公开(公告)号：WO2010071697A1

公开(公告)日：2010-06-24

申请号：PCT/US2009/050757

申请日：2009-07-15

Applicant: GENOMATICA, INC. ,  TRAWICK, John, D. ,  BURK, Mark, J. ,  BURGARD, Anthony, P.

Inventor： TRAWICK, John, D. ,  BURK, Mark, J. ,  BURGARD, Anthony, P.

IPC: C12N1/00 ,  C12N1/21 ,  C12P5/00

CPC classification number: C12P7/18 ,  C12N9/0006 ,  C12N9/10 ,  C12N9/1029 ,  C12N9/88 ,  C12N15/52 ,  C12P7/04 ,  C12P7/42

Abstract: An exemplary non-naturally occurring microbial organism having an isopropanol pathway includes at least one exogenous nucleic acid encoding an isopropanol pathway enzyme expressed in a sufficient amount to produce isopropanol and includes a succinyl-CoA:3-ketoacid-CoA transferase. Another organism having a 4-hydroxybutryate pathway includes at least one exogenous nucleic acid including an acetoacetyl-CoA thiolase, a 3-hydroxybutyryl-CoA dehydrogenase, a crotonase, a crotonyl-CoA hydratase, a 4-hydroxybutyryl-CoA transferase, a phosphotrans-4-hydroxybutyrylase, and a 4-hydroxybutyrate kinase. An exemplary organism having a 1,4-butanediol pathway includes an acetoacetyl-CoA thiolase, a 3-Hydroxybutyryl-CoA dehydrogenase, a crotonase, a crotonyl-CoA hydratase, a 4-hydroxybutyryl-CoA reductase (alcohol forming), a 4-hydroxybutyryl-CoA reductase (aldehyde forming), and a 1,4-butanediol dehydrogenase. Such an organism further comprising an acetyl-CoA pathway. Any of the aforementioned organisms are cultured to produce isopropanol, 4-hydroxybutryate, or 1,4- butanediol.

Abstract translation: 具有异丙醇途径的示例性非天然存在的微生物生物体包括至少一种编码异丙醇途径酶的外源核酸，其以足以产生异丙醇的量表达，并且包括琥珀酰-CoA：3-酮酸 - 辅酶A转移酶。 具有4-羟基丁酸酯途径的另一种生物体包括至少一种外源核酸，包括乙酰乙酰辅酶A硫解酶，3-羟基丁酰辅酶A脱氢酶，巴豆酸酶，巴豆酰辅酶A水合酶，4-羟基丁酰辅酶A转移酶， 4-羟基丁酸酯酶和4-羟基丁酸酯激酶。 具有1,4-丁二醇途径的示例性生物体包括乙酰乙酰辅酶A硫解酶，3-羟基丁酰辅酶A脱氢酶，巴豆酸酶，巴豆酰辅酶A水合酶，4-羟基丁酰辅酶A还原酶（醇形成），4- 羟基丁酰辅酶A还原酶（醛形成）和1,4-丁二醇脱氢酶。 这种生物体还包含乙酰辅酶A途径。 任何上述生物被培养以产生异丙醇，4-羟基丁酸酯或1,4-丁二醇。

公开(公告)号：WO2009135074A3

公开(公告)日：2009-11-05

申请号：PCT/US2009/042426

申请日：2009-04-30

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: C12P7/42 ,  C12N1/20

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

公开(公告)号：WO2009023493A1

公开(公告)日：2009-02-19

申请号：PCT/US2008/072362

申请日：2008-08-06

Applicant: GENOMATICA, INC. ,  BURGARD, Anthony, P. ,  VAN DIEN, Stephen, J. ,  BURK, Mark, J.

Inventor： BURGARD, Anthony, P. ,  VAN DIEN, Stephen, J. ,  BURK, Mark, J.

IPC: C12N15/52 ,  C12P7/18 ,  C12N1/00

CPC classification number: C12P7/18 ,  B01D3/002 ,  C12N9/0006

Abstract: The invention provides a non- naturally occurring microorganism comprising one or more gene disruptions, the one or more gene disruptions occurring in genes encoding an enzyme obligatory to coupling 1,4-butanediol production to growth of the microorganism when the gene disruption reduces an activity of the enzyme, whereby theone or more gene disruptions confers stable growth-coupled production of 1,4-butanediol onto the non- naturally occurring microorganism. The microorganism can further comprise a gene encoding an enzyme in a 1,4- butanediol (BDO) biosynthetic pathway. The invention additionally relates to methods of using microorganisms to produce BDO.

Abstract translation: 本发明提供了一种非天然存在的微生物，其包含一种或多种基因破坏，所述一个或多个基因破坏发生在编码需要将1,4-丁二醇产生与微生物生长偶联的酶的基因中，当基因破坏降低活性时 所述酶，其中所述一种或多种基因破坏赋予所述非天然存在的微生物上1,4-丁二醇稳定的生长偶联产生。 微生物还可以包含编码1,4-丁二醇（BDO）生物合成途径中的酶的基因。 本发明还涉及使用微生物来生产BDO的方法。

公开(公告)号：WO2014004625A1

公开(公告)日：2014-01-03

申请号：PCT/US2013/047821

申请日：2013-06-26

Applicant: GENOMATICA, INC.

