Title:
SYSTEM FOR THE ASSEMBLY AND MODIFICATION OF NON-RIBOSOMAL PEPTIDE SYNTHASES
Document Type and Number:
WIPO Patent Application WO/2019/138117
Kind Code:
A1
Abstract:
The present invention pertains to a system for the assembly and modification of non- ribosomal peptide synthases (NRPS). The system uses novel well defined building blocks (units) comprising condensation subdomains. This strategy allows for the efficient combination of assembly units referred to as eXchange Units (XU2.0) independent on their natural occurring specificity for the subsequent NRPS adenylation domain. The system of the invention allows for the easy assembly of NRPS having any amino acid sequence of choice, without any restrictions due to natural occurring NRPS units. The system also allows the exchange of natural NRPS building blocks with the inventive XU2.0 leading to the production of modified peptides. The invention provides the system, their individual exchange units, nucleic acids encoding these units, as well as methods and uses thereof.
Inventors:
BOZHÜYÜK KENAN (DE)
LINCK ANNABELL (DE)
BODE HELGE (DE)
LINCK ANNABELL (DE)
BODE HELGE (DE)
Application Number:
PCT/EP2019/050853
Publication Date:
July 18, 2019
Filing Date:
January 15, 2019
Export Citation:
Assignee:
JOHANN WOLFGANG GOETHE UNIV FRANKFURT AM MAIN (DE)
International Classes:
C40B40/00; C12N9/00; C12P21/00
Domestic Patent References:
| WO2000052152A1 | 2000-09-08 | |||
| WO2001030985A1 | 2001-05-03 | |||
| WO2007014076A2 | 2007-02-01 | |||
| WO2017020983A1 | 2017-02-09 |
Foreign References:
| EP15002340A | 2015-08-05 |
Other References:
KENAN A. J. BOZHÜYÜK ET AL: "De novo design and engineering of non-ribosomal peptide synthetases", NATURE CHEMISTRY, vol. 10, no. 3, 11 December 2017 (2017-12-11), London, pages 275 - 281, XP055487878, ISSN: 1755-4330, DOI: 10.1038/nchem.2890
BINURAJ R. K. MENON ET AL: "Biosynthesis: Reprogramming assembly lines", NATURE CHEMISTRY, vol. 10, no. 3, 20 February 2018 (2018-02-20), London, pages 245 - 247, XP055488060, ISSN: 1755-4330, DOI: 10.1038/nchem.2941
RODERICH D. SÜSSMUTH ET AL: "Nonribosomal Peptide Synthesis-Principles and Prospects", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 56, no. 14, 27 March 2017 (2017-03-27), pages 3770 - 3821, XP055487875, ISSN: 1433-7851, DOI: 10.1002/anie.201609079
KENAN A J BOZHUEYUEK ET AL: "Modification and de novo design of non-ribosomal peptide synthetases (NRPS) using specific assembly points within condensation domains", BIORXIV, 24 June 2018 (2018-06-24) - 24 June 2018 (2018-06-24), XP055487945, Retrieved from the Internet DOI: 10.1101/354670
"Sequence Analysis Software Package of the Genetics Computer Group", UNIVERSITY OF WISCONSIN BIOTECHNOLOGY CENTER
