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1. 发明申请

WO2010141920A2 MICROORGANISMS FOR THE PRODUCTION OF 1,4-BUTANEDIOL AND RELATED METHODS 审中-公开
标题翻译：用于生产1,4-丁二醇的微生物及相关方法
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
申请人： 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
发明人： 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分类号： C12P7/18
CPC分类号： C12P7/18 , C12N9/0006 , C12N9/0008 , C12N9/001 , C12N9/13 , C12N9/16 , C12N9/88 , C12N9/93 , C12N15/52
摘要： 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.
摘要翻译：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。

2. 发明申请

WO2009023493A1 METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF 1,4-BUTANEDIOL 审中-公开
标题翻译：用于1,4-丁二醇的生长联合生产的方法和有机体
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
申请人： GENOMATICA, INC. , BURGARD, Anthony, P. , VAN DIEN, Stephen, J. , BURK, Mark, J.
发明人： BURGARD, Anthony, P. , VAN DIEN, Stephen, J. , BURK, Mark, J.
IPC分类号： C12N15/52 , C12P7/18 , C12N1/00
CPC分类号： C12P7/18 , B01D3/002 , C12N9/0006
摘要： 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.
摘要翻译：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。

3. 发明申请

WO2009045637A2 METHODS FOR THE SYNTHESIS OF OLEFINS AND DERIVATIVES 审中-公开
标题翻译：用于合成烯烃和衍生物的方法
公开(公告)号：WO2009045637A2
公开(公告)日：2009-04-09
申请号：PCT/US2008/072679
申请日：2008-08-08
申请人： GENOMATICA, INC. , BURK, Mark, J. , PHARKYA, Priti , VAN DIEN, Stephen, J. , BURGARD, Anthony, P. , SCHILLING, Christopher, H.
发明人： BURK, Mark, J. , PHARKYA, Priti , VAN DIEN, Stephen, J. , BURGARD, Anthony, P. , SCHILLING, Christopher, H.
IPC分类号： C07C51/347 , C07C67/333 , C12P7/46 , C07C57/04 , C07C69/54
CPC分类号： C07C51/353 , C07C51/38 , C07C57/04 , C07C67/08 , C07C67/32 , C07C67/333 , C12P7/40 , C12P7/46 , C12P7/62 , Y02P20/125 , C07C69/60 , C07C69/54
摘要： 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.
摘要翻译：本发明提供了一种生产丙烯酸的方法。该方法包括使富马酸与足够量的乙烯在交叉复分解转化催化剂存在下接触以每摩尔富马酸产生约2摩尔丙烯酸。还提供了丙烯酸酯。该方法包括使富马酸二酯与足够量的乙烯在交叉复分解转化催化剂存在下接触，以每摩尔富马酸二酯产生约2摩尔丙烯酸酯。提供了一种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复分解转化相结合。还提供丙烯酸和丙烯酸酯生产。

4. 发明申请

WO2009045637A9 METHODS FOR THE SYNTHESIS OF OLEFINS AND DERIVATIVES 审中-公开
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
申请人： GENOMATICA, INC. , BURK, Mark, J. , PHARKYA, Priti , VAN DIEN, Stephen, J. , BURGARD, Anthony, P. , SCHILLING, Christopher, H.
发明人： BURK, Mark, J. , PHARKYA, Priti , VAN DIEN, Stephen, J. , BURGARD, Anthony, P. , SCHILLING, Christopher, H.
IPC分类号： C07C51/347 , C07C67/333 , C12P7/46 , C07C57/04 , C07C69/54
摘要： 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.

5. 发明申请

WO2009045637A3 METHODS FOR THE SYNTHESIS OF ACRYLIC ACID AND DERIVATIVES FROM FUMARIC ACID 审中-公开
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
申请人： GENOMATICA, INC. , BURK, Mark, J. , PHARKYA, Priti , VAN DIEN, Stephen, J. , BURGARD, Anthony, P. , SCHILLING, Christopher, H.
发明人： BURK, Mark, J. , PHARKYA, Priti , VAN DIEN, Stephen, J. , BURGARD, Anthony, P. , SCHILLING, Christopher, H.
IPC分类号： C07C51/347 , C07C67/333 , C12P7/46 , C07C57/04 , C07C69/54
摘要： 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.

