公开(公告)号：US08178327B2

公开(公告)日：2012-05-15

申请号：US13009813

申请日：2011-01-19

Applicant: Mark J. Burk ,  Anthony P. Burgard ,  Robin E. Osterhout ,  Jun Sun

Inventor： Mark J. Burk ,  Anthony P. Burgard ,  Robin E. Osterhout ,  Jun Sun

IPC: C12P7/18 ,  C12N1/21

CPC classification number: C12P7/18 ,  B01D3/002 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/001 ,  C12N9/1029 ,  C12N9/1096 ,  C12N9/12 ,  C12N9/13 ,  C12N9/16 ,  C12N9/88 ,  C12N9/90 ,  C12N9/93 ,  C12N15/52 ,  C12N15/70 ,  C12N15/81 ,  C12Y101/01157 ,  C12Y402/01055

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. The invention additionally provides methods of using such microbial organisms to produce BDO.

公开(公告)号：US20120094345A1

公开(公告)日：2012-04-19

申请号：US13286135

申请日：2011-10-31

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

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

IPC: C12P7/18 ,  C12N15/63 ,  C12N1/19 ,  C12N15/53 ,  C12N1/21 ,  C12N1/15

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 organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (1,4-BDO) biosynthetic pathways. The pathways include exogenous nucleic acids encoding a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase or a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase, and e) an alcohol dehydrogenase, wherein the exogenous nucleic acids are expressed in sufficient amounts to produce 1,4-butanediol (1,4-BDO). Also provide is a method for the production of 1,4-BDO. The method includes culturing the non-naturally occurring microbial organism having 4-HB and 1,4-BDO biosynthetic pathways substantially anaerobic conditions for a sufficient period of time to produce 1,4-BDO.

Abstract translation: 本发明提供了具有4-羟基丁酸（4-HB）和1,4-丁二醇（1,4-BDO）生物合成途径的非天然存在的微生物生物。 途径包括编码a）α-酮戊二酸脱羧酶的外源核酸; b）4-羟基丁酸脱氢酶; c）4-羟基丁酰-CoA：乙酰-CoA转移酶或丁酸酯激酶和磷酸转磷酸化酶; d）醛脱氢酶，和e）醇脱氢酶，其中外源核酸以足够的量表达以产生1,4-丁二醇（1,4-BDO）。 还提供了用于生产1,4-BDO的方法。 该方法包括培养具有4-HB和1,4-BDO生物合成途径的非天然存在的微生物生物合成途径，基本上是厌氧条件足够的时间以产生1,4-BDO。

公开(公告)号：US20120094341A1

公开(公告)日：2012-04-19

申请号：US13219423

申请日：2011-08-26

Applicant: Mark J. Burk ,  Priti Pharkya ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Christophe H. Schilling

Inventor： Mark J. Burk ,  Priti Pharkya ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Christophe H. Schilling

IPC: C12P7/40 ,  C07C51/347

CPC classification number: C07C51/353 ,  C07C51/38 ,  C07C57/04 ,  C07C67/08 ,  C07C67/32 ,  C07C67/333 ,  C12P7/40 ,  C12P7/46 ,  C12P7/62 ,  Y02P20/125 ,  C07C69/60 ,  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.

Abstract translation: 本发明提供了制备丙烯酸的方法。 该方法包括在交叉复分解转化催化剂存在下使富马酸与足够量的乙烯接触，以产生约2摩尔丙烯酸/摩尔富马酸。 还提供了丙烯酸酯。 该方法包括在交叉复分解转化催化剂存在下使富马酸二酯与足够量的乙烯接触，以产生每摩尔富马酸二酯约2摩尔丙烯酸酯。 提供了用于生产丙烯酸或丙烯酸酯的方法的综合方法，其将富马酸的生物生产与易位转化相结合。 还提供丙烯酸和丙烯酸酯生产。

公开(公告)号：US08067214B2

公开(公告)日：2011-11-29

申请号：US12049256

申请日：2008-03-14

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

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

IPC: C12P7/18 ,  C12N1/21

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 organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (1,4-BDO) biosynthetic pathways. The pathways include exogenous nucleic acids encoding a) an α-ketoglutarate decarboxylase; b) a 4-hydroxybutanoate dehydrogenase; c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase or a butyrate kinase and a phosphotransbutyrylase; d) an aldehyde dehydrogenase, and e) an alcohol dehydrogenase, wherein the exogenous nucleic acids are expressed in sufficient amounts to produce 1,4-butanediol (1,4-BDO). Also provide is a method for the production of 1,4-BDO. The method includes culturing the non-naturally occurring microbial organism having 4-HB and 1,4-BDO biosynthetic pathways substantially anaerobic conditions for a sufficient period of time to produce 1,4-BDO.

