公开(公告)号：WO2016007365A1

公开(公告)日：2016-01-14

申请号：PCT/US2015/038945

申请日：2015-07-02

Applicant: GENOMATICA, INC.

Inventor： PHARKYA, Priti ,  BURGARD, Anthony, P. ,  BURK, Mark, J.

IPC: C12N15/70 ,  C12P5/02 ,  C12N15/63 ,  C12N15/03

CPC classification number: C12P5/026 ,  C01B3/00 ,  C08F36/06 ,  C08F36/14 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/0067 ,  C12N9/10 ,  C12N9/12 ,  C12N15/52 ,  C12P3/00 ,  C12P7/40 ,  C12Y101/02007 ,  C12Y101/03013 ,  C12Y102/99003 ,  Y02E50/343

Abstract: The invention provides non-naturally occurring microbial organisms containing butadiene or 2,4- pentadienoate pathways comprising at least one exogenous nucleic acid encoding a butadiene or 2,4-pentadienoate pathway enzyme expressed in a sufficient amount to produce butadiene or 2,4-pentadienoate. The organism can further contain a hydrogen synthesis pathway. The invention additionally provides methods of using such microbial organisms to produce butadiene or 2,4-pentadienoate by culturing a non-naturally occurring microbial organism containing butadiene or 2,4-pentadienoate pathways as described herein under conditions and for a sufficient period of time to produce butadiene or 2,4-pentadienoate. Hydrogen can be produced together with the production of butadiene or 2,4- pentadienoate.

Abstract translation: 本发明提供了含有丁二烯或2,4-戊二烯酸通路的非天然存在的微生物生物，其包含至少一种编码丁二烯或2,4-戊二烯酸酯途径酶的外源核酸，其表达量足以产生丁二烯或2,4-戊二烯酸 。 生物体还可以含有氢合成途径。 本发明另外提供了使用这种微生物生物体来生产丁二烯或2,4-戊二烯酸盐的方法，其通过在条件和足够的时间段内培养含有本文所述的丁二烯或2,4-戊二烯酸酯途径的非天然存在的微生物生物 生产丁二烯或2,4-戊二烯酸。 可以与丁二烯或2,4-戊二烯酸2,4-二酮的生产一起生产氢。

公开(公告)号：WO2012177619A2

公开(公告)日：2012-12-27

申请号：PCT/US2012/043117

申请日：2012-06-19

Applicant: GENOMATICA, INC. ,  BURGARD, Anthony, P. ,  BURK, Mark, J. ,  OSTERHOUT, Robin, E. ,  SUN, Jun ,  PHARKYA, Priti

Inventor： BURGARD, Anthony, P. ,  BURK, Mark, J. ,  OSTERHOUT, Robin, E. ,  SUN, Jun ,  PHARKYA, Priti

IPC: C12N1/21 ,  C12P7/18

CPC classification number: C12P7/18 ,  C12N15/52

Abstract: Provided herein is a non-naturally occurring microbial organism having a 1,3-butanediol (1,3 -BDO) pathway and comprising at least one exogenous nucleic acid encoding a 1,3 -BDO pathway enzyme expressed in a sufficient amount to produce 1,3 -BDO. In some embodiments, the pathway includes reducing equivalents from CO or hydrogen. In certain embodiments, a 1,3-BDO pathway proceeds by way of central metabolites pyruvate, succinate or alpha-ketoglutarate. Also provided herein is a method for producing 1,3-BDO, includes culturing such microbial organisms under conditions and for a sufficient period of time to produce 1,3-BDO.

