTATCATCGCAGCGCTGGGGCCAGATGGTAAGCCCTCCCGTA TCGTAGTTAT CTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAATAGACAGATCGCTGAGATAGG TGCCTCACTG ATTAAGCATTGGT

carboxylic ATGACCAGCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCGACGACGAG CAGTCGACCC

GCCGCATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACCGTTGCCCG CCGTGGTCGA CGCGGCGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTCACCGGCTA CGGTGACCGC

reductase CCGGCGCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCGGGCGCACCGTGACG CGTCTGCTGC amp! f ied CGCGGTTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCAAGCGGTCGCCGCGG CCCTGCGCCA from CAACTTCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTTCGCGAGTCC CGATTACCTG

ACGCTGGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGCAGCACAACGCA CCGGTCAGCC

MycobscteTiis

GGCTCGCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGCCGAATACC TCGACCTCGC

smsgsi tis . AGTCGAATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGACCATCACCC CGAGGTCGAC

GACCACCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCATCGCCGTC ACCACCCTGG ACGCGATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTACACCGCCGACCATG ATCAGCGCCT CGCGATGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATGTACACCGA GGCGATGGTG GCGCGGCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCAACGTCAAC TTCATGCCGC TCAACCACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGGAACCAGTT ACTTCGTACC GGAATCCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACCGAACTCGG CCTGGTTCCG CGCGTCGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGGTCACGCAG GGCGCCGACG AACTGACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGGCGGACGCG TGATCACCGG ATTCGTCAGCACCGCACCGCTGGCCGCGGAGATGAGGGCGTTCCTCGACATCACCCTGGG CGCACACATC GTCGACGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGATCGTGCGG CCACCGGTGA TCGACTACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCACCGACAAGCCCTACC CGCGTGGCGA ACTGCTGGTCAGGTCGCAAACGCTGACTCCCGGGTACTACAAGCGCCCCGAGGTCACCGC GAGCGTCTTC GACCGGGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCGACCACCTG GTGTACGTGG ACCGTCGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGCCAACCTGG AGGCGGTGTT CTCCGGCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGCGAGCGCAGTTTCCT TCTGGCCGTG GTGGTCCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAGGCCGCGCTG GCCGACTCGC TGCAGCGCACCGCACGCGACGCCGAACTGCAATCCTACGAGGTGCCGGCCGATTTCATCG TCGAGACCGA GCCGTTCAGCGCCGCCAACGGGCTGCTGTCGGGTGTCGGAAAACTGCTGCGGCCCAACCT CAAAGACCGC TACGGGCAGCGCCTGGAGCAGATGTACGCCGATATCGCGGCCACGCAGGCCAACCAGTTG CGCGAACTGC GGCGCGCGGCCGCCACACAACCGGTGATCGACACCCTCACCCAGGCCGCTGCCACGATCC TCGGCACCGG GAGCGAGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGATTCCCTGTCGGCGCT GACACTTTCG AACCTGCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGAACCCGGCC ACCAACCTCG CCCAACTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCCGAGTTTCA CCACCGTGCA CGGCGCGGACGCCACCGAGATCCGGGCGAGTGAGCTGACCCTGGACAAGTTCATCGACGC CGAAACGCTC CGGGCCGCACCGGGTCTGCCCAAGGTCACCACCGAGCCACGGACGGTGTTGCTCTCGGGC GCCAACGGCT GGCTGGGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGGCGGCACCC TCATCACGAT CGTGCGGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTACGACACCGA TCCCGAGTTG TCCCGCCGCTTCGCCG&GCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTG& ;C&TCGGCGACCCG&ATC TGGGCCTCACACCCG&G&TCTGGCACCGGCTCGCCGCCG&GGTCG&am p;CCTGGTGGTGC&TCCGGCAGCGCT GGTCAACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTCGTGGGCACGGCCGA GGTGATCAAG CTGGCCCTCACCGAACGG&TCAAGCCCGTC&CGT&CCTGTCC&C CGTGTCGGTGGCCATGGGGATCCCCG ACTTCGAGGAGGACGGCGACATCCGGACCGTGAGCCCGGTGCGCCCGCTCGACGGCGGAT ACGCCAACGG CTACGGCAACAGCAAGTGGGCCGGCGAGGTGCTGCTGCGGGAGGCCCACGATCTGTGCGG GCTGCCCGTG GCGACGTTCCGCTCGGACATGATCCTGGCGCATCCGCGCTACCGCGGTCAGGTCAACGTG CCAGACATGT TCACGCGACTCCTGTTGAGCCTCTTGATCACCGGCGTCGCGCCGCGGTCGTTCTACATCG GAGACGGTGA GCGCCCGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCGGTCACGAC GCTCGGCGCG CAGCAGCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACGGGATCTCC CTGGATGTGT TCGTGGACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTACGACGACT GGGTGCGTCG GTTCGAGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAGACCGTACTGCCGCT GCTGCACGCG TTCCGCGCrCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGGAGGTGTTCCACGCC GCGGTGCGCA CCGCGAaGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCTGATCGACAAGTACA TACGCGATCT GCGTGAGTTCGGTCTGATCTGA

codon- ATGCACCATCACCACCATCATGGAGGCGGACAGCAACTGACCGATCAAAGCAAAGAACTG GACTTCAAGA optiiffiized GCGAGACGTACAAAGACGCCTATAGCCGCATTAACGCGATCGTCATTGAAGGCGAACAAG AGGCGCATGA

AAACTACATCACCCTGGCGCAGCTGCTGCCTGAGAGCCACGACGAACTGATTCGCCTGAG C&AAATGGAG hexahisfcidine AGCCGTCACAAGAAAGGTTTTGAGGCGTGTGGCCGCAATCTGGCGGTGACCCCGGACCTG CAATTTGCGA

-tagged AGGAGTTCTTTAGCGGTCTGCACCAG&ATTTCCAGACGGCCGCAGCCGAGGGCAAA GTCGTCACTTGTTT

Nostoc GTTGATCCAGAGCCTGATTATTGAATGCTTTGCTATTGCGGCGTACAACATTTACATTCC GGTCGCCGAT pvmctiforme GACTrTGCGCGTAAAATCACGGAAGGTGTTGTCAAAGAGGAGTATTCCCACCTGAATTTC GGTGAAGTGT

GGTTGAaGGAACATTTTGCGGAATCTAAAGCCGAATTGGAACTGGCAAATCGCCAGAACC TGCCGATCGT adka. TTGGAAGATGCTGAACCAAGTGGAAGGTGATGCACATACGATGGCGATGGAGAAGGACGC ATTGGTTGAG

GACTTTATGATTCAGTATGGCGAAGCACTGTCCAATATCGGTTTCAGCACCCGTGATATC ATGCGTCTGA GCGCCTATGGCCTGATCGGTGCCTAA

eodon- ATGAAAACGACCCACACCAGCTTACCATTTGCCGGCCACACGTTACATTTCGTCG& ATTTGATCCGGCGA optiittized E, ACTTTTGTGAACAAGACCTGTTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCC GTAAGCGTAA

AACTGA&CATCTGGCCGGTCGCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCT AC&AATGCGTGCCG coll sntD. GCCATTGGTGAACTGCGTCAACCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCAC TGCGGTACTA

CCGCGTTGGCGGTTGTGTCTCGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTG TCCAGACGGC ACGCGAGCTGACGGACAACATCATTACCCCGGCAGAGCACGAGCGTCTGGCGGACTGTGG TCTGGCGTTC AGCCTGGCGCTGACCCTGGCATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATC CAAACCGATG CGGGCTTCCTGGATTATCAAATCATCAGCTGGAAC&AGC&ACAGGTTATCAT TCACCGTGAGAATGAGAT GTTTGCCGTCCATTGGCAGATTAAAGAGAAAATCGTTATCACCCTGTGCCAGCACGACTG A

plasmid AAA&GCAGAGCATTACGCTGACTTGACGGGACGGCGC&AGCTCATGACC&am p;AAATCCCTT&ACGTGAGTTA pAQ3 : : P { cpcB) CGCGCGCGTCGTTCCACTGAGCGTCAGACCCCGTAGAAAAGATCAAAGGATCTTCTTGAG ATCCTTTTTT

TCTGCGCGTAATCTGCTGCTTGCAAACAAAAAAACCACCGCTACCAGCGGTGGTTTGTTT GCCGGATC&A GAGCTACCAaCTCTTTTTCCGAAGGTAACTGGCTTCAGCAGAGCGCAGATACCAAATACT GTTCTTCTAG

Nhistag adm{N TGTAGCCGTAGTTAGCCCACCACTTCAAGAACTCTGTAGCACCGCCTACATACCTCGCTC TGCTAATCCT pu) -SpecR. GTTACCAGTGGCTGCTGCCAGTGGCGATAAGTCGTGTCTTACCGGGTTGGACTCAAGACG ATAGTTACCG

GATAAGGCGCAGCGGTCGGGCTGAACGGGGGGTTCGTGCACACAGCCCAGCTTGGAGCGA ACGACCTACA CCGAACTGAGATACCTACAGCGTGAGCTATGAG&AAGCGCCACGCTTCCCG& AGGGAGAAAGGCGGACAG GTATCCGGTAAGCGGCAGGGTCGGAACAGGAGAGCGCACGAGGGAGCTTCCAGGGGGAAA CGCCTGGTAT

GGAGCCTATGGAAAAACGCCAGCAACGCGGCCTTTTTACGGTTCCTGGCCTTTTGCT GGCCTTTTGCTCA CATGTTCTTTCCTGCGTTATCCCCTGATTCTGTGGATAACCGTATTACCGCCTTTGAGTG AGCTGATACC GCTCGCCGCAGCCGAACGACCGAGCGCAGCGAGTCAGTGAGCGAGGAAGCGGAAGGCGAG AGTAGGGAAC TGCCAGGCATCAAACTAAGCAGAAGGCCCCTGACGGATGGCCTTTTTGCGTTTCTACAAA CTCTTTCTGT GTTGTAAAACGACGGCCAGTCTT&AGCTCGGGCCCCCTGGGCGGTTCTGAT& ACGAGTAATCGTT&ATCC GCAAATAACGTAAAAACCCGCTTCGGCGGGTTTTTTTATGGGGGGAGTTTAGGGAAAGAG CATTTGTCAG AATATTTA&GGGCGCCTGTCACTTTGCTTGATATATGAGAATTATTTAACCTTATA AATGAG&AAAAAGC AACGCACTTTAAATAAGATACGTTGCTTTTTCGATTGATGAACACCTATAATTAAACTAT TCATCTATTA TTTATGATTTTTTGTATATACAATATTTCTAGTTTGTTAAAGAGAATTAAGAAAATAAAT CTCGAAAATA ATAAaGGGAAAATCAGTTTTTGATATCAAAATTATACATGTCAACGATAATACAAAATAT AATACAAACT ATAAGATGTTATCAGTATTTATTATGCATTTAGAATAAATTTTGTGTCGCCCTTCGCTGA ACCTGCAGGC GAGCATTTCAACGATGATGAATGGGACGGCGAACCCACTGAACCCGTCGCCATTGACCCA GAACCGCGCA AAGAACGGGAAAAAATTGATCTCGATCTGGAGGATGAACCAGAGGAAAACCGCAAACCGC AAAAAATCAA AGTGAAGTTAGCCGATGGGAAAGAGCGGGAACTCGCCCATACTC&AACCACAACTT TTTGGGATGCTGAT GGTAAACCCATTTCCGCCCAAGAATTTATCGAAAAGCTATTTGGCGACCTGCCCGACCTC TTCAAGGATG