"Genbank", Database accession no. PRJNA224116
"Genbank", Database accession no. PRJNA328553
"Genbank", Database accession no. PRJNA328572
ALTSCHUL SF; GISH W; MILLER W; MYERS EW; LIPMAN DJ, J. MOL. BIOL., vol. 0, no. 21, pages 403 - 410
BELSHAW PJ; WALSH CT; STACHELHAUS T, SCIENCE, vol. 284, 1999, pages 486 - 9,489
BLOUDOFF, K; RODIONOV, D; SCHMEING, TM., J. MOL. BIOL., vol. 425, 2013, pages 3137 - 3150
BODE HB; REIMER D; FUCHS SW; KIRCHNER F; DAUTH C, KEGLER C; LORENZEN W; BRACHMANN AO; GRÜN P, CHEMISTRY - A EUROPEAN JOURNAL, vol. 18, 2012, pages 2342
BODE HB; BRACHMANN AO; JADHAV KB; SEYFARTH L; DAUTH C; FUCHS SW; KAISER M; WATERFIELD NR; SACK H; HEINEMANN SH, ANGEW CHEM INT ED ENGL, vol. 54, 2015, pages 10352
BOZHUEYUEK KAJ; FLEISCHHACKER F; LINCK A; TIETZE A; NIESERT CP; BODE HB, NAT CHEM., 2017
BRUNER SD; WEBER T; KOHLI RM; SCHWARZER D; MARAHIEL MA; WALSH CT; STUBBS MT, STRUCTURE, vol. 10, 2002, pages 301 - 310
CAI X; NOWAK S; WESCHE F; BISCHOFF I; KAISER M; FÜRST R; BODE HB, NAT CHEM., vol. 9, 2017, pages 379 - 386
CALCOTT, MJ; ACKERLEY DF, BIOTECHNOL LETT, vol. 36, 2014, pages 2407 - 16
CANE DE; WALSH CT; KHOSLA C, SCIENCE, vol. 282, 1989, pages 63 - 68
CLUGSTON SL; SIEBER SA; MARAHIEL MA; WALSH CT, BIOCHEMISTRY, vol. 42, 2003, pages 12095 - 104
CONTI E; STACHELHAUS T; MARAHIEL MA; BRICK P, EMBO J., vol. 199, no. 16, pages 4174 - 83
COSMINA, P.; RODRIGUEZ, F.; FERRA, F.; GRANDI, G.; PEREGO, M.; VENEMA, G.; SINDEREN, D., MOL MICROBIOL, vol. 8, 1993, pages 821 - 831
DE CRÉCY-LAGARD V; MARLIERE P; SAURIN W, C R ACAD SCI III, vol. 318, 1995, pages 927 - 36
DU L; LOU L, NAT. PROD. REP., vol. 27, 2009, pages 255 - 78
EMMEL EA; VERWEIJ CL; DURAND DB; HIGGINS KM, SCIENCE, no. 246, 1989, pages 1617 - 1620
FUCHS SW; PROSCHAK A; JASKOLLA TW.; KARAS M; BODE HB, ORG BIOMOL CHEM, vol. 9, 2011, pages 3130 - 3132
FUCHS SW; SACHS CC; KEGLER C; NOLLMANN FI; KARAS M; BODE HB, ANALYTICAL CHEMISTRY, vol. 84, 2012, pages 6948
FUCHS SW; BOZHÜYÜK KA; KRESOVIC D; GRUNDMANN F; DILL V; BRACHMANN AO; WATERFIELD NR; BODE HB: "Angewandte Chemie", vol. 52, 2013, pages: 4108 - 4112
GAO, X.; HAYNES SW; AMES BD; WANG P; VIEN LP; WALSH CT; TANG Y, NAT. CHEM. BIOL., vol. 8, 2012, pages 823 - 830
GAUDELLI NM; TOWNSEND CA, NAT. CHEM. BIOL., vol. 10, 2014, pages 251 - 258
GIETZ RD; SCHIESTL RH, NAT PROTOC, vol. 2, 2007, pages 1 - 4
HARVEY AL; EDRADA-EBEL R; QUINN RJ, NAT REV DRUG DISCOV, vol. 14, 2015, pages 111 - 29
HAYNES SW; AMES BD; GAO X; TANG Y; WALSH CT, BIOCHEMISTRY, vol. 50, 2011, pages 5668 - 5679
HORSMAN ME; HARI TPA; BODDY CN, NAT. PROD. REP., 2015
ISHIZUKA M; TAKAYAMA H; TAKEUCHI T, J. ANTIBIOT., vol. 20, 1967, pages 15 - 24
KEATING TA; MARSHALL CG; WALSH CT; KEATING AE, NAT STRUCT BIOL., vol. 9, 2002, pages 522 - 6
