Title:
MICROORGANISMS FOR DITERPENE PRODUCTION
Document Type and Number:
WIPO Patent Application WO/2014/191581
Kind Code:
A3
Abstract:
The present invention relates to a recombinant microorganism comprising one or more nucleotide sequence(s) encoding: a polypeptide having ent-copalyl pyrophosphate synthase activity; a polypeptide having ent-Kaurene synthase activity; a polypeptide having ent-Kaurene oxidase activity; and a polypeptide having kaurenoic acid 13-hydroxylase activity, whereby expression of the nucleotide sequence(s) confer(s) on the microorganism the ability to produce at least steviol, and wherein said recombinant microorganism has been modified in its genome such that it results in a deficiency in the production of one or more of: (i) a phosphatase capable of acting on geranylgeranylpyrophosphate (GGPP) resulting in the formation of geranylgeraniol (GOH); (ii) a phosphatase capable of acting on farnesylpyrophosphate (FPP) resulting in the formation of farnesol and nerolidol; (iii) an exo-l,3-P glucanase; (iv) a glycogen synthase (or a polypeptide that influences glycogen accumulation); (v) a transcriptional repressor of hypoxic genes (ROX1) (vi) an NADPH oxidase; or (vii) a monocarboxylate transporter (JEN1) (viii) a polypeptide having activity as encoded for by the open reading frame, YJL064w; or (ix) a polypeptide having activity as encoded for by the open reading frame, YPL062w. The recombinant microorganism may also be capable of expressing one or more UDP-glucosyltransferases such that the microorganism is capable of producing one or more steviol glycosides.
Inventors:
BOER VIKTOR MARIUS (NL)
SUIR ERWIN (NL)
SUIR ERWIN (NL)
Application Number:
PCT/EP2014/061399
Publication Date:
March 05, 2015
Filing Date:
June 02, 2014
Export Citation:
Assignee:
DSM IP ASSETS BV (NL)
International Classes:
A23L2/60; A23L27/30; C07K14/39; C12P15/00; C07K14/395; C12N9/02; C12N9/10; C12N9/16; C12N9/24; C12N9/88; C12N9/90; C12N15/52; C12P19/56
Domestic Patent References:
| WO2013022989A2 | 2013-02-14 | |||
| WO2011153378A1 | 2011-12-08 | |||
| WO2012075030A1 | 2012-06-07 | |||
| WO2013110673A1 | 2013-08-01 |
Foreign References:
| US20070059790A1 | 2007-03-15 |
Other References:
GIONATA SCALCINATI ET AL: "Dynamic control of gene expression in Saccharomyces cerevisiae engineered for the production of plant sesquiterpene alpha-santalene in a fed-batch mode", METABOLIC ENGINEERING, vol. 14, no. 2, 8 February 2012 (2012-02-08), pages 91 - 103, XP028466089, ISSN: 1096-7176, DOI: 10.1016/J.YMBEN.2012.01.007
TOKUHIRO KENRO ET AL: "Overproduction of Geranylgeraniol by Metabolically Engineered Saccharomyces cerevisiae", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 75, no. 17, 10 July 2009 (2009-07-10), pages 5536 - 5543, XP002576694, ISSN: 0099-2240, DOI: 10.1128/AEM.00277-09
FAULKNER A ET AL: "THE LPP1 AND DPPP1 GENE PRODUCTS ACCOUNT FO RMOST OF THE ISOPRENOID PHSOPHATE PHOSPHATASE ACTIVITIES IN SACCHAROMYCES CEREVISIAE", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 21, 21 May 1999 (1999-05-21), pages 14831 - 14837, XP002908896, ISSN: 0021-9258, DOI: 10.1074/JBC.274.21.14831
OSHIRO J ET AL: "Diacylglycerol pyrophosphate phosphatase in Saccharomyces cerevisiae", BIOCHIMICA AND BIOPHYSICA ACTA, vol. 1635, no. 1, 30 November 2003 (2003-11-30), pages 1 - 9, XP004476013, ISSN: 1388-1981, DOI: 10.1016/J.BBALIP.2003.10.002
TOKE D A ET AL: "ISOLATION AND CHARACTERIZATION OF THE SACCHAROMYCES CEREVISIAE DPP1 GENE ENCODING DIACYLGLYCEROL PYROPHOSPHATE PHOSPHATASE", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 273, no. 6, 6 February 1998 (1998-02-06), pages 3278 - 3284, XP002908892, ISSN: 0021-9258, DOI: 10.1074/JBC.273.6.3278
HITESH KUMAR ET AL: "A comprehensive analysis of fifteen genes of steviol glycosides biosynthesis pathway in Stevia rebaudiana (Bertoni)", GENE, vol. 492, no. 1, 20 October 2011 (2011-10-20), pages 276 - 284, XP028345135, ISSN: 0378-1119, DOI: 10.1016/J.GENE.2011.10.015
BRANDLE ET AL: "Steviol glycoside biosynthesis", PHYTOCHEMISTRY, vol. 68, no. 14, 29 March 2007 (2007-03-29), pages 1855 - 1863, XP022145443, ISSN: 0031-9422, DOI: 10.1016/J.PHYTOCHEM.2007.02.010