A&GCCGA&CTACGCACCATCTGGGGGAAACCCGATACCCGT&AATCGT TCCTGACCGGACTCGCGGAAAA AGGCTACGGTGACACCCAACTGAAGGCGATCGCACGCATTGCCGAAGCGGAAAAAAGTGA TGTCTATGAT GTCCTGACTTGGGTTGCCTACAACACCAAACCCATTAGCAGAGAAGAGCGAGTAATTAAG CATCGAGATC TGATTTTCTCGAAGTACACCGGAAAGCAGCAAGAATTTTTAGATTTTGTCCTAGACCAAT ACATTCGAGA AGGAGTGGAGGAACTTGATCGGGGGAAACTGCCTACCCTCATCGAAATCAAATACCAAAC CGTTAATGAA GGTTTAGTGATCTTGGGTCAGGATATCGGTCAAGTATTCGCAGATTTTCAGGCGGATTTA TATACCGAAG ATGTGGCATAAAAAAGGACGGCGATCGCCGGGGGCGTTGCCTGCCTTGAGCGGCCGCGTC GACTTCGTTA TAAAATAAACTTAAC&AATCTATACCCACCTGTAGAG&AGAGTCCCTGAATA TCAAAATGGTGGGAT&AA AAGCTCAAAAAGGAAAGTAGGCTGTGGTTCCCTAGGCAACAGTCTTCCCTACCCCACTGG AAACTAAAAA AACGAGAAAAGTTCGCACCGAACATCAATTGCATAATTTTAGCCCTAAAACATAAGCTGA ACGAAACTGG TTGTCTTCCCTTCCCAATCCAGGACAATCTGAGAATCCCCTGCAACATTACTTAACAAAA AAGCAGGAAT AAAArTAACAAGATGTAACAGACATAAGTCCCATCACCGTTGTATAAAGTTAACTGTGGG ATTGCAAAAG CATTCAaGCCTAGGCGCTGAGCTGTTTGAGCATCCCGGTGGCCCTTGTCGCTGCCTCCGT GTTTCTCCCT GGATTTATTT&GGT&ATATCTCTC&T&A&TCCCCGGGT&a mp;GTT&ACG&A&GTT&ATGGAGATC&GTA&C& ;A TA&CTCTAGGGTCATTACTTTGGACTCCCTCAGTTTATCCGGGGG&ATTGTG TTT&AGA&A&TCCCA&CT CATAAAGTCAAGTAGGAGATTAATCATATGCACCATCACCACCATCATGGAGGCGGACAG CAACTGACCG ATCAAAGCAAAGAACTGGACTTCAAGAGCGAGACGTACAAAGACGCCTATAGCCGCATTA ACGCGATCGT CATTGAAGGCGAACAAGAGGCGCATGAAAACTACATCACCCTGGCGCAGCTGCTGCCTGA GAGCCACGAC GAACTGATTCGCCTGAGCAAAATGGAGAGCCGTCACAAGAAAGGTTTTGAGGCGTGTGGC CGCAATCTGG CGGTGACCCCGGACCTGCAATTTGCGAAGGAGTTCTTTAGCGGTCTGCACCAGAATTTCC AGACGGCCGC AGCCGAGGGCAAAGTCGTCACTTGTTTGTTGATCCAGAGCCTGATTATTGAATGCTTTGC TATTGCGGCG TACAACATTTACATTCCGGTCGCCGATGACTTTGCGCGTAAAATCACGGAAGGTGTTGTC AAAGAGGAGT ATTCCCACCTGAATTTCGGTGAAGTGTGGTTGAAGGAACATTTTGCGGAATCTAAAGCCG AATTGGAACT GGCAAATCGCCAGAACCTGCCGATCGTTTGGAAGATGCTGAACCAAGTGGAAGGTGATGC ACATACGATG GCGATGGAGAAGGACGCATTGGTTGAGGACTTTATGATTCAGTATGGCGAAGCACTGTCC AATATCGGTT TCAGCACCCGTGATATCATGCGTCTGAGCGCCTATGGCCTGATCGGTGCCTAAGAGCTCC TCGAGGAATT CGGTTTTCCGTCCTGTCTTGATTTTCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGC ATTTGTTTTT GTTTArTGCAAAAACAAAAAATATTGTTACAAATTTTTACAGGCTATTAAGCCTACCGTC ATAAATAATT TGCCATTTACTAGTTTTTAATTAACCAGAACCTTGACCGAACGCAGCGGTGGTAACGGCG CAGTGGCGGT TTTCATGGCTTGTTATGACTGTTTTTTTGGGGTACAGTCTATGCCTCGGGCATCCAAGCA GCAAGCGCGT TACGCCGTGGGTCGATGTTTGATGTTATGGAGCAGCAACGATGTTACGCAGCAGGGCAGT CGCCCTAAAA CAAAGTTAAACATCATGAGGGAAGCGGTGATCGCCGAAGTATCGACTCAACTATCAGAGG TAGTTGGCGT CATCGAGCGCCATCTCGAACCGACGTTGCTGGCCGTACATTTGTACGGCTCCGCAGTGGA TGGCGGCCTG AAGCCACACAGTGATATTGATTTGCTGGTTACGGTGACCGTAAGGCTTGATGAAACAACG CGGCGAGCTT TGATCAACGACCTTTTGGAAACTTCGGCTTCCCCTGGAGAGAGCGAGATTCTCCGCGCTG TAGAAGTCAC CATTGTTGTGCACGACGACATCATTCCGTGGCGTTATCCAGCTAAGCGCGAACTGCAATT TGGAGAATGG CAGCGCAATGACATTCTTGCAGGTATCTTCGAGCCAGCCACGATCGACATTGATCTGGCT ATCTTGCTGA CAAAAGCAAGAGAACATAGCGTTGCCTTGGTAGGTCCAGCGGCGGAGGAACTCTTTGATC CGGTTCCTGA ACAGGATCTATTTGAGGCGCTAAATGAAACCTTAACGCTATGGAACTCGCCGCCCGACTG GGCTGGCGAT GAGCGAAATGTAGTGCTTACGTTGTCCCGCATTTGGTACAGCGCAGTAACCGGCAAAATC GCGCCGAAGG ATGTCGCTGCCGACTGGGCAATGGAGCGCCTGCCGGCCCAGTATCAGCCCGTCATACTTG AAGCTAGACA GGCTTATCTTGGACAAGAAGAAGATCGCTTGGCCTCGCGCGCAGATCAGTTGGAAGAATT TGTCCACTAC GTGAAAGGCGAGATCACCAAGGTAGTCGGCAAATAATGTCTAACAATTCGTTCAAGCCGA CGCCGCTTCG CGGCGCGGCTTAACTCAAGCGTTAGATGCACTAAGCACATAATTGCTCACAGCCAAACTA TCAGGTCAAG TCTGCTTTTATTATTTTTAAGCGTGCATAATAAGCCCTACACAAATTGGGAGATATATCA TGAGGCGCGC CACGAGAAAGAGTTATGACAAATTAAAATTCTGACTCTTAGATTATTTCCAGAGAGGCTG ATTTTCCCAA TCTTTGGGAAAGCCTAAGTTTTTAGATTCTATTTCTGGATACATCTCAAAAGTTCTTTTT AAATGCTGTG CAAAATTATGCTCTGGTTTAATTCTGTCTAAGAGATACTGAATACAACATAAGCCAGTGA AAATTTTACG GCTGTTTCTTTGATTAATATCCTCCAATACTTCTCTAGAGAGCCATTTTCCTTTTAACCT ATCAGGCAAT TTAGGTGATTCTCCTAGCTGTATATTCCAGAGCCTTGAATGATGAGCGCAAATATTTCTA ATATGCGACA AAGACCGTAACCAAGATATAAAAAACTTGTTAGGTAATTGGAAATGAGTATGTATTTTTT GTCGTGTCTT AGATGGTAATAAATTTGTGTACATTCTAGATAACTGCCCAAAGGCGATTATCTCCAAAGC CATATATGAC GGCGGTAGTAGAGGATTTGTGTACTTGTTTCGATAATGCCCGATAAATTCTTCTACTTTT TTAGATTGGC AATATTGAGTAATCGAATCGATTAATTCTTGATGCTTCCCAGTGTCATAAAATAAACTTT TATTCAGATA CCAATGAGGATCATAATCATGGGAGTAGTGATAAATCATTTGAGTTCTGACTGCTACTTC TATCGACTCC GTAGCATTAAAAATAAGCATTCTCAAGGATTTATCAAACTTGTATAGATTTGGCCGGCCC GTCAAAAGGG CGACACCCCATAATTAGCCCGGGCGAAAGGCCCAGTCTTTCGACTGAGCCTTTCGTTTTA TTTGATGCCT GGCAGTTCCCTACTCTCGCATGGGGAGTCCCCACACTACCATCGGCGCTACGGCGTTTCA CTTCTGAGTT CGGCATGGGGTCAGGTGGGACCACCGCGCTACTGCCGCCAGGCAAACAAGGGGTGTTATG AGCCATATTC AGGTATAAArGGGCTCGCGATAATGTTCAGAATTGGTTAATTGGTTGTAACACTGACCCC TATTTGTTTA TTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAACCCTGATAAATGCTT CAATAATATT GAAAAAGGAAGAATATGAGTATTCAACATTTCCGTGTCGCCCTTATTCCCTTTTTTGCGG CATTTTGCCT TCCTGTTTTTGCTCACCCAGAAACGCTGGTGAAAGTAAAAGATGCTGAAGATCAGTTGGG TGCACGAGTG GGTTACATCGAACTGGATCTCAACAGCGGTAAGATCCTTGAGAGTTTTCGCCCCGAAGAA CGTTTTCCAA TGATGAGCACTTTTAAAGTTCTGCTATGTGGCGCGGTATTATCCCGTATTGACGCCGGGC AAGAGCAACT CGGTCGCCGCATACACTATTCTCAGAATGACTTGGTTGAGTACTCACCAGTCACAGAAAA GCATCTTACG GATGGCATGACAGTAAGAGAATTATGCAGTGCTGCCATAACCATGAGTGATAACACTGCG GCCAACTTAC TTCTGACAACGATCGGAGGACCGAAGGAGCTAACCGCTTTTTTGCACAACATGGGGGATC ATGTAACTCG CCTTGATCGTTGGGAACCGGAGCTGAATGAAGCCATACCAAACGACGAGCGTGACACCAC GATGCCTGTA GCGATGGCAACAACGTTGCGCAAACTATTAACTGGCGAACTACTTACTCTAGCTTCCCGG CAACAATTAA TAGACTGGATGGAGGCGGATAAAGTTGCAGGACCACTTCTGCGCTCGGCCCTTCCGGCTG GCTGGTTTAT TGCTGATAAATCCGGAGCCGGTGAGCGTGGTTCTCGCGGTATCATCGCAGCGCTGGGGCC AGATGGTAAG CCCTCCCGTATCGTAGTTATCTACACGACGGGGAGTCAGGCAACTATGGATGAACGAAAT AGACAGATCG CTGAGATAGGTGCCTCACTGATTAAGCATTGGT