Abstract translation: 本文提供了具有1,3-丁二醇（1,3-BOD）途径的非天然存在的微生物生物，并且包含至少一种编码1,3 -BDO途径酶的外源核酸，其以足够的量表达以产生1 ，3 -BDO。 在一些实施方案中，该途径包括从CO或氢中还原当量。 在某些实施方案中，1,3-BDO途径通过中枢代谢物丙酮酸，琥珀酸或α-酮戊二酸进行。 本文还提供了一种生产1,3-BDO的方法，包括在条件和足够的时间内培养这些微生物以产生1,3-BDO。

公开(公告)号：WO2012135789A2

公开(公告)日：2012-10-04

申请号：PCT/US2012/031733

申请日：2012-03-30

Applicant: GENOMATICA, INC. ,  BURK, Mark, J. ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  SUN, Jun ,  PHARKYA, Priti

Inventor： BURK, Mark, J. ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  SUN, Jun ,  PHARKYA, Priti

IPC: C12P7/40

CPC classification number: C12P7/40 ,  C12P7/42 ,  C12P7/62 ,  C12P19/32

Abstract: The invention provides a non-naturally occurring microbial organism having a methacrylic acid, methacrylate ester, 3-hydroxyisobutyrate and/or 2-hydroxyisobutyrate pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in a methacrylic acid pathway. The invention additionally provides a method for producing methacrylic acid, methacrylate ester, 3-hydroxyisobutyrate and/or 2- hydroxyisobutyrate. The method can include culturing methacrylic acid, methacrylate ester, 3-hydroxyisobutyrate and/or 2-hydroxyisobutyrate producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a methacrylic acid pathway enzyme in a sufficient amount to produce methacrylic acid, methacrylate ester, 3-hydroxyisobutyrate and/or 2-hydroxyisobutyrate, under conditions and for a sufficient period of time to produce methacrylic acid, methacrylate ester, 3-hydroxyisobutyrate and/or 2-hydroxyisobutyrate.

Abstract translation: 本发明提供具有甲基丙烯酸，甲基丙烯酸酯，3-羟基异丁酸酯和/或2-羟基异丁酸酯途径的非天然存在的微生物生物。 微生物生物体含有编码甲基丙烯酸途径中的酶的至少一种外源核酸。 本发明另外提供了生产甲基丙烯酸，甲基丙烯酸酯，3-羟基异丁酸酯和/或2-羟基异丁酸酯的方法。 该方法可以包括培养产生甲基丙烯酸，甲基丙烯酸酯，3-羟基异丁酸酯和/或2-羟基异丁酸酯的微生物，其中微生物生物体表达至少一种编码甲基丙烯酸途径酶的外源核酸，其量足以产生甲基丙烯酸， 甲基丙烯酸酯，3-羟基异丁酸酯和/或2-羟基异丁酸酯在条件下和足够的时间以产生甲基丙烯酸，甲基丙烯酸酯，3-羟基异丁酸酯和/或2-羟基异丁酸酯。

公开(公告)号：WO2012018624A3

公开(公告)日：2012-02-09

申请号：PCT/US2011/045364

申请日：2011-07-26

Applicant: GENOMATICA, INC. ,  OSTERHOUT, Robin, E. ,  BURGARD, Anthony, P. ,  PHARKYA, Priti ,  BURK, Mark, J.

Inventor： OSTERHOUT, Robin, E. ,  BURGARD, Anthony, P. ,  PHARKYA, Priti ,  BURK, Mark, J.

IPC: C12P5/00 ,  C12P5/02 ,  C12P7/40

Abstract: The invention provides non-naturally occurring microbial organisms having a toluene, benzene, p-toluate, terephthalate, (2-hydroxy-3-methyl-4-oxobutoxy)phosphonate, (2-hydroxy-4-oxobutoxy)phosphonate, benzoate, styrene, 2,4-pentadienoate, 3-butene-lol or 1,3-butadiene pathway. The invention additionally provides methods of using such organisms to produce toluene, benzene, p-toluate, terephthalate, (2-hydroxy-3-methyl-4- oxobutoxy)phosphonate, (2-hydroxy-4-oxobutoxy)phosphonate, benzoate, styrene, 2,4- pentadienoate, 3-butene-lol or 1,3-butadiene.