NORIHIKO MISAWA: "Pathway engineering for functional isoprenoids", CURRENT OPINION IN BIOTECHNOLOGY, vol. 22, no. 5, 1 October 2011 (2011-10-01), pages 627 - 633, XP055012413, ISSN: 0958-1669, DOI: 10.1016/j.copbio.2011.01.002
I. FARKASS ET AL: "Two Glycogen Synthase Isoforms in Saccharomyces cerevisiae Are Coded by Distinct Genes That Are Differentially Controlled", J. BIOL. CHEM., vol. 266, no. 24, 25 August 1991 (1991-08-25), pages 15602 - 15607, XP055159777
JEAN FRANCOIS ET AL: "Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae", FEMS MICROBIOLOGY REVIEWS, vol. 25, 2001, pages 125 - 145, XP055159870
QUEIROZ-CLARET C ET AL: "Time-co-ordinated control of glycogen synthase, protein phosphatase 2A and protein kinase CK2 during culture growth in Yarrowia lipolytica in relation to glycogen metabolism", COMPTES RENDUS DES SEANCES DE L'ACADEMIE DES SCIENCES. SERIE III: SCIENCES DE LA VIE, vol. 323, no. 3, 1 March 2000 (2000-03-01), pages 257 - 266, XP004341533, ISSN: 0764-4469, DOI: 10.1016/S0764-4469(00)00127-X
TOKUHIRO KENRO ET AL: "Overproduction of Geranylgeraniol by Metabolically Engineered Saccharomyces cerevisiae", APPLIED AND ENVIRONMENTAL MICROBIOLOGY, vol. 75, no. 17, 10 July 2009 (2009-07-10), pages 5536 - 5543, XP002576694, ISSN: 0099-2240, DOI: 10.1128/AEM.00277-09
FAULKNER A ET AL: "THE LPP1 AND DPPP1 GENE PRODUCTS ACCOUNT FO RMOST OF THE ISOPRENOID PHSOPHATE PHOSPHATASE ACTIVITIES IN SACCHAROMYCES CEREVISIAE", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 274, no. 21, 21 May 1999 (1999-05-21), pages 14831 - 14837, XP002908896, ISSN: 0021-9258, DOI: 10.1074/JBC.274.21.14831
OSHIRO J ET AL: "Diacylglycerol pyrophosphate phosphatase in Saccharomyces cerevisiae", BIOCHIMICA AND BIOPHYSICA ACTA, vol. 1635, no. 1, 30 November 2003 (2003-11-30), pages 1 - 9, XP004476013, ISSN: 1388-1981, DOI: 10.1016/J.BBALIP.2003.10.002
TOKE D A ET AL: "ISOLATION AND CHARACTERIZATION OF THE SACCHAROMYCES CEREVISIAE DPP1 GENE ENCODING DIACYLGLYCEROL PYROPHOSPHATE PHOSPHATASE", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 273, no. 6, 6 February 1998 (1998-02-06), pages 3278 - 3284, XP002908892, ISSN: 0021-9258, DOI: 10.1074/JBC.273.6.3278
HITESH KUMAR ET AL: "A comprehensive analysis of fifteen genes of steviol glycosides biosynthesis pathway in Stevia rebaudiana (Bertoni)", GENE, vol. 492, no. 1, 20 October 2011 (2011-10-20), pages 276 - 284, XP028345135, ISSN: 0378-1119, DOI: 10.1016/J.GENE.2011.10.015
BRANDLE ET AL: "Steviol glycoside biosynthesis", PHYTOCHEMISTRY, vol. 68, no. 14, 29 March 2007 (2007-03-29), pages 1855 - 1863, XP022145443, ISSN: 0031-9422, DOI: 10.1016/J.PHYTOCHEM.2007.02.010
NORIHIKO MISAWA: "Pathway engineering for functional isoprenoids", CURRENT OPINION IN BIOTECHNOLOGY, vol. 22, no. 5, 1 October 2011 (2011-10-01), pages 627 - 633, XP055012413, ISSN: 0958-1669, DOI: 10.1016/j.copbio.2011.01.002
I. FARKASS ET AL: "Two Glycogen Synthase Isoforms in Saccharomyces cerevisiae Are Coded by Distinct Genes That Are Differentially Controlled", J. BIOL. CHEM., vol. 266, no. 24, 25 August 1991 (1991-08-25), pages 15602 - 15607, XP055159777
JEAN FRANCOIS ET AL: "Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae", FEMS MICROBIOLOGY REVIEWS, vol. 25, 2001, pages 125 - 145, XP055159870
QUEIROZ-CLARET C ET AL: "Time-co-ordinated control of glycogen synthase, protein phosphatase 2A and protein kinase CK2 during culture growth in Yarrowia lipolytica in relation to glycogen metabolism", COMPTES RENDUS DES SEANCES DE L'ACADEMIE DES SCIENCES. SERIE III: SCIENCES DE LA VIE, vol. 323, no. 3, 1 March 2000 (2000-03-01), pages 257 - 266, XP004341533, ISSN: 0764-4469, DOI: 10.1016/S0764-4469(00)00127-X
Attorney, Agent or Firm:
CHADWICK, Mark, Craig (P.O. Box 4, AA Echt, NL)
Download PDF:
Previous Patent: EXTRACELLULAR DITERPENE PRODUCTION
Next Patent: PROVISION OF A STATUS INDICATION TO A USER IN A VEHICLE COMMUNICATION SYSTEM
Next Patent: PROVISION OF A STATUS INDICATION TO A USER IN A VEHICLE COMMUNICATION SYSTEM