plasittid TAGAAAAACTCATCGAGCATCAAATGAAACTGCAATTTATTCATATCAGGATTATCAATA CCATATTTTT pAQ4 : : P ( cpcB) GAAAAAGCCGTTTCTGTAATGAAGGAGAAAACTCACCGAGGCAGTTCCATAGGATGGCAA GATCCTGGTA

TCGGTCTGCGATTCCGACTCGTCCAACATCAATACAACCTATTAATTTCCCCTCGTCAAA AATAAGGTTA

rCAAGTGAGAAATCACCATGAGTGACGACTGAATCCGGTGAGAATGGCAAAAGTTTATGC ATTTCTTTCC

Nhisfcag. a.dtsi{N AGACTTGTTCAACAGGCCAGCCATTACGCTCGTCATCAAAATCACTCGCATCAACCAAAC CGTTATTCAT p ) -ErraC . TCGTGATTGCGCCTGAGCGAGGCGAAATACGCGATCGCTGTTAAAAGGACAATTACAAAC AGGAATCGAG

TGCAACCGGCGCAGGAACACTGCCAGCGCATCAACAATATTTTCACCTGAATCAGGATAT TCTTCTAATA CCTGGAACGCTGTTTTTCCGGGGATCGCAGTGGTGAGTAACCATGCATCATCAGGAGTAC GGATAAAATG CTTGATGGTCGGAAGTGGCATAAATTCCGTCAGCCAGTTTAGTCTGACCATCTCATCTGT AACATCATTG GCAaCGCTACCTTTGCCATGTTTCAGAAACAACTCTGGCGCATCGGGCTTCCCATACAAG CGATAGATTG TCGCACCTGATTGCCCGACATTATCGCGAGCCCATTTATACCCATATAAATCAGCATCCA TGTTGGAATT TAaTCGCGGCCTCGACGTTTCCCGTTGAATATGGCTCATATTCTTCCTTTTTCAATATTA TTGAAGCATT TATCAGGGTTATTGTCTCATGAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAA ATAGGGGTCA GTGTTACAACCAATTAACCAATTCTGAACATTATCGCGAGCCCATTTATACCTGAATATG GCTCATAACA CCCCTTGTTTGCCTGGCGGCAGTAGCGCGGTGGTCCCACCTGACCCCATGCCGAACTCAG AAGTGAAACG CCGTAGCGCCGATGGT&GTGTGGGGACTCCCCATGCGAGAGT&GGG&A CTGCCAGGCATC&AAT&A&ACG AAAGGCTCAGTCGAAAGACTGGGCCTTTCGCCCGGGCTAATTAGGGGGTGTCGCCCTTTA CACGTACTTA GTCGCTGAAGGCCTCACTGGCCCCTGCAGGGATGGTGGAATGCTGGTTATCTGGTGGGGA TTAAGTGGTG TTTTACTAAAGCTTGAACAACTCAAGAAAGATTATATTCGCAATAACTGCCAATAATCCC AGCATCTTGA GAAAATCCAGCAAACCGGGGGCAAAACACCAGCAAGAAGCCAGCAGACTATCACCAAATC CCCAGCGTAC AGCTAGAAATAACTGAGCAGTTGTATTCAATTACCTTCTGGTCAAGCCGAGGAAATTTCC CCACACCTTA TACACCTCTGGAAGGTTTTTTTGACGAAGCGCAAAATATCCACAATCGGCTGGGGACTTC TTCTGTCAGA AAATGGCAGAAATTTTTGAATGTGTTGGCGATCGCCCTCATCAATGATTATTAGAGAACT TTTGTCCCTG ATGTTGGGAATACTCTTGATGACAATTGTGATTGCTCAAAGAAGAAAGAAATTTGGAGTA AATCTCTAAA AGGGGACTGAAATATTTGTATGGTCAGCATGACCACTGAAATGGAGAGAAGTCTAAGACA GTAGATGTCT TAGATATAAGCCTCATTAGAAGCCATGCCATAAAACAGATTTTGTGGATGAAACAACTTG AAATAGTTCA GTTGTAGACCATGTTATAAACATTTATTCTTAACACAGTGACACATTAATGACTCATATA TCCGTCCAAA AAAAACTAAAATGTTTGTAAATTTAGTTTTGCGGCCGCGTCGACTTCGTTATAAAATAAA CTTAACAAAT CTATACCCACCTGTAGAGAAGAGTCCCTGAATATCAAAATGGTGGGATAAAAAGCTCAAA AAGGAAAGTA GGCTGTGGTTCCCTAGGCAACAGTCTTCCCTACCCCACTGGAAACTAAAAAAACGAGAAA AGTTCGCACC GAACATCAATTGCATAATTTTAGCCCTAAAACATAAGCTGAACGAAACTGGTTGTCTTCC CTTCCCAATC CAGGACAATCTGAGAATCCCCTGCAACATTACTTAACAAAAAAGCAGGAATAAAATTAAC AAGATGTAAC AGACATAAGTCCCATCACCGTTGTATAAAGTTAACTGTGGGATTGCAAAAGCATTCAAGC CTAGGCGCTG AGCTGTTTGAGCATCCCGGTGGCCCTTGTCGCTGCCTCCGTGTTTCTCCCTGGATTTATT TAGGTAATAT CTCTCATAA&TCCCCGGGTAGTTAACGAAAGTTAATGGAGATCAGTAACAATAACT CTAGGGTCATTACT TTGGACTCCCTCAGTTTATCCGGGGGAATTGTGTTTAAGAAAATCCCAACTCATAAAGTC AAGTAGGAGA TTAATCATATGCACCATCACCACCATCATGGAGGCGGACAGCAACTGACCGATCAAAGCA AAGAACTGGA CTTCAaGAGCGAGACGTACAAAGACGCCTATAGCCGCATTAACGCGATCGTCATTGAAGG CGAACAAGAG GCGCATGAAAACTACATCACCCTGGCGCAGCTGCTGCCTGAGAGCCACGACGAACTGATT CGCCTGAGCA AA&TGGAGAGCCGTCACAAGAAAGGTTTTGAGGCGTGTGGCCGCAATCTGGCGGTG ACCCCGGACCTGCA ATTTGCGAAGGAGTTCTTTAGCGGTCTGCACCAGAATTTCCAGACGGCCGCAGCCGAGGG CAAAGTCGTC ACTTGTTTGTTGATCCAGAGCCTGATTATTGAATGCTTTGCTATTGCGGCGTACAACATT TACATTCCGG TCGCCGATGACTTTGCGCGTAAAATCACGGAAGGTGTTGTCAAAGAGGAGTATTCCCACC TGAATTTCGG TGAAGTGTGGTTGAAGGAACATTTTGCGGAATCTAAAGCCGAATTGGAACTGGCAAATCG CCAGAACCTG CCGATCGTTTGGAAGATGCTGAACCAAGTGGAAGGTGATGCACATACGATGGCGATGGAG AAGGACGCAT TGGTTGAGGACTTTATGATTCAGTATGGCGAAGCACTGTCCAATATCGGTTTCAGCACCC GTGATATCAT GCGTCTGAGCGCCTATGGCCTGATCGGTGCCTAAGAGCTCCTCGAGGAATTCGGTTTTCC GTCCTGTCTT GATTTTCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGCATTTGTTTTTGTTTATTGC AAAAACAAAA AATATTGTTACAAATTTTTACAGGCTATTAAGCCTACCGTCATAAATAATTTGCCATTTA CTAGTTTTAA TTAACGTGCTATAATTATACTAATTTTATAAGGAGGAAAAAATATGGGCATTTTTAGTAT TTTTGTAATC AGCACAGTTCATTATCAACCAAACAAAAAATAAGTGGTTATAATGAATCGTTAATAAGCA AAATTCATAT