6. 发明申请

WO2008091627A2 METHODS AND ORGANISMS FOR GROWTH-COUPLED PRODUCTION OF 3-HYDROXYPROPIONIC ACID 审中-公开
标题翻译：生长3-羟基丙酸生产的方法和机理
公开(公告)号：WO2008091627A2
公开(公告)日：2008-07-31
申请号：PCT/US2008/000861
申请日：2008-01-22
申请人： GENOMATICA, INC. , BURGARD, Anthony, P. , VAN DIEN, Stephen, J.
发明人： BURGARD, Anthony, P. , VAN DIEN, Stephen, J.
IPC分类号： C12N1/00
CPC分类号： C12N15/52 , C12N9/00 , C12P7/42
摘要： The invention provides a non-naturally occurring microorganism having one or more gene disruptions, the one or more gene disruptions occurring in genes encoding an enzyme obligatory coupling 3-hydroxypropionic acid production to growth of the microorganism when the gene disruption reduces an activity of the enzyme, whereby the one or more gene disruptions confers stable growth-coupled production of 3-hydroxypropionic acid onto the non-naturally occurring microorganism. Also provided is a non-naturally occurring microorganism comprising a set of metabolic modifications obligatory coupling 3-hydroxypropionic acid production to growth of the microorganism, the set of metabolic modifications having disruption of one or more genes including: (a) the set of genes selected from: (1) adhE, ldhA, pta-ackA; (2) adhE, ldhA, frdABCD; (3) adhE, ldhA, frdABCD, ptsG; (4) adhE, ldhA, frdABCD, pntAB; (5) adhE, ldhA, fumA, fumB, fumC; (6) adhE, ldhA, fumA, fumB, fumC, pntAB; (7) pflAB, ldhA, or (8) adhE, ldhA, pgi in a microorganism utilizing an anaerobic β-alanine 3-HP precursor pathway; (b) the set of genes selected from: (1) tpi, zwf; (2) tpi, ybhE; (3) tpi, gnd; (4) fpb, gapA; (5) pgi, edd, or (6) pgi, eda in a microorganism utilizing an aerobic glycerol 3-HP precursor pathway; (c) the set of genes selected from: (1) eno ; (2) yibO ; (3) eno , atpH, or other atp subunit, or (4) yibO , atpH , or other atp subunit, in a microorganism utilizing a glycerate 3-HP precursor pathway, or an ortholog thereof, wherein the microorganism exhibits stable growth- coupled production of 3-hydroxypropionic acid. The disruptions can be complete gene disruptions and the non-naturally occurring organisms can include a variety of prokaryotic or eukaryotic microorganisms. A method of producing a non-naturally occurring microorganism having stable growth-coupled production of 3-hydroxypropionic acid is further provided. The method includes: (a) identifying in silico a set of metabolic modifications requiring 3-hydroxypropionic acid production during exponential growth, and (b) genetically modifying a microorganism to contain the set of metabolic modifications requiring 3-hydroxypropionic acid production.
摘要翻译：本发明提供了一种具有一个或多个基因破坏的非天然存在的微生物，当基因破坏降低酶的活性时，编码酶强制性偶合3-羟基丙酸产生的微生物生长的基因中发生的一种或多种基因破坏由此一个或多个基因破坏赋予非天然存在的微生物上3-羟基丙酸的稳定生长偶联产生。还提供了非天然存在的微生物，其包含一系列代谢修饰，其强制性将3-羟基丙酸生产偶联至微生物生长，该组代谢修饰具有破坏一个或多个基因，包括：（a）所选择的一组基因来自：（1）adhE，ldhA，pta-ackA; （2）adhE，ldhA，frdABCD; （3）adhE，ldhA，frdABCD，ptsG; （4）adhE，ldhA，frdABCD，pntAB; （5）adhE，ldhA，fumA，fumB，fumC; （6）adhE，ldhA，fumA，fumB，fumC，pntAB; （7）pflAB，ldhA或（8）adhE，ldhA，pgi在使用厌氧β-丙氨酸3-HP前体途径的微生物中; （b）选自以下的一组基因：（1）tpi，zwf; （2）tpi，ybhE; （3）tpi，gnd; （4）fpb，gapA; （5）pgi，edd或（6）pgi，eda在利用有氧甘油3-HP前体途径的微生物中; （c）选自以下的一组基因：（1）eno; （2）yibo; （3）eno，atpH或其他atp亚基，或（4）yibO，atpH或其他atp亚基，使用甘油3-HP前体途径的微生物或其直系同源物，其中所述微生物表现出稳定的生长耦合生产3-羟基丙酸。破坏可能是完全的基因破坏，非天然存在的生物体可以包括多种原核或真核微生物。还提供了一种生产具有稳定的3-羟基丙酸的生长偶联生产的非天然存在的微生物的方法。该方法包括：（a）在指数生长过程中，以计算机识别需要3-羟基丙酸生成的一组代谢修饰，和（b）遗传修饰微生物以包含需要3-羟基丙酸生产的一组代谢修饰。

