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1. 发明授权

US08889399B2 Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors 有权
标题翻译： 1,4-丁二醇及其前体的生物合成的组合物和方法
公开(公告)号：US08889399B2
公开(公告)日：2014-11-18
申请号：US13286135
申请日：2011-10-31
申请人： Mark J. Burk , Stephen J. Van Dien , Anthony P. Burgard , Wei Niu
发明人： Mark J. Burk , Stephen J. Van Dien , Anthony P. Burgard , Wei Niu
IPC分类号： C12N1/20 , C12P7/18 , C12P7/42 , C12N9/04 , C12N9/88 , C12N9/00 , C12N9/02 , C12P7/52 , C12P17/04
CPC分类号： 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
摘要： 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.
摘要翻译：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。

2. 发明授权

US08673601B2 Methods and organisms for growth-coupled production of 3-hydroxypropionic acid 有权
标题翻译：用于3-羟基丙酸生长偶联生产的方法和生物
公开(公告)号：US08673601B2
公开(公告)日：2014-03-18
申请号：US12018129
申请日：2008-01-22
申请人： Anthony P. Burgard , Stephen J. Van Dien
发明人： Anthony P. Burgard , Stephen J. Van Dien
IPC分类号： C12P7/52 , C12N9/00 , C12N1/20 , C12N15/00 , C07H21/04
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. 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稳定的3-羟基丙酸生长偶联产生。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。

3. 发明申请

US20140030779A1 MICROORGANISMS AND METHODS FOR PRODUCTION OF 4-HYDROXYBUTYRATE, 1,4-BUTANEDIOL AND RELATED COMPOUNDS 有权
标题翻译：用于生产4-羟基丁酸酯，1,4-丁二醇和相关化合物的微生物和方法
公开(公告)号：US20140030779A1
公开(公告)日：2014-01-30
申请号：US13908907
申请日：2013-06-03
申请人： Priti PHARKYA , Anthony P. BURGARD , Stephen J. VAN DIEN , Robin E. OSTERHOUT , Mark J. BURK , John D. TRAWICK , Michael P. KUCHINSKAS , Brian STEER
发明人： Priti PHARKYA , Anthony P. BURGARD , Stephen J. VAN DIEN , Robin E. OSTERHOUT , Mark J. BURK , John D. TRAWICK , Michael P. KUCHINSKAS , Brian STEER
IPC分类号： C12P7/42 , C12N15/63
CPC分类号： C12N1/20 , C07C31/207 , C07C59/01 , C08G18/284 , C08G18/3206 , C08G63/06 , C08G63/16 , C08G63/181 , C08G69/02 , C12N9/18 , C12N15/52 , C12N15/63 , C12P7/18 , C12P7/42 , C12Y301/01 , Y02P20/52
摘要： The invention provides non-naturally occurring microbial organisms having a 4-hydroxybutyrate pathway and being capable of producing 4-hydroxybutyrate, wherein the microbial organism comprises one or more genetic modifications. The invention additionally provides methods of producing 4-hydroxybutyrate or related products using the microbial organisms.
摘要翻译：本发明提供具有4-羟基丁酸途径并且能够产生4-羟基丁酸酯的非天然存在的微生物生物，其中微生物生物体包含一种或多种遗传修饰。本发明另外提供了使用微生物生物制备4-羟基丁酸酯或相关产品的方法。

4. 发明授权

US08455683B2 Methods for the synthesis of olefins and derivatives 有权
标题翻译：合成烯烃和衍生物的方法
公开(公告)号：US08455683B2
公开(公告)日：2013-06-04
申请号：US13219423
申请日：2011-08-26
申请人： Mark J. Burk , Priti Pharkya , Stephen J. Van Dien , Anthony P. Burgard , Christophe H. Schilling
发明人： Mark J. Burk , Priti Pharkya , Stephen J. Van Dien , Anthony P. Burgard , Christophe H. Schilling
IPC分类号： C07C57/04 , C12P7/40
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。

5. 发明授权

US08357520B2 Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors 有权
公开(公告)号：US08357520B2
公开(公告)日：2013-01-22
申请号：US13348564
申请日：2012-01-11
申请人： Mark J. Burk , Stephen J. Van Dien , Anthony P. Burgard , Wei Niu
发明人： Mark J. Burk , Stephen J. Van Dien , Anthony P. Burgard , Wei Niu
IPC分类号： C12P7/18 , C12N1/21
CPC分类号： 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
摘要： 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 are methods for the production of 4-HB and BDO.