AaCCAaATTAAAGAGGGTTATAATGAACGAGAAAAATATAAAACACAGTCAAAACTT TATTACTTCAAAA CATAATATAGATAAAATAATGACAAATATAAGATTAAATGAACATGATAATATCTTTGAA ATCGGCTCAG GAaAaGGCCATTTTACCCTTGAATTAGTAAAGAGGTGTAATTTCGTAACTGCCATTGAAA TAGACCATAA ArTATGCAAAACTACAGAAAATAAACTTGTTGATCACGATAATTTCCAAGTTTTAAACAA GGATATATTG CAGTTTAAATTTCCTAAAAACCAATCCTATAAAATATATGGTAATATACCTTATAACATA AGTACGGATA TAATACGCAAAATTGTTTTTGATAGTATAGCTAATGAGATTTATTTAATCGTGGAATACG GGTTTGCTAA AAGATTATTAAATACAAAACGCTCATTGGCATTACTTTTAATGGCAGAAGTTGATATTTC TATATTAAGT ATGGTTCCAaGAGAATATTTTCATCCTAAACCTAAAGTGAATAGCTCACTTATCAGATTA AGTAGAAAAA AATCAAGAATATCACACAAAGATAAACAAAAGTATAATTATTTCGTTATGAAATGGGTTA ACAAAGAATA CAaGAAaATATTTACAAAAAATCAATTTAACAATTCCTTAAAACATGCAGGAATTGACGA TTTAAACAAT ArTAGCTTTGAACAATTCTTATCTCTTTTCAATAGCTATAAATTATTTAATAAGTAAGTT AAGGGATGCA TAAACTGCATCCCTTAACTTGTTTTTCGTGTGCCTATTTTTTGTGGCGCGCCCAGTTTCC TTTACTGGCC CTAAAGTCGCTGTGGCTAGGGTTCCGAAGGGGCATTATTGGCTCGCGGCTTTACAACCTT GATAAGGAGA GAGATGACAGTTTTTTTTCTCTTTTGCTTAGTAAAACAGCAAATTTAAGGCATGTTAAAG AGCAGTAGAA CGAAATGGTTGAGCCGGCCTCGATACACTCAATTAACTACTAATAGCTTCAATAAATTTT GGGACGATTG AAGCrATTTTTTTGAAAATCAACTCTTAATATCTCCTGTCTCAAAAGAGTTAATTGCTAA ACAAAAGCCA GTTTCAGCGAAAAATCTAGAGTTTTATAGGTTCGTTCTCAGTACAGGACAAAAAGTTTGA AAAGGATAGA GGGAGAGGGTTTGATGGAAATAAGCACAAATCAATCAAGCCCTCATGAATCAGATTAGCG AAATTCGCCG CCAaTTGCGACCTCATCTCGGATGGCATGGAGCCAGACTGTCATTTATCGCCCTCTTCCT GGTGGCACTG TTCCGAGCAAAAACCGTCAATCTCGCCAAACTCGCCACCGTCTGGGGAGGCAATGCAGCA GAAGAGTCTA ATTACAAACGCATGCAGCGATTCTTTCAGTCCTTTGACGTCAACATGGACAAAATCGCCA GGATGGTAAT GAATATCGCGGCTATCCCGCAACCTTGGGTCTTAAGCATCGACCGCACCAACGGCCGGCC TACATGGCCC GTCAATCGAAGGGCGACACAAAATTTATTCTAAATGCATAATAAATACTGATAACATCTT ATAGTTTGTA TTATATTTTGTATTATCGTTGACATGTATAATTTTGATATCAAAAACTGATTTTCCCTTT ATTATTTTCG AGATTTATTTTCTTAATTCTCTTTAACAAACTAGAAATATTGTATATACAAAAAATCATA AATAATAGAT GAATAGTTTAATTATAGGTGTTCATCAATCGAAAAAGCAACGTATCTTATTTAAAGTGCG TTGCTTTTTT CTCATTTATAAGGTTAAATAATTCTCATATATCAAGCAAAGTGACAGGCGCCCTTAAATA TTCTGACAAA

