公开(公告)号：EP2821494B1

公开(公告)日：2017-03-08

申请号：EP14178905.7

申请日：2008-03-14

Applicant: Genomatica, Inc.

Inventor： Burk, Mark J. ,  Van Dien, Stephen J. ,  Burgard, Anthony ,  Niu, Wei

IPC: C12P1/00 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12N9/00 ,  C12N9/02 ,  C12N9/04 ,  C12N9/88

CPC classification number: C12N15/52 ,  B01D3/002 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/88 ,  C12N9/93 ,  C12N15/70 ,  C12N15/81 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12Y101/01061 ,  C12Y102/01076 ,  C12Y401/01071 ,  C12Y602/01004 ,  Y02P20/52

Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or ±-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or ±-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric 4-hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, ±-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.

Abstract translation: 本发明提供一种非天然存在的微生物的生物催化剂包括具有4-羟基丁酸（4-HB），其具有至少一种外源性核酸编码4-羟基丁酸脱氢酶，琥珀酰辅酶A合成酶，CoA-依赖性琥珀半醛生物合成途径的微生物 脱氢酶，或α-酮戊二酸±脱羧酶，worin所述外源核酸被足量的过表达以产生单体4-羟基丁酸（4-HB）。 所以提供一种非天然存在的微生物的生物催化剂包括具有4-羟基丁酸（4-HB）和1,4-丁二醇（BDO）的生物合成途径的微生物，所述途径包括至少一种外源性核酸编码4-羟基丁酸脱氢酶 ，琥珀酰辅酶A合成酶，CoA-依赖性琥珀酸半醛脱氢酶，4-羟基丁酸：CoA转移酶，4-丁酸激酶，phosphotransbutyrylase，±α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶，worin所述外源核酸是 表示以足够的量，以产生1,4-丁二醇（BDO）。 另外提供了一种用于生产4- HB的方法。 该方法包括培养具有4-羟基丁酸（4-HB）生物合成途径包含至少一种外源核酸编码4-羟基丁酸脱氢酶，琥珀酰辅酶A合成酶，CoA-依赖性琥珀酸半醛脱氢酶或±非天然存在的微生物 基本上厌氧的条件下α-酮戊二酸脱羧酶的一段足够的时间以产生单体4-羟基丁酸（4-HB）。 进一步提供的是用于生产BDO的方法。 该方法包括培养的非天然存在的微生物的生物催化剂，其包含具有4-羟基丁酸（4-HB）和1,4-丁二醇（BDO）的生物合成途径的微生物，所述的途径包括至少一种外源性核酸编码4- 羟基丁酸酯脱氢酶，琥珀酰辅酶A合成酶，CoA-依赖性琥珀酸半醛脱氢酶，4-羟基丁酸：CoA转移酶，4-羟基丁酸酯激酶，phosphotranshydroxybutyrylase，±α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶的一段足够的 时间，以产生1,4-丁二醇（BDO）。 的4-HB和/或BDO产品可被分泌到培养基中。

公开(公告)号：EP4407037A3

公开(公告)日：2024-10-09

申请号：EP23210974.4

申请日：2014-12-23

Applicant: Genomatica, Inc.

Inventor： Burgard, Anthony P. ,  Osterhout, Robin E. ,  Van Dien, Stephen J. ,  Pharkya, Priti ,  Yang, Tae Hoon ,  Choi, Jungik

IPC: C12N1/21 ,  C12P7/52 ,  C12P1/04 ,  C12P7/16

CPC classification number: C07K14/245 ,  C12N1/20 ,  C12N9/0036 ,  C12N9/0057 ,  C12N9/1205 ,  C12N9/16 ,  C12N9/93 ,  C12N15/52 ,  C12P7/42 ,  C12P7/18 ,  C12N9/52 ,  C12N9/88 ,  C12Y106/01002 ,  C12Y110/03 ,  C12Y207/0104 ,  C12Y301/00 ,  C12Y301/02 ,  C12Y301/02002 ,  C12Y304/21092 ,  C12Y401/01031 ,  C12Y401/01032 ,  Y02E50/10

Abstract: The invention is directed to a non-naturally occurring microbial organism comprising a first attenuation of a succinyl-CoA synthetase or transferase and at least a second attenuation of a succinyl-CoA converting enzyme or a gene encoding a succinate producing enzyme within a multi-step pathway having a net conversion of succinyl-CoA to succinate.