7. 发明申请

WO2007030830A2 METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF SUCCINATE 审中-公开
标题翻译：生长联合生产的方法和机制
公开(公告)号：WO2007030830A2
公开(公告)日：2007-03-15
申请号：PCT/US2006/035569
申请日：2006-09-08
申请人： GENOMATICA, INC. , BURGARD, Anthony, P. , VAN DIEN, Stephen, J.
发明人： BURGARD, Anthony, P. , VAN DIEN, Stephen, J.
IPC分类号： C12N1/21
CPC分类号： C12N15/52 , C12N9/0006 , C12N9/001 , C12N9/1029 , C12N9/1205 , C12N9/1217 , C12N9/14 , C12P7/46
摘要： The invention provides a non-naturally occurring microorganism comprising one or more gene disruptions encoding an enzyme associated with growth-coupled production of succinate when an activity of the enzyme is reduced, whereby the one or more gene disruptions confers stable growth-coupled production of succinate onto the non- naturally occurring microorganism. Also provided is a non-naturally occurring microorganism comprising a set of metabolic modifications obligatory coupling succinate production to growth of the microorganism, the set of metabolic modifications comprising disruption of one or more genes selected from the set of genes comprising: (a) adhE, ldhA ; (b) adhE, ldhA, ackA-pta ; (c) pfl, ldhA ; (d) pfl, IdhA, adhE ; (e) ackA-pta , pykF, atpF, sdhA ; (f) ackA-pta, pykF, ptsG , or (g) ackA-pta, pykF, ptsG, adhE, IdhA , or an ortholog thereof, wherein the microorganism exhibits stable growth-coupled production of succinate. Additionally provided is a non-naturally occurring microorganism having the genes encoding the metabolic modification (e) ackA-pta, pykF , atpF, sdhA that further includes disruption of at least one gene selected from pykA, atpH , sdhB or dhaKLM ; a non-naturally occurring microorganism having the genes encoding the metabolic modification (f) ackA-pta, pykF, ptsG that further includes disruption of at least one gene selected from pykA or dhaKLM , or a non-naturally occurring microorganism having the genes encoding the metabolic modification (g) ackA-pta, pykF , ptsG, adhE, IdhA that further includes disruption of at least one gene selected from pykA or dhaKLM . The disruptions can be complete gene disruptions and the non-naturally occurring organisms can include a variety of prokaryotic or eukaryotic microorganisms. A method of producing a non-naturally occurring microorganism having stable growth- coupled production of succinate also is provided. The method includes: (a) identifying in silico a set of metabolic modifications requiring succinate production during exponential growth, and (b) genetically modifying a microorganism to contain the set of metabolic modifications requiring succinate production.
摘要翻译：本发明提供了一种非天然存在的微生物，当酶的活性降低时，其包含一种或多种编码与琥珀酸生长偶联产生相关的酶的基因破坏，由此一个或多个基因破坏赋予琥珀酸稳定的生长偶联产生到非天然存在的微生物。还提供了一种非天然存在的微生物，其包含一系列代谢修饰，强制性将琥珀酸生产偶联到微生物的生长中，该组代谢修饰包括从一组基因中选出的一种或多种基因的破坏，包括：（a）adhE，的ldhA; （b）adhE，ldhA，ackA-pta; （c）pfl，ldhA; （d）pfl，IdhA，adhE; （e）ackA-pta，pykF，atpF，sdhA; （f）ackA-pta，pykF，ptsG或（g）ackA-pta，pykF，

8. 发明申请

WO2012177619A2 MICROORGANISMS FOR PRODUCING 1,3-BUTANEDIOL AND METHODS RELATED THERETO 审中-公开
标题翻译：用于生产1,3-丁二醇的微生物及其相关方法
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
申请人： GENOMATICA, INC. , BURGARD, Anthony, P. , BURK, Mark, J. , OSTERHOUT, Robin, E. , SUN, Jun , PHARKYA, Priti
发明人： BURGARD, Anthony, P. , BURK, Mark, J. , OSTERHOUT, Robin, E. , SUN, Jun , PHARKYA, Priti
IPC分类号： C12N1/21 , C12P7/18
CPC分类号： C12P7/18 , C12N15/52
摘要： 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.
摘要翻译：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。

9. 发明申请

WO2012135789A2 MICROORGANISMS FOR PRODUCING METHACRYLIC ACID AND METHACRYLATE ESTERS AND METHODS RELATED THERETO 审中-公开
标题翻译：生产甲基丙烯酸和甲基丙烯酸酯的微生物及其相关方法
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
申请人： GENOMATICA, INC. , BURK, Mark, J. , BURGARD, Anthony, P. , OSTERHOUT, Robin, E. , SUN, Jun , PHARKYA, Priti
发明人： BURK, Mark, J. , BURGARD, Anthony, P. , OSTERHOUT, Robin, E. , SUN, Jun , PHARKYA, Priti
IPC分类号： C12P7/40
CPC分类号： C12P7/40 , C12P7/42 , C12P7/62 , C12P19/32
摘要： 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.
摘要翻译：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。

10. 发明申请

WO2012018624A3 MICROORGANISMS AND METHODS FOR THE BIOSYNTHESIS OF AROMATICS, 2,4-PENTADIENOATE AND 1,3-BUTADIENE 审中-公开
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
申请人： GENOMATICA, INC. , OSTERHOUT, Robin, E. , BURGARD, Anthony, P. , PHARKYA, Priti , BURK, Mark, J.
发明人： OSTERHOUT, Robin, E. , BURGARD, Anthony, P. , PHARKYA, Priti , BURK, Mark, J.
IPC分类号： C12P5/00 , C12P5/02 , C12P7/40
摘要： 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.

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