GATTACTCGTTATCAGAACCGCCCAGGGGGCCCGAGCTTAAGACTGGCCGTCGTTTT ACAACACAGAAAG AGTTTGTAGAAACGCAAAAAGGCCATCCGTCAGGGGCCTTCTGCTTAGTTTGATGCCTGG CAGTTCCCTA CTCTCGCCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGCGA GCGGTATCAG

CrCACrCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGA ACATGTGAGCAAA AGGCCAGCAaAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGGCT CCGCCCCCCT GACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTATAA AGATACCAGG CGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGGAT ACCTGTCCGC CTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGTTC GGTGTAGGTC GTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCTTA TCCGGTAACT ATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGGTA ACAGGATTAG CAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGGCTAACTACGGCTA CACTAGAAGA ACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTAGC TCTTGATCCG GCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCGCA GAAAAAAAGG ATCTCAAGftAGATCCTTTGATCTTTTCT&CGGGGTCTG&CGCTC&GT GGA¾CGACGCGCGCGTA¾CTC&C GTTJ^GGATTTTGGTCATGAGCTTGCGCCGTCCCGTCAAGTCAGCGTAATGCTCTGCTTT

ACCAATGCTTAATCAGTGAGGCACCTATCTCAGCGATCTGTCTATTTCGTTCATCCATAG TTGCCTGACT

pAQ7: :P(nir07 CCCCGTCGTGTAGAT^CTACGATACGGGAGGGCTTACCATCTGGCCCCAGCGCTGCGATG ATACCGCGA

GAACCACGC CACCGGCTCCGGATTTATCAGCAATAAACCAGCCAGCCGGAAGGGCCGAGCGCAGAAGTG

) -carB-@nbD~ GTCCTGCJ-ACTTTATCCGCCTCCATCCAGTCTATTAATTGTTGCCGGGAAGCTAGAGTA AGTAGTTCGCC

AGTTAATAGTTTGCGCAACGTTGTTGCCATCGCTACAGGCATCGTGGTGTCACGCTCGTC GTTTGGTATG GCTTCATTCAGCTCCGGTTCCCAACGATCAAGGCGAGTTACATGATCCCCCATGTTGTGC AAAAAAGCGG TTAGCTCCTTCGGTCCTCCGATCGTTGTCAGAAGTAAGTTGGCCGCAGTGTTATCACTCA TGGTTATGGC

CGCCACATAGCAGAACTTTAAAAGTGCTCATCATTGGAAAACGTTCTTCGGGGCGAA AACTCTCAAGGAT CTTACCGCTGTTGAGATCCAGTTCGATGTAACCCACTCGTGCACCCAACTGATCTTCAGC ATCTTTTACT TTCACCAGCGTTTCTGGGTGAGCAAAAACAGGAAGGCAAAATGCCGCAAAAAAGGGAATA AGGGCGACAC

GAGCGGATACATATTTGAATGTATTTAGAAAAATAAACAAATAGGGGTCAGTGTTAC AACCAATTAACCA ATTCTGAACATTATCGCGAGCCCATTTATACCTGAATATGGCTCATAACACCCCTTGTTT GCCTGGCGGC AGTAGCGCGGTGGTCCCACCTGACCCCATGCCGAACTCAGAAGTGAAACGCCGTAGCGCC GATGGTAGTG

GGGCCTTTCGCCCGGGCTAATTATGGGGTGTCGCCCTTATTCGACTCTATAGTGAAG TTCCTATTCTCTA

GAAAGTATAGGAACTTCTGAAGTGGGGCCTGCAGGGCCACCACAGCCAAATTCATCG TTAATGTGGACTT

GGTTAAAACAGCCCGCAGGTGACGATCAATGCCTTTGACCTTCACATCCGACGGAAT ACAAACCAAGCCA CAGAGTTCACAGCGCCAGTCTGCATCCTCTTTTACTTGTAAGGCGATCGCCTGCCAATCA TCAGAATATC

GGCCAACATCACAGCCAATACTGCGGCCGCTACTCATTAGTTAAGTGTAATGCAGAA AACGCATATTCTC TATTAAACTTACGCATTAATACGAGAATTTTGTAGCTACTTATACTATTTTACCTGAGAT CCCGACATAA CCTTAGAAGTATCGAAATCGTTACATAAACATTCACACAAACCACTTGACAAATTTAGCC AATGTAAAAG

AGTAGCATAAATCAA CAAAA ACCCTGCGGGAAGGCTGCGCCAACAAA^

CTATTAGAGCATCGATTCATTAATCAAAAACCTTACCCCCCAGCCCCCTTCCCTTGT AGGGAAGTGGGAG

CJ-GCGATGTTCACGACGCCACAGACGGCGTCACCGAAACCGCACTCGACGACGAGC AGTCGACCCGCCGC ATCGCCGAGCTGTACGCCACCGATCCCGAGTTCGCCGCCGCCGCACCGTTGCCCGCCGTG GTCGACGCGG CGCACAAACCCGGGCTGCGGCTGGCAGAGATCCTGCAGACCCTGTTCACCGGCTACGGTG ACCGCCCGGC GCTGGGATACCGCGCCCGTGAACTGGCCACCGACGAGGGCGGGCGCACCGTGACGCGTCT GCTGCCGCGG TTCGACACCCTCACCTACGCCCAGGTGTGGTCGCGCGTGCAAGCGGTCGCCGCGGCCCTG CGCCACAACT TCGCGCAGCCGATCTACCCCGGCGACGCCGTCGCGACGATCGGTTTCGCGAGTCCCGATT ACCTGACGCT GGATCTCGTATGCGCCTACCTGGGCCTCGTGAGTGTTCCGCTGCAGCaa^CGCACCGGTC AGCCGGCTC GCCCCGATCCTGGCCGAGGTCGAACCGCGGATCCTCACCGTGAGCGCCGAATACCTCGAC CTCGCAGTCG AATCCGTGCGGGACGTCAACTCGGTGTCGCAGCTCGTGGTGTTCGACCATCACCCCGAGG TCGACGACCA CCGCGACGCACTGGCCCGCGCGCGTGAACAACTCGCCGGCAAGGGCATCGCCGTCACCAC CCTGGACGCG ATCGCCGACGAGGGCGCCGGGCTGCCGGCCGAACCGATCTACACCGCCGACCATGATCAG CGCCTCGCGA TGATCCTGTACACCTCGGGTTCCACCGGCGCACCCAAGGGTGCGATGTACACCGAGGCGA TGGTGGCGCG GCTGTGGACCATGTCGTTCATCACGGGTGACCCCACGCCGGTCATCAACGTCAACTTCAT GCCGCTC-ftAC CACCTGGGCGGGCGCATCCCCATTTCCACCGCCGTGCAGAACGGTGGAACCAGTTACTTC GTACCGGAAT CCGACATGTCCACGCTGTTCGAGGATCTCGCGCTGGTGCGCCCGACCGAACTCGGCCTGG TTCCGCGCGT CGCCGACATGCTCTACCAGCACCACCTCGCCACCGTCGACCGCCTGGTCACGCAGGGCGC CGACGAACTG ACCGCCGAGAAGCAGGCCGGTGCCGAACTGCGTGAGCAGGTGCTCGGCGGACGCGTGATC ACCGGATTCG