公开(公告)号：WO2011017560A1

公开(公告)日：2011-02-10

申请号：PCT/US2010/044606

申请日：2010-08-05

Applicant: GENOMATICA, INC. ,  BURK, Mark, J. ,  OSTERHOUT, Robin, E. ,  SUN, Jun

Inventor： BURK, Mark, J. ,  OSTERHOUT, Robin, E. ,  SUN, Jun

IPC: C12N1/21 ,  C12P13/04 ,  C12P7/44

CPC classification number: C12P7/44 ,  C12N9/88 ,  C12Y402/01002

Abstract: The invention provides a non-naturally occurring microbial organism having a muconate pathway having at least one exogenous nucleic acid encoding a muconate pathway enzyme expressed in a sufficient amount to produce muconate. The muconate pathway including an enzyme selected from the group consisting of a beta-ketothiolase, a beta-ketoadipyl-CoA hydrolase, a beta-ketoadipyl-CoA transferase, a beta-ketoadipyl-CoA ligase, a 2- fumarylacetate reductase, a 2-fumarylacetate dehydrogenase, a trans -3-hydroxy-4- hexendioate dehydratase, a 2-fumarylacetate aminotransferase, a 2-fumarylacetate aminating oxidoreductase, a trans -3-amino-4-hexenoate deaminase, a beta-ketoadipate enol-lactone hydrolase, a muconolactone isomerase, a muconate cycloisomerase, a beta-ketoadipyl-CoA dehydrogenase, a 3-hydroxyadipyl-CoA dehydratase, a 2,3-dehydroadipyl-CoA transferase, a 2,3-dehydroadipyl-CoA hydrolase, a 2,3-dehydroadipyl-CoA ligase, a muconate reductase, a 2-maleylacetate reductase, a 2-maleylacetate dehydrogenase, a cis -3-hydroxy-4-hexendioate dehydratase, a 2-maleylacetate aminoatransferase, a 2-maleylacetate aminating oxidoreductase, a cis -3-amino-4-hexendioate deaminase, and a muconate cis/trans isomerase. Other muconate pathway enzymes also are provided. Additionally provided are methods of producing muconate.

Abstract translation: 本发明提供了一种非天然存在的微生物，其具有一种具有至少一种外源核酸的粘蛋白途径的微生物生物，所述外源核酸编码以足够量表达的粘蛋白途径酶以产生粘多糖。 粘膜途径包括选自β-酮硫解酶，β-酮己二酰辅酶A水解酶，β-酮己二酰辅酶A转移酶，β-酮己二酰辅酶A连接酶，2-富马酸乙酰酯还原酶，2- 富马酰乙酸脱氢酶，反式-3-羟基-4-己二酸脱水酶，2-富马酸乙酯氨基转移酶，2-富马酸乙酯胺化氧化还原酶，反式-3-氨基-4-己烯酸脱氨酶，β-酮己二酸烯醇内酯水解酶， 粘蛋白内酯异构酶，粘蛋白环异构酶，β-酮己二酰辅酶A脱氢酶，3-羟基己二酰辅酶A脱水酶，2,3-脱氢阿迪普基-CoA转移酶，2,3-脱氢阿迪普基-CoA水解酶，2,3-脱氢阿迪普酯 - CoA连接酶，粘蛋白还原酶，2-马来酰乙酸酯还原酶，2-马来酰乙酸酯脱氢酶，顺式-3-羟基-4-己二酸脱水酶，2-马来酰乙酸酯氨基转移酶，2-马来酰乙酸胺胺化氧化还原酶，顺式-3-氨基 -4-十六酸脱氨酶和粘蛋白顺式/反式异构酶。 还提供了其它粘蛋白途径酶。 另外提供了生产粘蛋白的方法。

公开(公告)号：WO2010141920A2

公开(公告)日：2010-12-09

申请号：PCT/US2010/037544

申请日：2010-06-04

Applicant: GENOMATICA, INC. ,  VAN DIEN, Stephen, J. ,  BURGARD, Anthony, P. ,  HASELBECK, Robert ,  PUJOL-BAXLEY, Catherine, J. ,  NIU, Wei ,  TRAWICK, John, D. ,  YIM, Harry ,  BURK, Mark, J. ,  OSTERHOUT, Robin, E. ,  SUN, Jun