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

IPC: C12N1/21 ,  C12N15/53 ,  C12N15/54 ,  C12P7/04

CPC classification number: C12N15/52 ,  C12P7/18

Abstract: The invention provides a non-naturally occurring microbial organism containing an ethylene glycol pathway, wherein the pathway includes at least one exogenous nucleic acid encoding an ethylene glycol pathway enzyme expressed in a sufficient amount to produce ethylene glycol. The non-naturally occurring microorganisms of the invention can express exogenous nucleic acids that catalyze the fixation of C02 or CO to ethylene glycol. The microorganisms of the invention can further include enzymes to generate energy and reducing equivalents from methanol, syngas and other gaseous sources. The invention additionally provides methods of using such microbial organisms to produce ethylene glycol, by culturing a non-naturally occurring microbial organism containing an ethylene glycol pathway under conditions and for a sufficient period of time to produce ethylene glycol.

Abstract translation: 本发明提供了含有乙二醇途径的非天然存在的微生物生物，其中该途径包括至少一种编码乙醇途径酶的外源核酸，其以足够的量表达以产生乙二醇。 本发明的非天然存在的微生物可以表达催化将CO 2或CO固定于乙二醇的外源核酸。 本发明的微生物可进一步包括产生能量和减少甲醇，合成气和其它气体源的当量的酶。 本发明还提供使用这种微生物生产乙二醇的方法，通过在条件和足够的时间内培养含有乙二醇途径的非天然存在的微生物生物来生产乙二醇。

公开(公告)号：WO2013040383A1

公开(公告)日：2013-03-21

申请号：PCT/US2012/055469

申请日：2012-09-14

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

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

IPC: C12N15/74

CPC classification number: C12P5/026 ,  C12N9/1205 ,  C12N9/1229 ,  C12N9/1235 ,  C12N9/88 ,  C12N15/52 ,  C12P5/002 ,  C12Y402/03

Abstract: Non-naturally occurring microbial organisms are disclosed containing an alkene pathway having at least one exogenous nucleic acid encoding an alkene pathway enzyme expressed in a sufficient amount to convert an alcohol to an alkene. The disclosure additionally provides methods of using such microbial organisms to produce an alkene, by culturing a non-naturally occurring microbial organism containing an alkene pathway as described herein under conditions and for a sufficient period of time to produce an alkene.

Abstract translation: 公开了非天然存在的微生物，其含有具有至少一种编码烯烃途径酶的外源核酸的烯烃途径，所述烯酸途径酶以足够的量转化成烯烃的醇。 本公开另外提供了使用这种微生物生产烯烃的方法，通过在条件和足够的时间段内培养含有如本文所述的烯烃途径的非天然存在的微生物生物产生烯烃。

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：WO2010057022A1

公开(公告)日：2010-05-20

申请号：PCT/US2009/064433

申请日：2009-11-13

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

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

IPC: C12P7/26 ,  C12P7/00 ,  C12N1/21

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

Abstract: A non-naturally occurring microbial organism having a methyl ethyl ketone pathway includes at least one exogenous nucleic acid encoding a methyl ethyl ketone pathway enzyme expressed in a sufficient amount to produce methyl ethyl ketone. The methyl ethyl ketone pathway includes a β-ketothiolase, a β-ketovalerate decarboxylase and an enzyme selected from the group consisting of a β-ketovaleryl-CoA hydrolase and a β-ketovaleryl-CoA transferase. Alternatively, the methyl ethyl ketone pathway includes a 2-methylacetoacetyl-CoA thiolase, a 2-methylacetoacetate decarboxylase and an enzyme selected from the group consisting of a 2-methylacetoacetyl-CoA hydrolase and a 2-methylacetoacetyl-CoA transferase. Either pathway can further include a methyl ethyl ketone reductase to produce 2-BuOH. A method for producing methyl ethyl ketone or 2-BuOH includes culturing these non-naturally occurring microbial organisms under conditions, and for a sufficient period of time, to produce methyl ethyl ketone or 2-BuOH.

Abstract translation: 具有甲基乙基酮途径的非天然存在的微生物包括至少一种编码甲基乙基酮途径酶的外源核酸，其以足以产生甲基乙基酮的量表达。 甲基乙基酮途径包括β-酮硫解酶，β-酮戊二酸脱羧酶和选自β-酮戊酰基-CoA水解酶和β-酮戊酰基-CoA转移酶的酶。 或者，甲基乙基酮途径包括2-甲基乙酰乙酰辅酶A硫解酶，2-甲基乙酰乙酸脱羧酶和选自2-甲基乙酰乙酰辅酶A水解酶和2-甲基乙酰乙酰辅酶A转移酶的酶。 任一途径还可以包括甲基乙基酮还原酶以产生2-BuOH。 一种生产甲基乙基酮或2-BuOH的方法包括在条件和足够的时间内培养这些非天然存在的微生物生产甲基乙基酮或2-BuOH。

公开(公告)号：WO2009045637A9

公开(公告)日：2009-04-09

申请号：PCT/US2008/072679

申请日：2008-08-08

Applicant: GENOMATICA, INC. ,  BURK, Mark, J. ,  PHARKYA, Priti ,  VAN DIEN, Stephen, J. ,  BURGARD, Anthony, P. ,  SCHILLING, Christopher, H.