CGGCTACGGGCTCACCGAGACCGGCGCCGTGACACGCGACGGTGTGATCGTGCGGCC ACCGGTGATCGAC TACAAGCTGATCGACGTTCCCGAACTCGGCTACTTCAGCACCGACAAGCCCTACCCGCGT GGCGAACTGC

GGACGGCTACTACCACACCGGCGACGTCATGGCCGAGACCGCACCCGACCACCTGGT GTACGTGGACCGT CGCAACAACGTCCTCAAACTCGCGCAGGGCGAGTTCGTGGCGGTCGCCAACCTGGAGGCG GTGTTCTCCG GCGCGGCGCTGGTGCGCCAGATCTTCGTGTACGGCAACAGCGAGCGCAGTTTCCTTCTGG CCGTGGTGGT CCCGACGCCGGAGGCGCTCGAGCAGTACGATCCGGCCGCGCTCAAGGCCGCGCTGGCCGA CTCGCTGCAG CGCACCGCaCGCGACGCCGAACTGCAATCCTACGAGGTGCCGGCCGATTTCATCGTCGAG ACCGAGCCGT

GCGGCCGCCLACACAACCGGTGATCGACACCCTCACCCAGGCCGCTGCCACGATCCT CGGCACCGGGAGCG AGGTGGCATCCGACGCCCACTTCACCGACCTGGGCGGGGATTCCCTGTCGGCGCTGACAC TTTCGAACCT GCTGAGCGATTTCTTCGGTTTCGAAGTTCCCGTCGGCACCATCGTGAACCCGGCCACCAA CCTCGCCCAA CTCGCCCAGCACATCGAGGCGCAGCGCACCGCGGGTGACCGCAGGCCGAGTTTCACCACC GTGCACGGCG CGGACGCCaCCGAGATCCGGGCGAGTGAGCTGACCCTGGACAAGTTCATCGACGCCGAAA CGCTCCGGGC

GGCCGGTTCCTCACGTTGCAGTGGCTGGAACGCCTGGCACCTGTCGGCGGCACCCTC ATCACGATCGTGC GGGGCCGCGACGACGCCGCGGCCCGCGCACGGCTGACCCAGGCCTACGACACCGATCCCG AGTTGTCCCG CCGCTTCGCCGAGCTGGCCGACCGCCACCTGCGGGTGGTCGCCGGTGACATCGGCGACCC GAATCTGGGC

ACCACGTGCTCCCCTACCGGCAGCTGTTCGGCCCCAACGTCGTGGGCACGGCCGAGG TGATCAAGCTGGC CCTCACCGftACGGATCA¾GCCCGTCACGTACCTGTCCACCGTGTCGGTGGCC&T GGGG&TCCCCGACTTC GAGGAGGACGGCG&C&TCCGG&CCGTG&GCCCGGTGCGCCCGCT CGACGGCGG&T&CGCCAACGGCT&CG GCAACAGCAAGTGGGCCGGCG&GGTGCTGCTGCGGGAGGCCCACG&TCTGTG CGGGCTGCCCGTGGCGAC GTTCCGCTCGGACATG&TCCTGGCGC&TCCGCGCTACCGCGGTC&GGT CA&CGTGCCAGACATGTTCACG CGACTCCTGTTG&GCCTCTTGATC&CCGGCGTCGCGCCGCGGTCGTTCTACA TCGG&G&CGGTG&GCGCC CGCGGGCGCACTACCCCGGCCTGACGGTCGATTTCGTGGCCGAGGCGGTCACGACGCTCG GCGCGCAGCA GCGCGAGGGATACGTGTCCTACGACGTGATGAACCCGCACGACGACGGGATCTCCCTGGA TGTGTTCGTG GACTGGCTGATCCGGGCGGGCCATCCGATCGACCGGGTCGACGACTACGACGACTGGGTG CGTCGGTTCG AGACCGCGTTGACCGCGCTTCCCGAGAAGCGCCGCGCACAGACCGTACTGCCGCTGCTGC ACGCGTTCCG CGCTCCGCAGGCACCGTTGCGCGGCGCACCCGAACCCACGGAGGTGTTCCACGCCGCGGT GCGCACCGCG AAGGTGGGCCCGGGAGACATCCCGCACCTCGACGAGGCGCTGATCGACAAGTACATACGC GATCTGCGTG AGTTCGGTCTGATCTCGAGCTCGTGAGGTACCCACAAGGAGGTTTTTACAATGAAAACGA CCCACACCAG CTTACCATTTGCCGGCCACACGTTACATTTCGTCGAATTTGATCCGGCGAACTTTTGTGA ACAAGACCTG TTGTGGCTGCCGCATTATGCCCAGCTGCAGCACGCAGGCCGTAAGCGTAAAACTGAACAT CTGGCCGGTC GCATTGCGGCAGTGTATGCCCTGCGCGAGTACGGCTACAAATGCGTGCCGGCCATTGGTG AACTGCGTCA ACCGGTTTGGCCGGCAGAAGTTTACGGTTCCATCTCCCACTGCGGTACTACCGCGTTGGC GGTTGTGTCT CGCCAGCCGATCGGTATTGATATTGAAGAGATATTCTCTGTCCAGACGGCACGCGAGCTG ACGGACAACA TCATTACCCCGGCAGAGCACGAGCGTCTGGCGGACTGTGGTCTGGCGTTCAGCCTGGCGC TGACCCTGGC ATTCAGCGCAAAAGAGAGCGCGTTCAAGGCTTCCGAGATCCAAACCGATGCGGGCTTCCT GGATTATCAA ATCATCAGCTGGAACAAGCAACAGGTTATCATTCACCGTGAGAATGAGATGTTTGCCGTC CATTGGCAGA TTAAaGAGAAAATCGTTATCACCCTGTGCCAGCACGACTGAGAATTCGGTTTTCCGTCCT GTCTTGATTT TCAAGCAAACAATGCCTCCGATTTCTAATCGGAGGCATTTGTTTTTGTTTATTGCAAAAA CAAAAAATAT TGTTACAaATTTTTACAGGCTATTAAGCCTACCGTCATAAATAATTTGCCATTTACTAGT TTTTAATTAA ACCCCTATTTGTTTATTTTTCTAAATACATTCAAATATGTATCCGCTCATGAGACAATAA CCCTGATAAA TGCTTCAATAATATTGAAAAAGGAAGAGTATGATTGAACAAGATGGCCTGCATGCTGGTT CTCCGGCTGC TTGGGTGGAACGCCTGTTTGGTTACGACTGGGCTCAGCTGACTATTGGCTGTAGCGATGC AGCGGTTTTC CGTCTGTCTGCACAGGGTCGTCCGGTTCTGTTTGTGAAAACCGACCTGTCCGGCGCACTG AACGAACTGC AGGACGAAGCGGCCCGTCTGTCCTGGCTCGCGACGACTGGTGTTCCGTGCGCGGCAGTTC TGGACGTAGT TACTGAAGCCGGTCGCGATTGGCTGCTGCTGGGTGAAGTTCCGGGTCAGGATCTGCTGAG CAGCCACCTC GCTCCGGCAGAAAAAGTTTCCATCATGGCGGACGCGATGCGCCGTCTGCACACCCTGGAC CCGGCAACTT GCCCGTTTGACCATCAGGCTAAACACCGTATTGAACGTGCACGCACTCGTATGGAAGCGG GTCTGGTTGA TCAGGACGACCTGGATGAAGAGCACCAGGGCCTCGCACCGGCGGAACTGTTTGCACGTCT GAAAGCCCGC ATGCCGGACGGCGAAGACCTGGTGGTAACGCATGGCGACGCTTGTCTGCCAAACATTATG GTGGAAAACG GCCGCTTCTCTGGTTTTATTGACTGTGGCCGTCTGGGTGTAGCTGATCGCTATCAGGATA TCGCCCTCGC TACCCGCGATATTGCAGAAGAACTGGGTGGTGAATGGGCTGACCGTTTCCTGGTGCTGTA CGGTATCGCA GCGCCGGATTCTCAGCGCATTGCCTTCTACCGTCTGCTGGATGAGTTCTTCTAAGGCGCG CCGAAACTGC GCCAAGAaTAGCTCACTTCAAATCAGTCACGGTTTTGTTTAGGGCTTGTCTGGCGATTTT GGTGACATAG ACAGrCACAGCAACAGTAGCCACAAAACCAAGAATCCGGATCGACCACTGGGCAATGGGG TTGGCGCTGG TGCTTTCTGTGCCGAGGGTCGCAAGATTTCCGGCCAGGGAGCCAATGTAGACATACATGA TGGTGCCAGG GATCATCCCCACAGAGCCGAGGACATAGTCTTTTAGGGAAACGCCCGTGACCCCATAGGC ATAGTTAAGC AGATTAAAGGGAAATACAGGTGAGAGACGCGTCAGGAGAACAATCTTCAGGCCTTCCTTG CCCACAGCTT CGTCGATGGCGCGAAATTTCGGGTTGTCGGCGATTTTTTGGCTCACCCATTGGCGGGCCA GATAACGACC CACTAGGAAAGCAGCGATCGCTCCTAGGGTTGCGCCAACAAAGACGTAAATTGATCCTAA AGCGACACCA

