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：WO2014071286A1

公开(公告)日：2014-05-08

申请号：PCT/US2013/068254

申请日：2013-11-04

Applicant: GENOMATICA, INC.

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

IPC: C07C31/22 ,  C12P7/20

CPC classification number: C12P7/24 ,  C12N1/14 ,  C12N1/16 ,  C12N1/20 ,  C12N9/0006 ,  C12N9/0028 ,  C12N9/1007 ,  C12N15/52 ,  C12P7/04 ,  C12P7/18 ,  C12P7/20 ,  C12Y101/01244 ,  C12Y105/0102

Abstract: Provided herein is a non-naturally occurring microbial organism (NNOMO) having a methanol metabolic pathway (MMP) 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 1,2-propanediol (1,2-PDO), n- propanol (n-PrOH), 1,3-propanediol (1,3-PDO) or glycerol. Also provided herein are methods for using such an organism to produce 1,2-PDO, n-PrOH, 1,3-PDO or glycerol.

Abstract translation: 本文提供了具有甲醇代谢途径（MMP）的非天然存在的微生物生物体（NNOMO），其可以在甲醇存在下增强还原当量的可用性。 这种还原当量可用于提高由微生物生产的有机化合物的产物产率，例如1,2-丙二醇（1,2-PDO），正丙醇（n-PrOH），1,3-丙二醇（ 1,3-PDO）或甘油。 本文还提供了使用这种生物体产生1,2-PDO，n-PrOH，1,3-PDO或甘油的方法。

公开(公告)号：WO2012177726A1

公开(公告)日：2012-12-27

申请号：PCT/US2012/043293

申请日：2012-06-20

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: C12P5/02 ,  C12N15/74 ,  C12N1/00

CPC classification number: C12P7/04 ,  C12N15/52 ,  C12P7/24 ,  C12P7/6409 ,  C12P7/6436

Abstract: The invention provides a non-naturally occurring microbial organism having a microbial organism having at least one exogenous gene insertion and/or one or more gene disruptions that confer production of primary alcohols and at least one exogenous nucleic acid that encodes an enzyme that increases the yields of the primary alcohol by (i) enhancing carbon fixation via the reductive TCA cycle, and/or (ii) accessing additional reducing equivalents from gaseous carbon sources and/or syngas components such as CO, C02, and/or H2. 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/或一种或多种基因破坏的非天然存在的微生物生物体，所述基因破坏产生伯醇和至少一种编码增加产量的酶的外源核酸 通过（i）通过还原TCA循环增强碳固定，和/或（ii）从气态碳源和/或合成气组分如CO，CO 2和/或H 2获得另外的还原当量。 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：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：WO2011047101A1

公开(公告)日：2011-04-21

申请号：PCT/US2010/052570

申请日：2010-10-13

Applicant: GENOMATICA, INC. ,  HASELBECK, Robert ,  TRAWICK, John, D. ,  NIU, Wei ,  BURGARD, Anthony, P.

Inventor： HASELBECK, Robert ,  TRAWICK, John, D. ,  NIU, Wei ,  BURGARD, Anthony, P.

IPC: C12P7/26 ,  C12N1/20

CPC classification number: C12P7/18 ,  C12P7/24 ,  C12P7/42 ,  C12P13/001 ,  C12P19/40

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, A- 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， - 羟基丁醛或腐胺途径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种微生物生物制备BDO，4-羟基丁酰辅酶A，4-羟基丁醛或腐胺的方法。

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：WO2015077752A1

公开(公告)日：2015-05-28

申请号：PCT/US2014/067282

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: C12N15/52 ,  C12N9/0006 ,  C12N9/1022 ,  C12N9/88 ,  C12N9/90 ,  C12P7/04 ,  C12Y101/01244 ,  C12Y202/01003 ,  C12Y401/02043 ,  C12Y503/01027

Abstract: The invention provides non-naturally occurring microbial organisms having a formaldehyde fixation pathway, a formate assimilation pathway, and/or a methanol metabolic pathway in combination with a fatty alcohol, fatty aldehyde, fatty acid or isopropanol pathway, wherein the microbial organisms selectively produce a fatty alcohol, fatty aldehyde or fatty acid of a specified length or isopropanol. The microbial organisms provided advantageously enhance the production of substrates and/or pathway intermediates for the production of chain length specific fatty alcohols, fatty aldehydes, fatty acids or isopropanol. In some aspects, the microbial organisms of the invention have select gene disruptions or enzyme attenuations that increase production of fatty alcohols, fatty aldehydes or fatty acids. The invention additionally provides methods of using the above microbial organisms to produce a fatty alcohol, a fatty aldehyde, a fatty acid or isopropanol.

Abstract translation: 本发明提供具有甲醛固定通道，甲酸同化途径和/或与脂肪醇，脂肪醛，脂肪酸或异丙醇途径组合的甲醇代谢途径的非天然存在的微生物生物，其中所述微生物有选择地产生 脂肪醇，脂肪醛或指定长度的脂肪酸或异丙醇。 提供的微生物有利地增强了用于生产链长特异性脂肪醇，脂肪醛，脂肪酸或异丙醇的底物和/或途径中间体的生产。 在一些方面，本发明的微生物有选择性的基因破坏或酶衰减，其增加脂肪醇，脂肪醛或脂肪酸的产生。 本发明还提供了使用上述微生物生产脂肪醇，脂肪醛，脂肪酸或异丙醇的方法。