Inventor： BURK, Mark, J. ,  PHARKYA, Priti ,  VAN DIEN, Stephen, J. ,  BURGARD, Anthony, P. ,  SCHILLING, Christopher, H.

IPC: C07C51/347 ,  C07C67/333 ,  C12P7/46 ,  C07C57/04 ,  C07C69/54

Abstract: The invention provides a method of producing acrylic acid. The method includes contacting fumaric acid with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylic acid per mole of fumaric acid. Also provided is an acrylate ester. The method includes contacting fumarate diester with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylate ester per mole of fumarate diester. An integrated process for process for producing acrylic acid or acrylate ester is provided which couples bioproduction of fumaric acid with metathesis transformation. An acrylic acid and an acrylate ester production also is provided.

公开(公告)号：WO2009045637A3

公开(公告)日：2009-04-09

申请号：PCT/US2008/072679

申请日：2008-08-08

Applicant: GENOMATICA, INC. ,  BURK, Mark, J. ,  PHARKYA, Priti ,  VAN DIEN, Stephen, J. ,  BURGARD, Anthony, P. ,  SCHILLING, Christopher, H.

Inventor： BURK, Mark, J. ,  PHARKYA, Priti ,  VAN DIEN, Stephen, J. ,  BURGARD, Anthony, P. ,  SCHILLING, Christopher, H.

IPC: C07C51/347 ,  C07C67/333 ,  C12P7/46 ,  C07C57/04 ,  C07C69/54

Abstract: The invention provides a method of producing acrylic acid. The method includes contacting fumaric acid with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylic acid per mole of fumaric acid. Also provided is an acrylate ester. The method includes contacting fumarate diester with a sufficient amount of ethylene in the presence of a cross-metathesis transformation catalyst to produce about two moles of acrylate ester per mole of fumarate diester. An integrated process for process for producing acrylic acid or acrylate ester is provided which couples bioproduction of fumaric acid with metathesis transformation. An acrylic acid and an acrylate ester production also is provided.

公开(公告)号：WO2014190251A1

公开(公告)日：2014-11-27

申请号：PCT/US2014/039322

申请日：2014-05-23

Applicant: GENOMATICA, INC.

Inventor： ADELSTEIN, Benjamin ,  OSTERHOUT, Robin, E. ,  BURK, Mark, J.

IPC: C12P1/04

CPC classification number: C12P7/62 ,  A23L33/135 ,  A23V2002/00 ,  A61K31/22 ,  A61K35/66 ,  A61K36/064 ,  C07B2200/05 ,  C07C69/675 ,  C12N9/18 ,  C12N15/52 ,  C12P7/42 ,  C12R1/01 ,  C12R1/645 ,  C12Y101/01035 ,  C12Y101/011 ,  C12Y301/01067 ,  C12Y301/08001 ,  Y02P20/127

Abstract: Provided herein are non-naturally occurring microbial organisms having a pathway for production of (3R)-hydroxybutyl (3R)-hydroxybutyrate, wherein the organism can further include a (R)-l,3-butanediol pathway, a (3R)-hydroxybutyrate pathway, a (3R)- hydroxybutyryl-CoA pathway, an acetoacetate pathway, an acetoacetyl-CoA pathway, a (3R)-hydroxybutyl-ACP pathway, or an acetoacetyl-ACP pathway. Additionally provided are methods and processes for producing and isolating (3R)-hydroxybutyl (3R)- hydroxybutyrate using the microbial organisms, and various compositions having the (3R)-hydroxybutyl (3R)-hydroxybutyrate. Still further provided are methods of treating or preventing a disease, disorder or condition using the (3R)-hydroxybutyl (3R)-hydroxybutyrate produced by the microbial organisms of the invention.

Abstract translation: 本文提供了具有生产（3R） - （3R） - 羟基丁酸酯途径的非天然存在的微生物生物，其中生物体还可包含（R）-1,3-丁二醇途径，（3R） - 羟基丁酸酯 途径，（3R） - 羟基丁酰辅酶A途径，乙酰乙酸途径，乙酰乙酰辅酶A途径，（3R） - 羟基丁基ACP途径或乙酰乙酰-ACP途径。 另外提供了使用微生物生物体和（3R） - 羟基丁基（3R） - 羟基丁酸酯生产和分离（3R） - （3R） - 羟基丁酸的羟基丁酸的方法和方法。 还提供了使用本发明的微生物生物体产生的（3R） - 羟基丁酸（3R） - 羟基丁酸酯来治疗或预防疾病，病症或病症的方法。