公开(公告)号：EP3392340A1

公开(公告)日：2018-10-24

申请号：EP18162505.4

申请日：2010-06-04

Applicant: Genomatica, Inc.

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: C12P7/16

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-utanediol (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.

公开(公告)号：EP3831951A2

公开(公告)日：2021-06-09

申请号：EP20170580.3

申请日：2013-06-03

Applicant: Genomatica, Inc.

Inventor： Burk, Mark J. ,  Pharkya, Priti ,  Burgard, Anthony P. ,  Van Dien, Stephen J. ,  Osterhout, Robin E. ,  Trawick, John D. ,  Kuchinskas, Michael P. ,  Steer, Brian

IPC: C12P7/52 ,  C12N1/20 ,  C12N1/21

Abstract: The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate, 1,4-butanediol, or other product pathway and being capable of producing 4-hydroxybutyrate, 1,4-butandiol, or other product, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyrate, 1,4-butanediol, or other product or related products using the microbial organisms.

公开(公告)号：EP3214179A1

公开(公告)日：2017-09-06

申请号：EP17151965.5

申请日：2008-03-14

Applicant: Genomatica, Inc.

Inventor： Burk, Mark J. ,  Van Dien, Stephen J. ,  Burgard, Anthony P. ,  Niu, Wei

IPC: C12P1/00 ,  C12N9/88 ,  C12N9/00 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12N15/52

CPC classification number: C12N15/52 ,  B01D3/002 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/88 ,  C12N9/93 ,  C12N15/70 ,  C12N15/81 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12Y101/01061 ,  C12Y102/01076 ,  C12Y401/01071 ,  C12Y602/01004 ,  Y02P20/52

Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or α-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or α-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric 4-hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.

Abstract translation: 本发明提供一种非天然存在的微生物生物催化剂，其包括具有4-羟基丁酸（4-HB）生物合成途径的微生物生物体，所述生物合成途径具有至少一种编码4-羟基丁酸脱氢酶，琥珀酰-CoA合成酶，CoA-依赖性琥珀酸半醛的外源核酸 脱氢酶或α-酮戊二酸脱羧酶，其中所述外源核酸以足够量表达以产生单体4-羟基丁酸（4-HB）。 还提供了包含具有4-羟基丁酸（4-HB）和1,4-丁二醇（BDO）生物合成途径的微生物的非天然存在的微生物生物催化剂，所述途径包括至少一种编码4-羟基丁酸脱氢酶 ，琥珀酰-CoA合成酶，辅酶A依赖性琥珀酸半醛脱氢酶，4-羟基丁酸：CoA转移酶，4-丁酸激酶，磷酸转丁酰酶，α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶，其中外源核酸是 以足够的量表达以产生1,4-丁二醇（BDO）。 另外提供了用于生产4-HB的方法。 该方法包括培养具有4-羟基丁酸（4-HB）生物合成途径的非天然存在的微生物，所述生物合成途径包括至少一种编码4-羟基丁酸脱氢酶，琥珀酰-CoA合成酶，CoA-依赖性琥珀酸半醛脱氢酶或α α-酮戊二酸脱羧酶在基本上厌氧的条件下反应足够的时间以产生单体4-羟基丁酸（4-HB）。 还提供了一种生产BDO的方法。 该方法包括培养包含具有4-羟基丁酸（4-HB）和1,4-丁二醇（BDO）生物合成途径的微生物的非天然存在的微生物生物催化剂，所述途径包括至少一种编码4-羟基丁酸 琥珀酰-CoA合成酶，辅酶A依赖性琥珀酸半醛脱氢酶，4-羟基丁酸酯：辅酶A转移酶，4-羟基丁酸酯激酶，磷酸转羟基丁酰酶，α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶处理足够的时间 一次生产1,4-丁二醇（BDO）。 4-HB和/或BDO产物可以分泌到培养基中。

公开(公告)号：EP2821494A1

公开(公告)日：2015-01-07

申请号：EP14178905.7

申请日：2008-03-14

Applicant: Genomatica, Inc.