Inventor： VAN DIEN, Stephen, J. ,  BURGARD, Anthony, P. ,  HASELBECK, Robert ,  PUJOL-BAXLEY, Catherine, J. ,  NIU, Wei ,  TRAWICK, John, D. ,  YIM, Harry ,  BURK, Mark, J. ,  OSTERHOUT, Robin, E. ,  SUN, Jun

IPC: C12P7/18

CPC classification number: C12P7/18 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/001 ,  C12N9/13 ,  C12N9/16 ,  C12N9/88 ,  C12N9/93 ,  C12N15/52

Abstract: The invention provides non-naturally occurring microbial organisms comprising a 1,4-butanediol (BDO) pathway comprising at least one exogenous nucleic acid encoding a BDO pathway enzyme expressed in a sufficient amount to produce BDO and further optimized for expression of BDO. The invention additionally provides methods of using such microbial organisms to produce BDO.

Abstract translation: 本发明提供包含1,4-丁二醇（BDO）途径的非天然存在的微生物生物，其包含至少一种编码足够量的BDO途径酶的外源核酸以产生BDO并进一步优化BDO的表达。 本发明还提供了使用这种微生物生产BDO的方法。

公开(公告)号：WO2010132845A1

公开(公告)日：2010-11-18

申请号：PCT/US2010/035015

申请日：2010-05-14

Applicant: GENOMATICA, INC. ,  OSTERHOUT, Robin, E. ,  BURGARD, Anthony, P. ,  BURK, Mark, J. ,  PHARKYA, Priti

Inventor： OSTERHOUT, Robin, E. ,  BURGARD, Anthony, P. ,  BURK, Mark, J. ,  PHARKYA, Priti

IPC: A61K48/00 ,  C07C49/00

CPC classification number: C12P7/26 ,  C12N9/16 ,  C12N9/88 ,  C12N9/93 ,  C12N15/52 ,  C12N15/70

Abstract: A non-naturally occurring microbial organism has cyclohexanone pathways that include at least one exogenous nucleic acid encoding a cyclohexanone pathway enzyme. A pathway includes a 2-ketocyclohexane-1 -carboxyl-CoA hydrolase (acting on C-C bond), a 2-ketocyclohexane-l- carboxylate decarboxylase and an enzyme selected from a 2-ketocyclohexane-l-carboxyl-CoA hydrolase (acting on thioester), a 2-ketocyclohexane-l -carboxyl-CoA transferase, and a 2- ketocyclohexane-1-carboxyl-CoA synthetase. A pathway includes an enzyme selected from a 6- ketocyclohex-1-ene-l-carboxyl-CoA hydrolase (acting on C-C bond), a 6-ketocyclohex- 1 -ene- 1 - carboxyl-CoA synthetase, a 6-ketocyclohex-l-ene-l-carboxyl-CoA hydrolase (acting on thioester), a 6-ketocyclohex- 1 -ene- 1 -carboxyl-CoA transferase, a 6-ketocyclohex- 1 -ene- 1 - carboxyl-CoA reductase, a 6-ketocyclohex- 1 -ene- 1 -carboxylate decarboxylase, a 6- ketocyclohex-1 -ene- 1 -carboxylate reductase, a 2-ketocyclohexane-l-carboxyl-CoA synthetase, a 2-ketocyclohexane-l -carboxyl-CoA transferase, a 2-ketocyclohexane-l-carboxyl-CoA hydrolase (acting on thioester), a 2-ketocyclohexane-l -carboxylate decarboxylase, and a cyclohexanone dehydrogenase. A pathway includes an adipate semialdehyde dehydratase, a cyclohexane-1,2- diol dehydrogenase, and a cyclohexane-l,2-diol dehydratase. A pathway includes a 3- oxopimelate decarboxylase, a 4-acetylbutyrate dehydratase, a 3-hydroxycyclohexanone dehydrogenase, a 2-cyclohexenone hydratase, a cyclohexanone dehydrogenase and an enzyme selected from a 3-oxopimeloyl-CoA synthetase, a 3-oxopimeloyl-CoA hydrolase (acting on thioester), and a 3-oxopimeloyl-coA transferase. Each these pathways can include a PEP carboxykinase. A method for producing cyclohexanone includes culturing these non-naturally occurring microbial organisms.

