公开(公告)号：WO2010144746A2

公开(公告)日：2010-12-16

申请号：PCT/US2010/038230

申请日：2010-06-10

Applicant: GENOMATICA, INC. ,  OSTERHOUT, Robin, E. ,  NIU, Wei ,  BURGARD, Anthony, P.

Inventor： OSTERHOUT, Robin, E. ,  NIU, Wei ,  BURGARD, Anthony, P.

IPC: C12P7/26 ,  C12N1/00 ,  C12P7/16

CPC classification number: C12P7/26 ,  C12N15/52 ,  C12P7/16 ,  Y02E50/10

Abstract: A non-naturally occurring microbial organism has at least one exogenous nucleic acid encoding a MEK pathway enzyme expressed in a sufficient amount to produce MEK. The MEK pathway includes an enzyme selected from an acetoacetyl-CoA dehydrogenase (bifunctional), an acetoacetyl-CoA aldehyde dehydrogenase, a 3-oxobutyraldehyde reductase, a 3-oxobutanol dehydratase, an MEK oxidoreductase, a 3-oxobutyraldehyde aminotransferase, a 4-aminobutan-2-one deaminase, a 2-amino-4-ketopentanoate (AKP) thiolase, an AKP aminotransferase, a 2,4-dioxopentanoate decarboxylase, an AKP deaminase, an acetylacrylate decarboxylase, an AKP decarboxylase, a glutamate dehydrogenase, a 3-oxobutyraldehyde oxidoreductase (aminating) and an AKP oxidoreductase (aminating). A 2-butanol pathway further includes an MEK reductase. A method for producing MEK or 2-butanol includes culturing these organisms under conditions and for a sufficient period of time to produce MEK or 2-butanol.

Abstract translation: 非天然存在的微生物有至少一种编码MEK途径酶的外源核酸，其表达量足以产生MEK。 MEK途径包括选自乙酰乙酰辅酶A脱氢酶（双功能），乙酰乙酰辅酶A醛脱氢酶，3-氧代丁醛还原酶，3-氧代丁醇脱水酶，MEK氧化还原酶，3-氧代丁醛氨基转移酶，4-氨基丁酸 -2-酮脱氨酶，2-氨基-4-酮戊酸酯（AKP）硫解酶，AKP氨基转移酶，2,4-二氧代戊酸脱羧酶，AKP脱氨酶，乙酰丙酸酯脱羧酶，AKP脱羧酶，谷氨酸脱氢酶， 氧化丁醛氧化还原酶（胺化）和AKP氧化还原酶（胺化）。 2-丁醇途径还包括MEK还原酶。 包括生产MEK或2-丁醇的方法包括在条件和足够的时间内培养这些生物体以产生MEK或2-丁醇。

公开(公告)号：WO2010127319A2

公开(公告)日：2010-11-04

申请号：PCT/US2010/033300

申请日：2010-04-30

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

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

IPC: C12N1/21 ,  C12P7/18

CPC classification number: C12P7/18 ,  C07C29/80 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/1029 ,  C12N9/1096 ,  C12N9/88 ,  C12N15/52 ,  C12Y101/01 ,  C12Y101/01157 ,  C12Y102/01 ,  C12Y203/01 ,  C12Y206/01 ,  C12Y401/01 ,  C12Y402/01 ,  C12Y403/01

