Title:
RECOMBINANT MICROORGANISMS FOR ENHANCED PRODUCTION OF MEVALONATE, ISOPRENE, AND ISOPRENOIDS
Document Type and Number:
WIPO Patent Application WO/2012/149491
Kind Code:
A3
Abstract:
The invention features compositions and methods for the increased production of mevalonate, isoprene, isoprenoid precursor molecules, and/or isoprenoids in microorganisms by engineering a microorganism for increased carbon flux towards mevalonate production in the following enzymatic pathways: (a) citrate synthase, (b) phosphotransacetylase, (c) acetate kinase, (d) lactate dehydrogenase, (e) malic enzyme, and (f) pyruvate dehydrogenase such that one of more of the enzyme activity is modulated. In addition, production of mevalonate, isoprene, isoprenoid precursor molecules, and/or isoprenoids can be further enhanced by the heterologous expression of the mvaE and mvaS genes (such as, but not limited to, mvaE and mvaS genes from the organisms Listeria grayi DSM 20601, Enterococcus faecium, Enterococcus gallinarum EG2, and Enterococcus casseliflavus).
Inventors:
BECK ZACHARY Q (US)
MILLER MICHAEL C (US)
PERES CAROLINE M (US)
PRIMAK YULIYA A (US)
PUCCI JEFF P (US)
WELLS DEREK H (US)
MILLER MICHAEL C (US)
PERES CAROLINE M (US)
PRIMAK YULIYA A (US)
PUCCI JEFF P (US)
WELLS DEREK H (US)
Application Number:
PCT/US2012/035687
Publication Date:
December 27, 2012
Filing Date:
April 27, 2012
Export Citation:
Assignee:
DANISCO US INC (US)
GOODYEAR TIRE & RUBBER (US)
BECK ZACHARY Q (US)
MILLER MICHAEL C (US)
PERES CAROLINE M (US)
PRIMAK YULIYA A (US)
PUCCI JEFF P (US)
WELLS DEREK H (US)
GOODYEAR TIRE & RUBBER (US)
BECK ZACHARY Q (US)
MILLER MICHAEL C (US)
PERES CAROLINE M (US)
PRIMAK YULIYA A (US)
PUCCI JEFF P (US)
WELLS DEREK H (US)
International Classes:
C12N1/21; C12N9/00; C12N9/10; C12N9/12; C12N9/18; C12N9/88; C12P5/00; C12P7/02; C12P7/04; C12P7/42
Domestic Patent References:
| WO2010148256A1 | 2010-12-23 | |||
| WO2010148150A1 | 2010-12-23 | |||
| WO2007140339A2 | 2007-12-06 | |||
| WO2010031077A1 | 2010-03-18 | |||
| WO2010078457A2 | 2010-07-08 | |||
| WO2009076676A2 | 2009-06-18 | |||
| WO2011079314A2 | 2011-06-30 | |||
| WO2000078935A1 | 2000-12-28 |
Foreign References:
| JP2008061506A | 2008-03-21 | |||
| EP1510583A1 | 2005-03-02 |
Other References:
W.R. FARMER ET AL: "Precursor Balancing for Metabolic Engineering of Lycopene Production in Escherichia coli", BIOTECHNOLOGY PROGRESS, vol. 17, no. 1, 2 February 2001 (2001-02-02), pages 57 - 61, XP055035828, ISSN: 8756-7938
R.V. VADALI ET AL: "Enhanced Lycopene Productivity by Manipulation of Carbon Flow to Isopentenyl Diphosphate in Escherichia coli", BIOTECHNOLOGY PROGRESS, vol. 21, no. 5, 7 October 2005 (2005-10-07), pages 1558 - 1561, XP055035831, ISSN: 8756-7938
HEMMI H ET AL: "IDENTIFICATION OF GENES AFFECTING LYCOPENE FORMATION IN ESCHERICHIA COLI TRANSFORMED WITH CAROTENOID BIOSYNTHETIC GENES: CANDIDATES FOR EARLY GENES IN ISOPRENOID BIOSYNTHESIS", JOURNAL OF BIOCHEMISTRY, vol. 123, no. 6, 1 June 1998 (1998-06-01), pages 1088 - 1096, XP001161200, ISSN: 0021-924X
TAO L ET AL: "Isolation of chromosomal mutations that affect carotenoid production in Escherichia coli: mutations alter copy number of ColE1-type plasmids", FEMS MICROBIOLOGY LETTERS, vol. 243, no. 1, 1 February 2005 (2005-02-01), pages 227 - 233, XP027871619, ISSN: 0378-1097
PITERA ET AL: "Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli", METABOLIC ENGINEERING, vol. 9, no. 2, 16 February 2007 (2007-02-16), pages 193 - 207, XP005888126, ISSN: 1096-7176