Abstract translation: 非天然存在的微生物有机体具有包含至少一种编码环己酮途径酶的外源核酸的环己酮途径。 途径包括2-酮环己烷-1-羧基-CoA水解酶（作用于CC键），2-酮环己烷-1-羧酸脱羧酶和选自2-酮环己烷-1-羧基-CoA水解酶（酶作用于硫酯） ），2-酮环己烷-1-羧基-CoA转移酶和2-酮环己烷-1-羧基-CoA合成酶。 途径包括选自6-酮环己-1-烯-1-羧基-CoA水解酶（作用于CC键）的酶，6-酮环己-1-烯-1-羧基-CoA合成酶，6-酮环己基 - 1-烯-1-羧基-CoA水解酶（作用于硫酯），6-酮环己-1-烯-1-羧基-CoA转移酶，6-酮环己-1-烯-1-羧基-CoA还原酶，6 2-环己-1-烯-1-羧酸脱羧酶，6-酮环己-1-烯-1-羧酸还原酶，2-酮环己烷-1-羧基-CoA合成酶，2-酮环己烷-1-羧基-CoA转移酶， 2-酮环己烷-1-羧基-CoA水解酶（作用于硫酯），2-酮环己烷-1-羧酸脱羧酶和环己酮脱氢酶。 途径包括己二酸半醛脱水酶，环己烷-1,2-二醇脱氢酶和环己烷-1,2-二醇脱水酶。 途径包括3-氧代庚酸酯脱羧酶，4-乙酰基丁酸脱水酶，3-羟基环己酮脱氢酶，2-环己烯酮水合酶，环己酮脱氢酶和选自3-氧代木糖酰辅酶A合成酶，3-氧代木糖酰-CoA水解酶 （作用于硫酯）和3-氧代木糖酰辅酶A转移酶。 每个这些途径可以包括PEP羧基激酶。 生产环己酮的方法包括培养这些非天然存在的微生物。

公开(公告)号：WO2011066076A1

公开(公告)日：2011-06-03

申请号：PCT/US2010/055524

申请日：2010-11-04

Applicant: GENOMATICA, INC. ,  SUN, Jun ,  BURK, Mark, J. ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  NIU, Wei ,  TRAWICK, John, D. ,  HASELBECK, Robert

Inventor： SUN, Jun ,  BURK, Mark, J. ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  NIU, Wei ,  TRAWICK, John, D. ,  HASELBECK, Robert

IPC: C12P7/38 ,  C12P7/16 ,  C12N1/20

CPC classification number: C12P17/04 ,  C12N1/20 ,  C12N15/52 ,  C12P7/18

Abstract: The invention provides non-naturally occurring microbial organisms comprising 1,4- butanediol (14-BDO) and gamma-butyrolactone (GBL) pathways comprising at least one exogenous nucleic acid encoding a 14-BDO and GBL pathway enzyme expressed in a sufficient amount to produce 14-BDO and GBL. The invention additionally provides methods of using such microbial organisms to produce 14-BDO and GBL.