AaAaCAACCCCGGCTCCCAAGGTCAGAATCGACCCCGGTAGAAAAGCCACCGTCGCC ACCACATAAAGCA CCATAAAGGCGATGGCCGGCCAAAATGAAGTGAAGTTCCTATACTTTCTAGAGAATAGGA ACTTCTATAG TGAGTCGAaTAAGGGCGACACAAAATTTATTCTAAATGCATAATAAATACTGATAACATC TTATAGTTTG TATTATATTTTGTATTATCGTTGACATGTATAATTTTGATATCAAAAACTGATTTTCCCT TTATTATTTT CGAGATTTATTTTCTTAATTCTCTTTAACAAACTAGAAATATTGTATATACAAAAAATCA TAAATAATAG ATGAATAGTTTAATTATAGGTGTTCATCAATCGAAAAAGCAACGTATCTTATTTAAAGTG CGTTGCTTTT TTCTCATTTATAAGGTTAAATAATTCTCATATATCAAGCAAAGTGACAGGCGCCCTTAAA TATTCTGACA AATGCTCTTTCCCTAAACTCCCCCCATAAAAAAACCCGCCGAAGCGGGTTTTTACGTTAT TTGCGGATTA ACGATTACTCGTTATCAGAACCGCCCAGGGGGCCCGAGCTTAAGACTGGCCGTCGTTTTA CAACACAGAA AGAGTTTGTAGAAACGCAAAAAGGCCATCCGTCAGGGGCCTTCTGCTTAGTTTGATGCCT GGCAGTTCCC TACTCrCGCCTTCCGCTTCCTCGCTCACTGACTCGCTGCGCTCGGTCGTTCGGCTGCGGC GAGCGGTATC AGCTCACTCAAAGGCGGTAATACGGTTATCCACAGAATCAGGGGATAACGCAGGAAAGAA CATGTGAGCA AAAGGCCAGCAAAAGGCCAGGAACCGTAAAAAGGCCGCGTTGCTGGCGTTTTTCCATAGG CTCCGCCCCC CTGACGAGCATCACAAAAATCGACGCTCAAGTCAGAGGTGGCGAAACCCGACAGGACTAT AAAGATACCA GGCGTTTCCCCCTGGAAGCTCCCTCGTGCGCTCTCCTGTTCCGACCCTGCCGCTTACCGG ATACCTGTCC GCCTTTCTCCCTTCGGGAAGCGTGGCGCTTTCTCATAGCTCACGCTGTAGGTATCTCAGT TCGGTGTAGG TCGTTCGCTCCAAGCTGGGCTGTGTGCACGAACCCCCCGTTCAGCCCGACCGCTGCGCCT TATCCGGTAA CTATCGTCTTGAGTCCAACCCGGTAAGACACGACTTATCGCCACTGGCAGCAGCCACTGG TAACAGGATT AGCAGAGCGAGGTATGTAGGCGGTGCTACAGAGTTCTTGAAGTGGTGGGCTAACTACGGC TACACTAGAA GAACAGTATTTGGTATCTGCGCTCTGCTGAAGCCAGTTACCTTCGGAAAAAGAGTTGGTA GCTCTTGATC CGGCAAACAAACCACCGCTGGTAGCGGTGGTTTTTTTGTTTGCAAGCAGCAGATTACGCG CAGAAAAAAA GGATCTCAAGAAGATCCTTTGATCTTTTCTACGGGGTCTGACGCTCAGTGGAACGACGCG CGCGTAACTC ACGTTAAGGGATTTTGGTCATGAGCTTGCGCCGTCCCGTCAAGTCAGCGTAATGCTCTGC TTTT Long-chain fatty ATP + a long- long-chain fatty 6.2.1. fadD Escherichia coli NP_416319 acid CoA-ligase chain fatty acid acid CoA-ligase 3 fadD Synechococcus YP 001733 activity + CoA = AMP elongatus 936

+ diphosphate TTCOO Thermus YP 004054 + an acyl-CoA

79 thermophilus

HB27