KEGLER C; NOLLMANN FI; AHRENDT T; FLEISCHHACKER F; BODE E; BODE HB, CHEMBIOCHEM, vol. 15, 2014, pages 826
KOHLI RM; TRAUGER JW; SCHWARZER D; MARAHIEL MA; WALSH CT, BIOCHEMISTRY, vol. 40, 2001, pages 7099 - 7108
KOLB HC; SHARPLESS KB, DRUG DISCOV TODAY, vol. 8, 2003, pages 1128 - 37
KONZ, D.; KLENS, A.; SCHORGENDORFER, K.; MARAHIEL, M. A., CHEM BIOL, vol. 4, 1998, pages 927 - 937
KOPP F; MARAHIEL MA, NAT. PROD.RREP., vol. 24, 2007, pages 735 - 49
KORMAN TP; CRAWFORD JM; LABONTE JW; NEWMAN AG; WONG J; TOWNSEND CA; TSAI SC, PROC. NATL. ACAD. SCI. USA, vol. 107, 2010, pages 6246 - 6251
KRIES H; WACHTEL R; PABST A; WANNER B; NIQUILLE D; HILVERT D, ANGEW. CHEM. INT. ED., vol. 53, 2014, pages 10105 - 10108
KRONENWERTH M; BOZHÜYÜK KA; KAHNT AS; STEINHILBER D; GAUDRIAULT S; KAISER M; BODE HB, CHEMISTRY - A EUROPEAN JOURNAL, vol. 20, 2014, pages 17478 - 87
LEFEVRE F; ROBE P; JARRIN C; GINOLHAC A; ZAGO C; AURIOL D; VOGEL TM; SIMONET P; NALIN R, RES MICROBIOL, vol. 159, 2008, pages 153 - 61
LING LL; SCHNEIDER T; PEOPLES AJ; SPOERING AL, NATURE, vol. 517, 2015, pages 445 - 459
LOEFFLER W; TSCHEN J; VANITTANAKOM N, J. PHYTOPATHOL., vol. 115, 1986, pages 204 - 213
MARAHIEL MA, CHEM. BIOL., vol. 4, 1997, pages 561 - 567
MARAHIEL MA, NAT PROD REP, 2015
MEYER S; KEHR JC; MAINZ A; DEHM D; PETRAS D; SÜSSMUTH RD; DITTMANN E, CELL CHEM BIOL, vol. 23, 2016, pages 462 - 471
MITCHELL CA; SHI C; ALDRICH CC; GULICK AM, BIOCHEMISTRY, vol. 51, 2012, pages 3252 - 3263
NISHIHARA K; KANEMORI M; YANAGI H; YURA, T, APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 66, 2000, pages 884 - 889
NOLLMANN FI; DAUTH C; MULLEY G; KEGLER C; KAISER M; WATERFIELD NR; BODE HB, CHEMBIOCHEM, vol. 16, 2014, pages 205 - 8
LI R; OLIVER RA.; TOWNSEND CA, CELL CHEM BIOL, vol. 24, 2016, pages 24 - 34
PHELAN W; DU Y; MCLEAN JA; BACHMANN BO, CHEM BIOL., vol. 29, no. 16, 2009, pages 473 - 8
RAUSCH C; WEBER T; KOHLBACHER O; WOHLLEBEN W; HUSON DH, NUC. ACIDS. RES., vol. 33, 2005, pages 5799 - 5808
RAUSCH C; HOOF I; WEBER T; WOHLLEBEN W; HUSON DH, BMC EVOL BIOL., vol. 7, 2007, pages 78
REIMER D; COWLES KN; PROSCHAK A; NOLLMANN FI; DOWLING AJ; KAISER M; FFRENCH-CONSTANT R; GOODRICH-BLAIR H; BODE HB, CHEMBIOCHEM, vol. 14, 2013, pages 1991 - 1997
SAMEL SA; SCHOENAFINGER G; KNAPPE TA; MARAHIEL MA; ESSEN LO, STRUCTURE, vol. 15, 2007, pages 781 - 792
SCHIMMING O; FLEISCHHACKER F; NOLLMANN FI; BODE HB, CHEMBIOCHEM, vol. 15, 2014, pages 1290
SIEBER SA; MARAHIEL MA, CHEM. REV., vol. 105, 2005, pages 715 - 738
SLETTEN EM; BERTOZZI CR, ANGEW CHEM INT ED ENGL., vol. 48, 2009, pages 6974 - 98
SMITH S; TSAI S, NAT. PROD. REP., vol. 24, 2007, pages 1041 - 1072
STACHELHAUS T; SCHNEIDER A; MARAHIEL MA, SCIENCE, vol. 269, 1995, pages 69 - 72