HISASHI HARADA ET AL: "Novel approaches and achievements in biosynthesis of functional isoprenoids in Escherichia coli", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, vol. 84, no. 6, 12 August 2009 (2009-08-12), pages 1021 - 1031, XP019757474, ISSN: 1432-0614
MIZIORKO ET AL: "Enzymes of the mevalonate pathway of isoprenoid biosynthesis", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 505, no. 2, 15 January 2011 (2011-01-15), pages 131 - 143, XP027587651, ISSN: 0003-9861
KAZUHIKO TABATA ET AL: "Production of mevalonate by a metabolically-engineered Escherichia coli", BIOTECHNOLOGY LETTERS, vol. 26, no. 19, 1 October 2004 (2004-10-01), pages 1487 - 1491, XP055013815, ISSN: 0141-5492
WILDING E I ET AL: "Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in gram-positive cocci", JOURNAL OF BACTERIOLOGY, vol. 182, no. 15, 1 August 2000 (2000-08-01), pages 4319 - 4327, XP002232852, ISSN: 0021-9193
SUZANNE M MA ET AL: "Optimization of a heterologous mevalonate pathway through the use of variant HMG-CoA reductases", METABOLIC ENGINEERING, vol. 13, no. 5, 13 July 2011 (2011-07-13), pages 588 - 597, XP028274826, ISSN: 1096-7176
R.V. VADALI ET AL: "Enhanced Lycopene Productivity by Manipulation of Carbon Flow to Isopentenyl Diphosphate in Escherichia coli", BIOTECHNOLOGY PROGRESS, vol. 21, no. 5, 7 October 2005 (2005-10-07), pages 1558 - 1561, XP055035831, ISSN: 8756-7938
HEMMI H ET AL: "IDENTIFICATION OF GENES AFFECTING LYCOPENE FORMATION IN ESCHERICHIA COLI TRANSFORMED WITH CAROTENOID BIOSYNTHETIC GENES: CANDIDATES FOR EARLY GENES IN ISOPRENOID BIOSYNTHESIS", JOURNAL OF BIOCHEMISTRY, vol. 123, no. 6, 1 June 1998 (1998-06-01), pages 1088 - 1096, XP001161200, ISSN: 0021-924X
TAO L ET AL: "Isolation of chromosomal mutations that affect carotenoid production in Escherichia coli: mutations alter copy number of ColE1-type plasmids", FEMS MICROBIOLOGY LETTERS, vol. 243, no. 1, 1 February 2005 (2005-02-01), pages 227 - 233, XP027871619, ISSN: 0378-1097
PITERA ET AL: "Balancing a heterologous mevalonate pathway for improved isoprenoid production in Escherichia coli", METABOLIC ENGINEERING, vol. 9, no. 2, 16 February 2007 (2007-02-16), pages 193 - 207, XP005888126, ISSN: 1096-7176
HISASHI HARADA ET AL: "Novel approaches and achievements in biosynthesis of functional isoprenoids in Escherichia coli", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, vol. 84, no. 6, 12 August 2009 (2009-08-12), pages 1021 - 1031, XP019757474, ISSN: 1432-0614
MIZIORKO ET AL: "Enzymes of the mevalonate pathway of isoprenoid biosynthesis", ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, vol. 505, no. 2, 15 January 2011 (2011-01-15), pages 131 - 143, XP027587651, ISSN: 0003-9861
KAZUHIKO TABATA ET AL: "Production of mevalonate by a metabolically-engineered Escherichia coli", BIOTECHNOLOGY LETTERS, vol. 26, no. 19, 1 October 2004 (2004-10-01), pages 1487 - 1491, XP055013815, ISSN: 0141-5492
WILDING E I ET AL: "Identification, evolution, and essentiality of the mevalonate pathway for isopentenyl diphosphate biosynthesis in gram-positive cocci", JOURNAL OF BACTERIOLOGY, vol. 182, no. 15, 1 August 2000 (2000-08-01), pages 4319 - 4327, XP002232852, ISSN: 0021-9193
SUZANNE M MA ET AL: "Optimization of a heterologous mevalonate pathway through the use of variant HMG-CoA reductases", METABOLIC ENGINEERING, vol. 13, no. 5, 13 July 2011 (2011-07-13), pages 588 - 597, XP028274826, ISSN: 1096-7176
Attorney, Agent or Firm:
SHIEH-NEWTON, Terri et al. (755 Page Mill RoadPalo Alto, CA, US)
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