Abstract: A non-naturally occurring microbial organism includes a microbial organism having a 1,3-butanediol (1,3-BDO) pathway having at least one exogenous nucleic acid encoding a 1,3- BDO pathway enzyme expressed in a sufficient amount to produce 1,3-BDO. The pathway includes an enzyme selected from a 2-amino-4-ketopentanoate (AKP) thiolase, an AKP dehydrogenase, a 2-amino-4-hydroxypentanoate aminotransferase, a 2-amino-4- hydroxypentanoate oxidoreductase (deaminating), a 2-oxo-4-hydroxypentanoate decarboxylase, a 3-hydroxybutyraldehyde reductase, an AKP aminotransferase, an AKP oxidoreductase (deaminating), a 2,4-dioxopentanoate decarboxylase, a 3-oxobutyraldehyde reductase (ketone reducing), a 3-oxobutyraldehyde reductase (aldehyde reducing), a 4-hydroxy-2-butanone reductase, an AKP decarboxylase, a 4-aminobutan-2-one aminotransferase, a 4-aminobutan-2- one oxidoreductase (deaminating), a 4-aminobutan-2-one ammonia-lyase, a butenone hydratase, an AKP ammonia-lyase, an acetylacrylate decarboxylase, an acetoacetyl-CoA reductase (CoA- dependent, aldehyde forming), an acetoacetyl-CoA reductase (CoA-dependent, alcohol forming), an acetoacetyl-CoA reductase (ketone reducing), a 3-hydroxybutyryl-CoA reductase (aldehyde forming), a 3-hydroxybutyryl-CoA reductase (alcohol forming), a 4-hydroxybutyryl- CoA dehydratase, and a crotonase. 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: 非天然存在的微生物有机体包括具有1,3-丁二醇（1,3-BDO）途径的微生物，其具有至少一种编码1,3-BDO途径酶的外源核酸 以足以产生1,3-BDO的量表达。 该途径包括选自2-氨基-4-酮戊酸（AKP）硫解酶，AKP脱氢酶，2-氨基-4-羟基戊酸氨基转移酶，2-氨基-4-羟基戊酸酯氧化还原酶（脱氨基），2-氨基-4-羟基戊酸 4-羟基戊酸脱羧酶，3-羟基丁醛还原酶，AKP氨基转移酶，AKP氧化还原酶（脱氨基），2,4-二氧代戊酸脱羧酶，3-氧代丁醛还原酶（酮还原），3-氧代丁醛还原酶（醛还原 ），4-羟基-2-丁酮还原酶，AKP脱羧酶，4-氨基丁-2-酮转氨酶，4-氨基丁-2-酮氧化还原酶（脱氨基），4-氨基丁-2-酮氨裂解酶 ，丁烯酮水合酶，AKP氨 - 裂解酶，乙酰基丙烯酸酯脱羧酶，乙酰乙酰-CoA还原酶（CoA依赖性，醛形成），乙酰乙酰-CoA还原酶（CoA依赖性，形成醇），乙酰乙酰-CoA还原酶（酮 还原），3-羟基丁酰-CoA还原酶（醛形成），3-羟基 乌乙酰-CoA还原酶（形成醇），4-羟基丁酰-CoA脱水酶和巴豆酸酶。 生产1,3-BDO的方法包括在一定条件下培养这种微生物并持续足够的时间以产生1,3-BDO。

公开(公告)号：WO2015084633A1

公开(公告)日：2015-06-11

申请号：PCT/US2014/067287

申请日：2014-11-25

Applicant: GENOMATICA, INC.

Inventor： OSTERHOUT, Robin, E. ,  BURGARD, Anthony, P. ,  PHARKYA, Priti ,  ANDRAE, Stefan

IPC: C12N1/19 ,  C12N1/15 ,  C12N1/13 ,  C12N1/11

CPC classification number: C12P5/026 ,  C12N1/14 ,  C12N1/20 ,  C12N15/70 ,  C12N15/81 ,  C12P7/02 ,  C12P7/04 ,  C12P7/18 ,  C12P7/40 ,  C12P7/42 ,  C12P7/44 ,  C12P13/001 ,  C12P13/005 ,  C12P17/10 ,  Y02E50/343

Abstract: The invention provides non-naturally occurring microbial organisms containing enzymatic pathways and/or metabolic modifications for enhancing carbon flux through acetyl-CoA. In some embodiments, the microbial organisms having such pathways also include pathways for generating reducing equivalents, formaldehyde fixation and/or formate assimilation. The enhanced carbon flux through acetyl-CoA, in combination with pathways for generating reducing equivalents, formaldehyde fixation and/or formate assimilation can, in some embodiments, be used for production of a bioderived compound. Accordingly, in some embodiments, the microbial organisms of the invention can include a pathway capable of producing a bioderived compound of the invention. The invention still further provides a bioderived compound produced by a microbial organism of the invention, culture medium having the bioderived compound of the invention, compositions having the bioderived compound of the invention, a biobased product comprising the bioderived compound of the invention, and a process for producing a bioderived compound of the invention.