Abstract translation: 本发明提供了具有4-羟基丁酸（4-HB）和1,4-丁二醇（1,4-BDO）生物合成途径的非天然存在的微生物生物。 途径包括编码a）α-酮戊二酸脱羧酶的外源核酸; b）4-羟基丁酸脱氢酶; c）4-羟基丁酰-CoA：乙酰-CoA转移酶或丁酸酯激酶和磷酸转磷酸化酶; d）醛脱氢酶，和e）醇脱氢酶，其中外源核酸以足够的量表达以产生1,4-丁二醇（1,4-BDO）。 还提供了用于生产1,4-BDO的方法。 该方法包括培养具有4-HB和1,4-BDO生物合成途径的非天然存在的微生物生物合成途径，基本上是厌氧条件足够的时间以产生1,4-BDO。

公开(公告)号：US08026386B2

公开(公告)日：2011-09-27

申请号：US12188582

申请日：2008-08-08

Applicant: Mark J. Burk ,  Priti Pharkya ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Christophe H. Schilling

Inventor： Mark J. Burk ,  Priti Pharkya ,  Stephen J. Van Dien ,  Anthony P. Burgard ,  Christophe H. Schilling

IPC: C07C67/00 ,  C07C69/52 ,  C12P7/40

CPC classification number: C07C51/353 ,  C07C51/38 ,  C07C57/04 ,  C07C67/08 ,  C07C67/32 ,  C07C67/333 ,  C12P7/40 ,  C12P7/46 ,  C12P7/62 ,  Y02P20/125 ,  C07C69/60 ,  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.

Abstract translation: 本发明提供了制备丙烯酸的方法。 该方法包括在交叉复分解转化催化剂存在下使富马酸与足够量的乙烯接触，以产生约2摩尔丙烯酸/摩尔富马酸。 还提供了丙烯酸酯。 该方法包括在交叉复分解转化催化剂存在下使富马酸二酯与足够量的乙烯接触，以产生每摩尔富马酸二酯约2摩尔丙烯酸酯。 提供了用于生产丙烯酸或丙烯酸酯的方法的综合方法，其将富马酸的生物生产与易位转化相结合。 还提供丙烯酸和丙烯酸酯生产。

公开(公告)号：US20110223637A1

公开(公告)日：2011-09-15

申请号：US13106764

申请日：2011-05-12

Applicant: Mark J. Burk ,  Christophe H. Schilling ,  Anthony P. Burgard ,  John D. Trawick

Inventor： Mark J. Burk ,  Christophe H. Schilling ,  Anthony P. Burgard ,  John D. Trawick

IPC: C12P19/40 ,  C12N1/00

CPC classification number: C12P7/18 ,  C12N9/0008 ,  C12N9/0036 ,  C12N9/1007 ,  C12N9/93 ,  C12N15/70 ,  C12P19/32 ,  Y02E50/343

Abstract: The invention provides a non-naturally occurring microbial organism having an acetyl-CoA pathway and the capability of utilizing syngas or syngas and methanol. In one embodiment, the invention provides a non-naturally occurring microorganism, comprising one or more exogenous proteins conferring to the microorganism a pathway to convert CO, CO2 and/or H2 to acetyl-coenzyme A (acetyl-CoA), methyl tetrahydrofolate (methyl-THF) or other desired products, wherein the microorganism lacks the ability to convert CO or CO2 and H2 to acetyl-CoA or methyl-THF in the absence of the one or more exogenous proteins. For example, the microbial organism can contain at least one exogenous nucleic acid encoding an enzyme or protein in an acetyl-CoA pathway. The microbial organism is capable of utilizing synthesis gases comprising CO, CO2 and/or H2, alone or in combination with methanol, to produce acetyl-CoA. The invention additionally provides a method for producing acetyl-CoA, for example, by culturing an acetyl-CoA producing microbial organism, where the microbial organism expresses at least one exogenous nucleic acid encoding an acetyl-CoA pathway enzyme or protein in a sufficient amount to produce acetyl-CoA, under conditions and for a sufficient period of time to produce acetyl-CoA.

Abstract translation: 本发明提供具有乙酰-CoA途径的非天然存在的微生物生物体，以及利用合成气或合成气和甲醇的能力。 在一个实施方案中，本发明提供非天然存在的微生物，其包含一种或多种外源蛋白质，赋予微生物将CO，CO 2和/或H 2转化为乙酰辅酶A（乙酰辅酶A），甲基四氢叶酸（甲基 -THF）或其它所需产物，其中微生物缺乏在不存在一种或多种外源蛋白的情况下将CO或CO 2和H 2转化为乙酰辅酶A或甲基-THF的能力。 例如，微生物生物体可以含有至少一种编码乙酰辅酶A途径中的酶或蛋白质的外源核酸。 微生物生物能够单独或与甲醇组合使用包含CO，CO 2和/或H 2的合成气体，以产生乙酰辅酶A。 本发明另外提供了生产乙酰辅酶A的方法，例如通过培养产生乙酰辅酶A的微生物，其中微生物生物体表达至少一种编码乙酰辅酶A途径酶或蛋白质的外源核酸，其量足够 在条件下和足够的时间内产生乙酰辅酶A产生乙酰辅酶A。