STACHELHAUS T; MOOTZ HD; BERGENDAHL V; MARAHIEL MA, J BIOL CHEM., vol. 273, 1998, pages 22773 - 81
STACHELHAUS T; MOOTZ HD; MARAHIEL MA, CHEM. BIOL., vol. 6, 1999, pages 493 - 505
STRIEKER M; MARAHIEL MA, CURR. OPIN. STRUCT. BIOL., vol. 10, 2010, pages 234 - 240
SUNDLOV JA; GULICK AM, ACTA CRYSTALLOGR. D. BIOL. CRYSTALLOGR, vol. 6, 2013, pages 1482 - 1492
SÜSSMUTH RD; MAINZ A, ANGEW CHEM INT ED ENGL., vol. 56, 2017, pages 3770 - 3821
TAN XF; DAI YN; ZHOU K; JIANG YL; REN YM; CHEN Y; ZHOU CZ, ACTA CRYST, vol. D71, 2015, pages 873 - 881
TANOVIC A; SAMEL SA; ESSEN LO; MARAHIEL MA, SCIENCE, vol. 321, 2008, pages 659 - 663
TRAUGER JW; KOHLI RM; WALSH CT, NATURE, vol. 407, 2000, pages 215 - 218
TSENG CC; BRUNER SD; KOHLI RM; MARAHIEL MA; WALSH CT; SIEBER SA, BIOCHEMISTRY, vol. 41, 2002, pages 13350 - 13359
WINN, M; FYANS, JK; ZHUO Y; MICKLEFIELD J, NAT PROD REP, vol. 33, 2015, pages 317 - 347
BINURAJ R. K. MENON ET AL: "Biosynthesis: Reprogramming assembly lines", NATURE CHEMISTRY, vol. 10, no. 3, 20 February 2018 (2018-02-20), London, pages 245 - 247, XP055488060, ISSN: 1755-4330, DOI: 10.1038/nchem.2941
RODERICH D. SÜSSMUTH ET AL: "Nonribosomal Peptide Synthesis-Principles and Prospects", ANGEWANDTE CHEMIE INTERNATIONAL EDITION, vol. 56, no. 14, 27 March 2017 (2017-03-27), pages 3770 - 3821, XP055487875, ISSN: 1433-7851, DOI: 10.1002/anie.201609079
KENAN A J BOZHUEYUEK ET AL: "Modification and de novo design of non-ribosomal peptide synthetases (NRPS) using specific assembly points within condensation domains", BIORXIV, 24 June 2018 (2018-06-24) - 24 June 2018 (2018-06-24), XP055487945, Retrieved from the Internet
"Sequence Analysis Software Package of the Genetics Computer Group", UNIVERSITY OF WISCONSIN BIOTECHNOLOGY CENTER
"Genbank", Database accession no. PRJNA224116
"Genbank", Database accession no. PRJNA328553
"Genbank", Database accession no. PRJNA328572
ALTSCHUL SF; GISH W; MILLER W; MYERS EW; LIPMAN DJ, J. MOL. BIOL., vol. 0, no. 21, pages 403 - 410
BELSHAW PJ; WALSH CT; STACHELHAUS T, SCIENCE, vol. 284, 1999, pages 486 - 9,489
BLOUDOFF, K; RODIONOV, D; SCHMEING, TM., J. MOL. BIOL., vol. 425, 2013, pages 3137 - 3150
BODE HB; REIMER D; FUCHS SW; KIRCHNER F; DAUTH C, KEGLER C; LORENZEN W; BRACHMANN AO; GRÜN P, CHEMISTRY - A EUROPEAN JOURNAL, vol. 18, 2012, pages 2342
BODE HB; BRACHMANN AO; JADHAV KB; SEYFARTH L; DAUTH C; FUCHS SW; KAISER M; WATERFIELD NR; SACK H; HEINEMANN SH, ANGEW CHEM INT ED ENGL, vol. 54, 2015, pages 10352
BOZHUEYUEK KAJ; FLEISCHHACKER F; LINCK A; TIETZE A; NIESERT CP; BODE HB, NAT CHEM., 2017
BRUNER SD; WEBER T; KOHLI RM; SCHWARZER D; MARAHIEL MA; WALSH CT; STUBBS MT, STRUCTURE, vol. 10, 2002, pages 301 - 310
CAI X; NOWAK S; WESCHE F; BISCHOFF I; KAISER M; FÜRST R; BODE HB, NAT CHEM., vol. 9, 2017, pages 379 - 386