Abstract translation: 本发明提供了非天然存在的微生物，其含有通过乙酰辅酶A的碳通量的酶途径和/或代谢修饰。 在一些实施方案中，具有这种途径的微生物生物体还包括产生还原当量的途径，甲醛固定和/或甲酸盐同化。 在一些实施方案中，通过乙酰辅酶A增强的碳通量与产生还原当量的途径，甲醛固定和/或甲酸盐同化可用于生产生物活性化合物。 因此，在一些实施方案中，本发明的微生物体可以包括能够产生本发明生物活性化合物的途径。 本发明还提供了由本发明的微生物生物产生的生物活性化合物，具有本发明的生物活性化合物的培养基，具有本发明的生物活性化合物的组合物，包含本发明的生物活性化合物的生物基产物和一种方法 用于生产本发明的生物活性化合物。

公开(公告)号：WO2014152434A2

公开(公告)日：2014-09-25

申请号：PCT/US2014/027337

申请日：2014-03-14

Applicant: GENOMATICA, INC.

Inventor： BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  PHARKYA, Priti ,  ANDRAE, Stefan ,  LIS, Ewa, T. ,  RISSO, Carla ,  TRAWICK, John, D.

IPC: A61B17/70

CPC classification number: C12N15/63 ,  C07C1/24 ,  C07C11/167 ,  C07C31/207 ,  C07C33/025 ,  C07K14/195 ,  C09D147/00 ,  C09J147/00 ,  C12N9/1022 ,  C12N9/88 ,  C12N9/90 ,  C12N15/52 ,  C12P5/026 ,  C12P7/04 ,  C12P7/18 ,  Y02E50/343

Abstract: Provided herein are non-naturally occurring microbial organisms having a FaldFP, a FAP and/or metabolic modifications which can further include a MMP, a MOP, a hydrogenase and/or a CODH. These microbial organisms can further include a butadiene, 13BDO, CrotOH, MVC or 3-buten-1-ol pathway. Additionally provided are methods of using such microbial organisms to produce butadiene, 13BDO, CrotOH, MVC or 3-buten-1-ol.

Abstract translation: 本文提供了具有FaldFP，FAP和/或可进一步包含MMP，MOP，氢化酶和/或CODH的代谢修饰的非天然存在的微生物生物体。 这些微生物可以进一步包括丁二烯，13BDO，CrotOH，MVC或3-丁烯-1-醇途径。 另外提供了使用这些微生物生产丁二烯，13BDO，CrotOH，MVC或3-丁烯-1-醇的方法。

公开(公告)号：WO2014106122A1

公开(公告)日：2014-07-03

申请号：PCT/US2013/078117

申请日：2013-12-27

Applicant: GENOMATICA, INC.

Inventor： BURK, Mark, J. ,  OSTERHOUT, Robin, E. ,  TORCHIA, Timothy, E. ,  TRACEWELL, Cara, Ann ,  KHANDURINA, Julia

IPC: C12P5/02 ,  C12M1/34

CPC classification number: C12P5/026 ,  Y02E50/343

Abstract: In alternative embodiments, the invention provides compositions and methods for the detection of organisms having butadiene biosynthetic capability. In alternative embodiments, the invention provides high-throughput detection methods of products of biosynthetic processes, more specifically to detection of organisms having or having improved butadiene biosynthetic capability. In alternative embodiments, the invention provides compositions and methods for screening or assaying a population of cells for: the production of a butadiene; or, for the rate of production of a butadiene; or, for the improved production of a butadiene.