公开(公告)号：US07977084B2

公开(公告)日：2011-07-12

申请号：US12398996

申请日：2009-03-05

Applicant: Jun Sun ,  Priti Pharkya ,  Anthony P. Burgard

Inventor： Jun Sun ,  Priti Pharkya ,  Anthony P. Burgard

IPC: C12N1/00 ,  C12P7/16 ,  C12P7/04

CPC classification number: C12P7/04 ,  C12N9/0006 ,  C12N9/0008 ,  C12N9/001 ,  C12N9/1029 ,  C12N9/88 ,  C12N15/52 ,  C12P7/02 ,  C12Y101/01001 ,  C12Y101/01035 ,  C12Y102/0105 ,  C12Y203/01009 ,  C12Y203/01016 ,  C12Y402/01017

Abstract: The invention provides a non-naturally occurring microbial organism having at least one exogenous gene insertion and/or one or more gene disruptions that confer production of primary alcohols. A method for producing long chain alcohols includes culturing these non-naturally occurring microbial organisms.

Abstract translation: 本发明提供了具有至少一种外源基因插入和/或一种或多种赋予伯醇生产的基因破坏的非天然存在的微生物生物。 制备长链醇的方法包括培养这些非天然存在的微生物。

公开(公告)号：US20100330635A1

公开(公告)日：2010-12-30

申请号：US12772114

申请日：2010-04-30

Applicant: Anthony P. Burgard ,  Mark J. Burk ,  Robin E. Osterhout ,  Priti Pharkya

Inventor： Anthony P. Burgard ,  Mark J. Burk ,  Robin E. Osterhout ,  Priti Pharkya

IPC: C12P7/18 ,  C12N1/00

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生物体包括具有1,3-丁二醇（1,3-BDO）途径的微生物生物，其具有至少一种编码1,3-BDO途径酶的外源核酸，所述外源核酸以足够的量表达，以产生1 ，3-BDO。 该途径包括选自2-氨基-4-酮戊酸酯（AKP）硫解酶，AKP脱氢酶，2-氨基-4-羟基戊酸转氨酶，2-氨基-4-羟基戊酸酯氧化还原酶（脱氨基），2- 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），2,4-二氧代戊酸脱羧酶，3-氧代丁醛还原酶（还原酮），3-氧代丁醛还原酶 ），4-羟基-2-丁酮还原酶，AKP脱羧酶，4-氨基丁-2-酮氨基转移酶，4-氨基丁-2-酮氧化还原酶（脱氨基），4-氨基丁-2-酮氨裂解酶 乙酰乙酰辅酶A还原酶（CoA依赖性醛形成），乙酰乙酰辅酶A还原酶（CoA依赖性醇形成），乙酰乙酰辅酶A还原酶（酮），乙酰乙酰辅酶A还原酶 还原），3-羟基丁酰辅酶A还原酶（醛形成），3-羟基 Ryl-CoA还原酶（醇形成），4-羟基丁酰辅酶A脱水酶和巴豆酸酶。 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生产1,3-BDO。

公开(公告)号：US20090275096A1

公开(公告)日：2009-11-05

申请号：US12433829

申请日：2009-04-30

Applicant: Anthony P. Burgard ,  Mark J. Burk ,  Robin E. Osterhout ,  Priti Pharkya

Inventor： Anthony P. Burgard ,  Mark J. Burk ,  Robin E. Osterhout ,  Priti Pharkya

IPC: C12P7/52 ,  C12N1/00 ,  C12P7/40

CPC classification number: C12P7/42 ,  C12N9/0008 ,  C12N9/1096 ,  C12N9/88 ,  C12N9/90 ,  C12P7/40 ,  C12Y102/01 ,  C12Y206/01022 ,  C12Y403/01 ,  C12Y504/99002

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.

Abstract translation: 本发明提供了具有2-羟基异丁酸，3-羟基异丁酸或甲基丙烯酸途径的非天然存在的微生物生物。 微生物生物体含有编码2-羟基异丁酸，3-羟基异丁酸或甲基丙烯酸途径中的酶的至少一种外源核酸。 本发明还提供了2-羟基异丁酸，3-羟基异丁酸或甲基丙烯酸的制备方法。 该方法可以包括培养足够量的表达至少一种编码2-羟基异丁酸，3-羟基异丁酸或甲基丙烯酸途径酶的外源核酸的2-羟基异丁酸，3-羟基异丁酸或产生甲基丙烯酸的微生物，并培养 在条件下和足够的时间内产生2-羟基异丁酸，3-羟基异丁酸或甲基丙烯酸。

公开(公告)号：US12264354B2

公开(公告)日：2025-04-01

申请号：US15488320

申请日：2017-04-14

Applicant: Genomatica, Inc.

Inventor： Anthony P. Burgard ,  Robin E. Osterhout ,  Stephen J. Van Dien ,  Cara Ann Tracewell ,  Priti Pharkya ,  Stefan Andrae

IPC: C12P7/18 ,  C07D207/12 ,  C08G18/32 ,  C08G63/06 ,  C08G63/12 ,  C08G63/66 ,  C08G69/26 ,  C12N9/04 ,  C12N9/06 ,  C12N9/10 ,  C12N9/88 ,  C12P7/24 ,  C12P19/02

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 1,4-butanediol (BDO). Also provided herein are methods for using such an organism to produce BDO.