CALCOTT, MJ; ACKERLEY DF, BIOTECHNOL LETT, vol. 36, 2014, pages 2407 - 16
CANE DE; WALSH CT; KHOSLA C, SCIENCE, vol. 282, 1989, pages 63 - 68
CLUGSTON SL; SIEBER SA; MARAHIEL MA; WALSH CT, BIOCHEMISTRY, vol. 42, 2003, pages 12095 - 104
CONTI E; STACHELHAUS T; MARAHIEL MA; BRICK P, EMBO J., vol. 199, no. 16, pages 4174 - 83
COSMINA, P.; RODRIGUEZ, F.; FERRA, F.; GRANDI, G.; PEREGO, M.; VENEMA, G.; SINDEREN, D., MOL MICROBIOL, vol. 8, 1993, pages 821 - 831
DE CRÉCY-LAGARD V; MARLIERE P; SAURIN W, C R ACAD SCI III, vol. 318, 1995, pages 927 - 36
DU L; LOU L, NAT. PROD. REP., vol. 27, 2009, pages 255 - 78
EMMEL EA; VERWEIJ CL; DURAND DB; HIGGINS KM, SCIENCE, no. 246, 1989, pages 1617 - 1620
FUCHS SW; PROSCHAK A; JASKOLLA TW.; KARAS M; BODE HB, ORG BIOMOL CHEM, vol. 9, 2011, pages 3130 - 3132
FUCHS SW; SACHS CC; KEGLER C; NOLLMANN FI; KARAS M; BODE HB, ANALYTICAL CHEMISTRY, vol. 84, 2012, pages 6948
FUCHS SW; BOZHÜYÜK KA; KRESOVIC D; GRUNDMANN F; DILL V; BRACHMANN AO; WATERFIELD NR; BODE HB: "Angewandte Chemie", vol. 52, 2013, pages: 4108 - 4112
GAO, X.; HAYNES SW; AMES BD; WANG P; VIEN LP; WALSH CT; TANG Y, NAT. CHEM. BIOL., vol. 8, 2012, pages 823 - 830
GAUDELLI NM; TOWNSEND CA, NAT. CHEM. BIOL., vol. 10, 2014, pages 251 - 258
GIETZ RD; SCHIESTL RH, NAT PROTOC, vol. 2, 2007, pages 1 - 4
HARVEY AL; EDRADA-EBEL R; QUINN RJ, NAT REV DRUG DISCOV, vol. 14, 2015, pages 111 - 29
HAYNES SW; AMES BD; GAO X; TANG Y; WALSH CT, BIOCHEMISTRY, vol. 50, 2011, pages 5668 - 5679
HORSMAN ME; HARI TPA; BODDY CN, NAT. PROD. REP., 2015
ISHIZUKA M; TAKAYAMA H; TAKEUCHI T, J. ANTIBIOT., vol. 20, 1967, pages 15 - 24
KEATING TA; MARSHALL CG; WALSH CT; KEATING AE, NAT STRUCT BIOL., vol. 9, 2002, pages 522 - 6
KEGLER C; NOLLMANN FI; AHRENDT T; FLEISCHHACKER F; BODE E; BODE HB, CHEMBIOCHEM, vol. 15, 2014, pages 826
KOHLI RM; TRAUGER JW; SCHWARZER D; MARAHIEL MA; WALSH CT, BIOCHEMISTRY, vol. 40, 2001, pages 7099 - 7108
KOLB HC; SHARPLESS KB, DRUG DISCOV TODAY, vol. 8, 2003, pages 1128 - 37
KONZ, D.; KLENS, A.; SCHORGENDORFER, K.; MARAHIEL, M. A., CHEM BIOL, vol. 4, 1998, pages 927 - 937
KOPP F; MARAHIEL MA, NAT. PROD.RREP., vol. 24, 2007, pages 735 - 49
KORMAN TP; CRAWFORD JM; LABONTE JW; NEWMAN AG; WONG J; TOWNSEND CA; TSAI SC, PROC. NATL. ACAD. SCI. USA, vol. 107, 2010, pages 6246 - 6251
KRIES H; WACHTEL R; PABST A; WANNER B; NIQUILLE D; HILVERT D, ANGEW. CHEM. INT. ED., vol. 53, 2014, pages 10105 - 10108
KRONENWERTH M; BOZHÜYÜK KA; KAHNT AS; STEINHILBER D; GAUDRIAULT S; KAISER M; BODE HB, CHEMISTRY - A EUROPEAN JOURNAL, vol. 20, 2014, pages 17478 - 87
LEFEVRE F; ROBE P; JARRIN C; GINOLHAC A; ZAGO C; AURIOL D; VOGEL TM; SIMONET P; NALIN R, RES MICROBIOL, vol. 159, 2008, pages 153 - 61