Abstract translation: 在替代实施方案中，本发明提供了用于检测具有丁二烯生物合成能力的生物体的组合物和方法。 在替代实施方案中，本发明提供生物合成方法产物的高通量检测方法，更具体地，涉及具有或具有改进的丁二烯生物合成能力的生物体的检测。 在替代实施方案中，本发明提供用于筛选或测定细胞群的组合物和方法，用于：生产丁二烯; 或者，对于丁二烯的生产速率; 或者为了改进丁二烯的生产。

公开(公告)号：WO2014099725A1

公开(公告)日：2014-06-26

申请号：PCT/US2013/075287

申请日：2013-12-16

Applicant: GENOMATICA, INC.

Inventor： BURGARD, Anthony, P. ,  OSTERHOUT, Robin, E. ,  VAN DIEN, Stephen, J. ,  TRACEWELL, Cara, Ann ,  PHARKYA, Priti ,  ANDRAE, Stefan

IPC: C12N1/21

CPC classification number: C12P17/10 ,  A23L29/065 ,  C08G63/78 ,  C08G69/08 ,  C08G69/16 ,  C08G73/0213 ,  C12N9/0006 ,  C12N15/52 ,  C12P7/24 ,  C12P7/44 ,  C12P13/001 ,  C12P13/005 ,  C12Y101/01244

Abstract: Provided herein is a non-naturally occurring microbial organism having a methanol metabolic pathway that can enhance the availability of reducing equivalents in the presence of methanol. Such reducing equivalents can be used to increase the product yield of organic compounds produced by the microbial organism, such as adipate, 6-aminocaproate, hexamethylenediamine or caprolactam. Also provided herein are methods for using such an organism to produce adipate, 6-aminocaproate, hexamethylenediamine or caprolactam.

Abstract translation: 本文提供了具有甲醇代谢途径的非天然存在的微生物生物，其可以在甲醇存在下增强还原当量的可用性。 这样的还原当量可用于增加微生物生物体如己二酸，6-氨基己酸，六亚甲基二胺或己内酰胺产生的有机化合物的产物产率。 本文还提供了使用这种生物体产生己二酸，6-氨基己酸，六亚甲基二胺或己内酰胺的方法。

公开(公告)号：WO2013067432A1

公开(公告)日：2013-05-10

申请号：PCT/US2012/063424

申请日：2012-11-02

Applicant: GENOMATICA, INC.

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

IPC: C12P17/02

CPC classification number: C12P17/08 ,  C07D313/04 ,  C08G18/4277 ,  C08G63/08 ,  C12N5/0018 ,  C12N15/52 ,  C12N15/63 ,  C12N15/70 ,  C12P17/02

Abstract: The invention provides non-naturally occurring microbial organisms containing caprolactone pathways having at least one exogenous nucleic acid encoding a butadiene pathway enzyme expressed in a sufficient amount to produce caprolactone. The invention additionally provides methods of using such microbial organisms to produce caprolactone by culturing a non-naturally occurring microbial organism containing caprolactone pathways as described herein under conditions and for a sufficient period of time to produce caprolactone.

Abstract translation: 本发明提供了含有己内酯途径的非天然存在的微生物，其具有至少一种编码丁二烯途径酶的外源核酸，其以足够的量表达以产生己内酯。 本发明另外提供了使用这种微生物生物体制备己内酯的方法，通过在条件和足够的时间内培养含有本文所述的己内酯途径的非天然存在的微生物生物体以制备己内酯。

公开(公告)号：WO2013036764A1

公开(公告)日：2013-03-14

申请号：PCT/US2012/054152

申请日：2012-09-07

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

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

IPC: C12P7/04 ,  C12P1/00

CPC classification number: C12N15/52 ,  C08G63/16 ,  C12N1/14 ,  C12N1/16 ,  C12N1/20 ,  C12P7/18 ,  C12P19/32

Abstract: Provided herein are non-naturally occurring eukaryotic organisms that can be engineered to produce and increase the availability of cytosolic acetyl-CoA. Also provided herein are non-naturally occurring eukaryotic organisms having a 1,3-butanediol (1,3-BDO) pathway, and methods of using such organisms to produce 1,3-BDO.

