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    MICROORGANISMS AND METHODS FOR PRODUCING (3R)-HYDROXYBUTYL (3R)-HYDROXYBUTYRATE
    202.
    发明申请
    MICROORGANISMS AND METHODS FOR PRODUCING (3R)-HYDROXYBUTYL (3R)-HYDROXYBUTYRATE 审中-公开
    （3R） - 羟基丁酸（3R） - 羟基丁酸酯的微生物和方法

    公开(公告)号：US20160108442A1

    公开(公告)日：2016-04-21

    申请号：US14893510

    申请日：2014-05-23

    Applicant: Genomatica, Inc.

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

    IPC: C12P7/62 ,  C07C69/675 ,  C12N15/52 ,  C12R1/01 ,  C12R1/645

    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)-1,3-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（3R） - （3R） - 羟基丁酸生产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（3R） - 羟基丁酸（3R） - 羟基丁酸生产和分离（3R） - 羟基丁酸酯的方法和方法，以及具有（3R） - 羟基丁基（3R） - 羟基丁酸酯的各种组合物。 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。

    Microorganisms for Producing 1,3-Butanediol and Methods Related Thereto
    204.
    发明申请
    Microorganisms for Producing 1,3-Butanediol and Methods Related Thereto 审中-公开
    用于生产1,3-丁二醇的微生物及其相关方法

    公开(公告)号：US20160076060A1

    公开(公告)日：2016-03-17

    申请号：US14692630

    申请日：2015-04-21

    Applicant: Genomatica, Inc.

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

    IPC: 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-BDO）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。

    METHODS AND ORGANISMS FOR UTILIZING SYNTHESIS GAS OR OTHER GASEOUS CARBON SOURCES AND METHANOL
    205.
    发明申请
    METHODS AND ORGANISMS FOR UTILIZING SYNTHESIS GAS OR OTHER GASEOUS CARBON SOURCES AND METHANOL 审中-公开

    公开(公告)号：US20160053288A1

    公开(公告)日：2016-02-25

    申请号：US14700103

    申请日：2015-04-29

    Applicant: Genomatica, Inc.

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

    IPC: C12P7/18

    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.

    MICROORGANISMS AND METHODS FOR THE PRODUCTION OF CAPROLACTONE
    206.
    发明申请
    MICROORGANISMS AND METHODS FOR THE PRODUCTION OF CAPROLACTONE 审中-公开
    用于生产CAPROLACTONE的微生物和方法

    公开(公告)号：US20150353975A1

    公开(公告)日：2015-12-10

    申请号：US14596072

    申请日：2015-01-13

    Applicant: Genomatica, Inc.

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

    IPC: C12P17/08 ,  C07D313/04 ,  C12N15/70

    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: 本发明提供了非天然存在的含有己内酯途径的微生物，其具有至少一种编码丁二烯途径酶的外源核酸，其表达量足以产生己内酯。 本发明另外提供了使用这种微生物生物体来制备己内酯的方法，该方法是在条件和足够的时间内培养含本文所述的己内酯途径的非天然存在的微生物生物产生己内酯。

    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS
    207.
    发明申请
    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 审中-公开

    公开(公告)号：US20150267229A1

    公开(公告)日：2015-09-24

    申请号：US14530530

    申请日：2014-10-31

    Applicant: GENOMATICA, INC.

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

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

    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.

    ORGANISMS FOR THE PRODUCTION OF CYCLOHEXANONE
    210.
    发明申请
    ORGANISMS FOR THE PRODUCTION OF CYCLOHEXANONE 审中-公开
    生产环己酮的有机体

    公开(公告)号：US20140356919A1

    公开(公告)日：2014-12-04

    申请号：US14172079

    申请日：2014-02-04

    Applicant: Genomatica, Inc.

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

    IPC: C12P7/26 ,  C12N15/52 ,  C12N15/70

    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-1-carboxylate decarboxylase and an enzyme selected from a 2-ketocyclohexane-1-carboxyl-CoA hydrolase (acting on thioester), a 2-ketocyclohexane-1-carboxyl-CoA transferase, and a 2-ketocyclohexane-1-carboxyl-CoA synthetase. A pathway includes an enzyme selected from a 6-ketocyclohex-1-ene-1-carboxyl-CoA hydrolase (acting on C—C bond), a 6-ketocyclohex-1-ene-1-carboxyl-CoA synthetase, a 6-ketocyclohex-1-ene-1-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-1-carboxyl-CoA synthetase, a 2-ketocyclohexane-1-carboxyl-CoA transferase, a 2-ketocyclohexane-1-carboxyl-CoA hydrolase (acting on thioester), a 2-ketocyclohexane-1-carboxylate decarboxylase, and a cyclohexanone dehydrogenase. A pathway includes an adipate semialdehyde dehydratase, a cyclohexane-1,2-diol dehydrogenase, and a cyclohexane-1,2-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C-C键），2-酮环己烷-1-羧酸脱羧酶和选自2-酮环己烷-1-羧基-CoA水解酶的酶（作用 在硫酯上），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C-C键）的酶，6-酮环己-1-烯-1-羧基-CoA合成酶，6- 酮酮环己-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-酮环己-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-氧代邻苯二甲酸脱羧酶，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。

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