LING LL; SCHNEIDER T; PEOPLES AJ; SPOERING AL, NATURE, vol. 517, 2015, pages 445 - 459
LOEFFLER W; TSCHEN J; VANITTANAKOM N, J. PHYTOPATHOL., vol. 115, 1986, pages 204 - 213
MARAHIEL MA, CHEM. BIOL., vol. 4, 1997, pages 561 - 567
MARAHIEL MA, NAT PROD REP, 2015
MEYER S; KEHR JC; MAINZ A; DEHM D; PETRAS D; SÜSSMUTH RD; DITTMANN E, CELL CHEM BIOL, vol. 23, 2016, pages 462 - 471
MITCHELL CA; SHI C; ALDRICH CC; GULICK AM, BIOCHEMISTRY, vol. 51, 2012, pages 3252 - 3263
NISHIHARA K; KANEMORI M; YANAGI H; YURA, T, APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 66, 2000, pages 884 - 889
NOLLMANN FI; DAUTH C; MULLEY G; KEGLER C; KAISER M; WATERFIELD NR; BODE HB, CHEMBIOCHEM, vol. 16, 2014, pages 205 - 8
LI R; OLIVER RA.; TOWNSEND CA, CELL CHEM BIOL, vol. 24, 2016, pages 24 - 34
PHELAN W; DU Y; MCLEAN JA; BACHMANN BO, CHEM BIOL., vol. 29, no. 16, 2009, pages 473 - 8
RAUSCH C; WEBER T; KOHLBACHER O; WOHLLEBEN W; HUSON DH, NUC. ACIDS. RES., vol. 33, 2005, pages 5799 - 5808
RAUSCH C; HOOF I; WEBER T; WOHLLEBEN W; HUSON DH, BMC EVOL BIOL., vol. 7, 2007, pages 78
REIMER D; COWLES KN; PROSCHAK A; NOLLMANN FI; DOWLING AJ; KAISER M; FFRENCH-CONSTANT R; GOODRICH-BLAIR H; BODE HB, CHEMBIOCHEM, vol. 14, 2013, pages 1991 - 1997
SAMEL SA; SCHOENAFINGER G; KNAPPE TA; MARAHIEL MA; ESSEN LO, STRUCTURE, vol. 15, 2007, pages 781 - 792
SCHIMMING O; FLEISCHHACKER F; NOLLMANN FI; BODE HB, CHEMBIOCHEM, vol. 15, 2014, pages 1290
SIEBER SA; MARAHIEL MA, CHEM. REV., vol. 105, 2005, pages 715 - 738
SLETTEN EM; BERTOZZI CR, ANGEW CHEM INT ED ENGL., vol. 48, 2009, pages 6974 - 98
SMITH S; TSAI S, NAT. PROD. REP., vol. 24, 2007, pages 1041 - 1072
STACHELHAUS T; SCHNEIDER A; MARAHIEL MA, SCIENCE, vol. 269, 1995, pages 69 - 72
STACHELHAUS T; MOOTZ HD; BERGENDAHL V; MARAHIEL MA, J BIOL CHEM., vol. 273, 1998, pages 22773 - 81
STACHELHAUS T; MOOTZ HD; MARAHIEL MA, CHEM. BIOL., vol. 6, 1999, pages 493 - 505
STRIEKER M; MARAHIEL MA, CURR. OPIN. STRUCT. BIOL., vol. 10, 2010, pages 234 - 240
SUNDLOV JA; GULICK AM, ACTA CRYSTALLOGR. D. BIOL. CRYSTALLOGR, vol. 6, 2013, pages 1482 - 1492
SÜSSMUTH RD; MAINZ A, ANGEW CHEM INT ED ENGL., vol. 56, 2017, pages 3770 - 3821
TAN XF; DAI YN; ZHOU K; JIANG YL; REN YM; CHEN Y; ZHOU CZ, ACTA CRYST, vol. D71, 2015, pages 873 - 881
TANOVIC A; SAMEL SA; ESSEN LO; MARAHIEL MA, SCIENCE, vol. 321, 2008, pages 659 - 663
TRAUGER JW; KOHLI RM; WALSH CT, NATURE, vol. 407, 2000, pages 215 - 218
TSENG CC; BRUNER SD; KOHLI RM; MARAHIEL MA; WALSH CT; SIEBER SA, BIOCHEMISTRY, vol. 41, 2002, pages 13350 - 13359
WINN, M; FYANS, JK; ZHUO Y; MICKLEFIELD J, NAT PROD REP, vol. 33, 2015, pages 317 - 347
Attorney, Agent or Firm:
KUTTENKEULER, David et al. (DE)
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