Abstract translation: 本文提供了非天然存在的真核生物，其可被工程化以产生和增加细胞溶质乙酰辅酶A的可用性。 本文还提供具有1,3-丁二醇（1,3-BDO）途径的非天然存在的真核生物，以及使用这些生物体产生1,3-BDO的方法。

公开(公告)号：WO2013028519A1

公开(公告)日：2013-02-28

申请号：PCT/US2012/051347

申请日：2012-08-17

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

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

IPC: C12P7/18

CPC classification number: C12P7/16 ,  C12N15/70 ,  C12P5/026 ,  C12P7/04 ,  C12P7/18 ,  C12P7/40 ,  Y02E50/10

Abstract: The invention provides non-naturally occurring microbial organisms containing 2,4-pentadienoate, butadiene, propylene, 1,3-butanediol, crotyl alcohol or 3-buten-1-ol pathways comprising at least one exogenous nucleic acid encoding a butadiene pathway enzyme expressed in a sufficient amount to produce 2,4-pentadienoate, butadiene, propylene, 1,3-butanediol, crotyl alcohol or 3-buten-1-ol. The invention additionally provides methods of using such microbial organisms to produce 2,4-pentadienoate, butadiene, propylene, 1,3-butanediol, crotyl alcohol or 3-buten-1-ol, by culturing a non- naturally occurring microbial organism containing 2,4-pentadienoate, butadiene, propylene, 1,3-butanediol, crotyl alcohol or 3-buten-l-ol pathways as described herein under conditions and for a sufficient period of time to produce 2,4-pentadienoate, butadiene, propylene, 1,3-butanediol, crotyl alcohol or 3-buten-1-ol.

Abstract translation: 本发明提供包含2,4-戊二烯酸，丁二烯，丙烯，1,3-丁二醇，巴豆醇或3-丁烯-1-醇途径的非天然存在的微生物生物体，其包含至少一种外源性 编码丁二烯途径酶的核酸，其表达量足以产生2,4-戊二烯酸，丁二烯，丙烯，1,3-丁二醇，巴豆醇或3-丁烯-1-醇。 本发明另外提供了通过培养含有2个非天然存在的微生物的微生物来生产2,4-戊二烯酸，丁二烯，丙烯，1,3-丁二醇，巴豆醇或3-丁烯-1-醇的方法 ，4-戊二烯酸酯，丁二烯，丙烯，1,3-丁二醇，巴豆醇或3-丁烯-1-醇途径在一定条件下和足够的时间内生成2,4-戊二烯酸，丁二烯，丙烯， 1,3-丁二醇，巴豆醇或3-丁烯-1-醇。

公开(公告)号：WO2012177943A1

公开(公告)日：2012-12-27

申请号：PCT/US2012/043638

申请日：2012-06-21

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

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

IPC: C12P7/04 ,  C12N1/12

CPC classification number: C12N15/52 ,  C12N9/0008 ,  C12P7/16 ,  C12P7/18 ,  C12P7/42 ,  C12Y102/99006 ,  Y02E50/10

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

Abstract translation: 本发明提供了包含1,4-丁二醇（BDO），4-羟基丁酰辅酶A，4-羟基丁醛或腐胺途径的非天然存在的微生物，其包含至少一种编码BDO，4-羟基丁酰辅酶A， - 羟基丁醛或腐胺通路酶以足够的量表达以产生BDO，4-羟基丁酰辅酶A，4-羟基丁醛或腐胺，并进一步优化BDO的表达。 本发明另外提供了使用这些微生物生产BDO，4-羟基丁酰辅酶A，4-羟基丁醛或腐胺的方法。