Inventor： Burk, Mark J. ,  Van Dien, Stephen J. ,  Burgard, Anthony ,  Niu, Wei

IPC: C12P1/00 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12N9/00 ,  C12N9/02 ,  C12N9/04 ,  C12N9/88

CPC classification number: C12N15/52 ,  B01D3/002 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/88 ,  C12N9/93 ,  C12N15/70 ,  C12N15/81 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12Y101/01061 ,  C12Y102/01076 ,  C12Y401/01071 ,  C12Y602/01004 ,  Y02P20/52

Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or α-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or α-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric 4-hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.

公开(公告)号：EP3800262A1

公开(公告)日：2021-04-07

申请号：EP20192882.7

申请日：2008-03-14

Applicant: Genomatica, Inc.

Inventor： Burk, Mark J. ,  Van Dien, Stephen J. ,  Burgard, Anthony P. ,  Niu, Wei

IPC: C12P1/00 ,  C12P7/18 ,  C12P7/42 ,  C12P7/52 ,  C12P17/04 ,  C12N9/00 ,  C12N9/02 ,  C12N9/04 ,  C12N9/88

Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or α-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided is a method for the production of 4-HB. The method includes culturing a non-naturally occurring microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase or α-ketoglutarate decarboxylase under substantially anaerobic conditions for a sufficient period of time to produce monomeric 4-hydroxybutanoic acid (4-HB). Further provided is a method for the production of BDO. The method includes culturing a non-naturally occurring microbial biocatalyst, comprising a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways including at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-hydroxybutyrate kinase, phosphotranshydroxybutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase for a sufficient period of time to produce 1,4-butanediol (BDO). The 4-HB and/or BDO products can be secreted into the culture medium.

公开(公告)号：EP2679685A1

公开(公告)日：2014-01-01

申请号：EP13001196.8

申请日：2008-08-06

Applicant: Genomatica, Inc.

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.

公开(公告)号：EP2679684A1

公开(公告)日：2014-01-01

申请号：EP13001195.0

申请日：2008-08-06

Applicant: Genomatica, Inc.

Inventor： Burgard, Anthony P. ,  Van Dien, Stephen J. ,  Burk, Mark J.

IPC: C12N15/52 ,  C12P7/18 ,  C12N1/00 ,  C12N9/04

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: 本发明提供包含一种或多种基因破坏的非天然存在的微生物，所述一种或多种基因破坏发生在编码当1,4-丁二醇产生与微生物的生长偶联以使基因破坏降低 所述酶，其中所述一种或多种基因破坏赋予1,4-丁二醇在非天然存在的微生物上的稳定生长偶联产生。 微生物可以进一步包含编码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生产BDO的方法。

公开(公告)号：EP2679676A1

公开(公告)日：2014-01-01

申请号：EP13001197.6

申请日：2008-08-06

Applicant: Genomatica, Inc.

Inventor： Burgard, Anthony P. ,  Van Dien, Stephen J. ,  Burk, Mark J.

IPC: C12N9/04 ,  C12P7/18

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 microorganism to produce BDO.

Abstract translation: 本发明提供包含一种或多种基因破坏的非天然存在的微生物，所述一种或多种基因破坏发生在编码当1,4-丁二醇产生与微生物的生长偶联以使基因破坏降低 所述酶，其中所述一种或多种基因破坏赋予1,4-丁二醇在非天然存在的微生物上的稳定生长偶联产生。 微生物可以进一步包含编码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生产BDO的方法。