Abstract translation: 本发明提供包含1,4-丁二醇（14-BDO）和γ-丁内酯（GBL）途径的非天然存在的微生物生物，其包含至少一种编码14-BDO和GBL途径酶的外源核酸，其以足够的量表达， 生产14-BDO和GBL。 本发明另外提供了使用这种微生物生物来生产14-BDO和GBL的方法。

公开(公告)号：WO2011031897A1

公开(公告)日：2011-03-17

申请号：PCT/US2010/048318

申请日：2010-09-09

Applicant: GENOMATICA, INC. ,  PHARKYA, Priti ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  BURK, Mark, J. ,  SUN, Jun

Inventor： PHARKYA, Priti ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  BURK, Mark, J. ,  SUN, Jun

IPC: C12P7/04 ,  C12N15/74

CPC classification number: C12P7/40 ,  C12N15/52 ,  C12P7/04 ,  C12P7/18

Abstract: The invention provides a non-naturally occurring microbial organism having n-propanol and isopropanol pathways, 1,4-butanediol (14-BDO) and isopropanol pathways, 1,3-butanediol (13- BDO) and isopropanol pathways or methylacrylic acid (MAA) and isopropanolpathways. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in each of the respective n-propanol, 14-BDO, 13-BDO or MAA and isopropanol pathways. The invention additionally provides a method for co-producing n-propanol and isopropanol, 14-BDO and isopropanol, 13-BDO and isopropanol or MAA and isopropanol. The method can include culturing an n-propanol and an isopropanol co-producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an n-propanol, an isopropanol, a 14-BDO, a 13-BDO and/or a MAA pathway enzyme in a sufficient amount to produce each of the respective products, under conditions and for a sufficient period of time to produce each of the respective products.

Abstract translation: 本发明提供具有正丙醇和异丙醇途径的非天然存在的微生物生物，1,4-丁二醇（14-BDO）和异丙醇途径，1,3-丁二醇（13-BDO）和异丙醇途径或甲基丙烯酸（MAA ）和异丙醇通道。 微生物生物体含有至少一种外源核酸，其编码在各自的正丙醇，14-BDO，13-BDO或MAA和异丙醇途径中的酶。 本发明另外提供了共同生产正丙醇和异丙醇，14-BDO和异丙醇，13-BDO和异丙醇或MAA和异丙醇的方法。 该方法可以包括培养正丙醇和异丙醇共同生产微生物，其中微生物生物体表达至少一种编码正丙醇，异丙醇，14-BDO，13-BDO和/或 足够量的MAA途径酶，以在产生各个产物的条件下和足够的时间段内产生各个产物。

公开(公告)号：WO2010129936A1

公开(公告)日：2010-11-11

申请号：PCT/US2010/034144

申请日：2010-05-07

Applicant: GENOMATICA, INC. ,  BURK, Mark, J. ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  PHARKYA, Priti

Inventor： BURK, Mark, J. ,  BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  PHARKYA, Priti

IPC: C12N1/21 ,  C12P13/04 ,  C12P7/44

CPC classification number: C12P17/10 ,  C12N1/38 ,  C12N15/52 ,  C12P7/40 ,  C12P7/44 ,  C12P13/001 ,  C12P13/005 ,  C12P13/02 ,  C12P17/12

Abstract: The invention provides a non-naturally occurring microbial organism having a 6- aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The microbial organism contains at least one exogenous nucleic acid encoding an enzyme in the respective 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway. The invention additionally provides a method for producing 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid. The method can include culturing a 6-aminocaproic acid, caprolactam or hexametheylenediamine producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding a 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid pathway enzyme in a sufficient amount to produce the respective product, under conditions and for a sufficient period of time to produce 6-aminocaproic acid, caprolactam, hexametheylenediamine or levulinic acid.

Abstract translation: 本发明提供了具有6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸途径的非天然存在的微生物。 微生物生物体含有至少一种编码各自的6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸途径中的酶的外源核酸。 本发明另外提供了制备6-氨基己酸，己内酰胺，己二胺或乙酰丙酸的方法。 该方法可以包括培养6-氨基己酸，己内酰胺或六亚甲基二胺生产微生物，其中微生物生物表达至少一种编码6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸途径酶的外源核酸，其量足以产生 各自的产物在条件下和足够的时间内产生6-氨基己酸，己内酰胺，六亚甲基二胺或乙酰丙酸。