6. 发明申请

US20120122171A1 COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 有权
标题翻译： 1,4-丁二醇及其前体的生物合成的组合物和方法
公开(公告)号：US20120122171A1
公开(公告)日：2012-05-17
申请号：US13348564
申请日：2012-01-11
申请人： Mark J. Burk , Stephen J. Van Dien , Anthony P. Burgard , Wei Niu
发明人： Mark J. Burk , Stephen J. Van Dien , Anthony P. Burgard , Wei Niu
IPC分类号： C12P7/18 , C12N1/19 , C12N1/15 , C12N1/21
CPC分类号： 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
摘要： 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 are methods for the production of 4-HB and BDO.
摘要翻译：本发明提供了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，其具有至少一种编码4-羟基丁酸脱氢酶的外源核酸，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸半醛脱氢酶或α-酮戊二酸脱羧酶，其中外源核酸以足够的量表达以产生单体4-羟基丁酸（4-HB）。还提供了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）和1,4-丁二醇（BDO）生物合成途径的微生物生物，该途径包括至少一种编码4-羟基丁酸脱氢酶的外源核酸，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸半醛脱氢酶，4-羟基丁酸酯：CoA转移酶，4-丁酸酯激酶，磷酸转移酶，α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶，其中外源核酸为以足够的量表示产生1,4-丁二醇（BDO）。另外提供了一种生产4-HB和BDO的方法。

7. 发明授权

US08129169B2 Microorganisms for the production of 1,4-butanediol and related methods 有权
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：US08129169B2
公开(公告)日：2012-03-06
申请号：US12794700
申请日：2010-06-04
申请人： Stephen J. Van Dien , Anthony P. Burgard , Robert Haselbeck , Catherine J. Pujol-Baxley , Wei Niu , John D. Trawick , Harry Yim , Mark J. Burk , Robin E. Osterhout , Jun Sun
发明人： Stephen J. Van Dien , Anthony P. Burgard , Robert Haselbeck , Catherine J. Pujol-Baxley , Wei Niu , John D. Trawick , Harry Yim , Mark J. Burk , Robin E. Osterhout , Jun Sun
IPC分类号： C12N1/21
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：本发明提供了包含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并进一步优化用于BDO的表达。本发明还提供了使用这种微生物生产BDO的方法。

8. 发明授权

US07947483B2 Methods and organisms for the growth-coupled production of 1,4-butanediol 有权
标题翻译：用于1,4-丁二醇生长偶联生产的方法和生物
公开(公告)号：US07947483B2
公开(公告)日：2011-05-24
申请号：US11891602
申请日：2007-08-10
申请人： Anthony P. Burgard , Stephen J. Van Dien , Mark Burk
发明人： Anthony P. Burgard , Stephen J. Van Dien , Mark Burk
IPC分类号： C12N1/20 , C12N1/21 , C12Q1/68 , C12P7/18
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 the one 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：本发明提供了包含一种或多种基因破坏的非天然存在的微生物，所述一个或多个基因破坏发生在编码需要将1,4-丁二醇生产偶联以生产微生物的酶的基因发生在基因破坏时降低活性该酶，其中一个或多个基因破坏赋予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。

9. 发明申请

US20080199926A1 Methods and Organisms for Growth-Coupled Production of 3-Hydroxypropionic Acid 有权
公开(公告)号：US20080199926A1
公开(公告)日：2008-08-21
申请号：US12018129
申请日：2008-01-22
申请人： Anthony P. Burgard , Stephen J. Van Dien
发明人： Anthony P. Burgard , Stephen J. Van Dien
IPC分类号： C12P7/52 , C12N1/20 , C12N1/00 , C12N15/74
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.

10. 发明申请

US20090047719A1 Methods and organisms for the growth-coupled production of 1,4-butanediol 有权
标题翻译：用于1,4-丁二醇生长偶联生产的方法和生物
公开(公告)号：US20090047719A1
公开(公告)日：2009-02-19
申请号：US11891602
申请日：2007-08-10
申请人： Anthony P. Burgard , Stephen J. Van Dien , Mark Burk
发明人： Anthony P. Burgard , Stephen J. Van Dien , Mark Burk
IPC分类号： C12P7/18 , C12N1/00 , C12N1/20 , C12N1/16 , C12N1/14
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：本发明提供了包含一种或多种基因破坏的非天然存在的微生物，所述一个或多个基因破坏发生在编码需要将1,4-丁二醇生产偶联以生产微生物的酶的基因发生在基因破坏时降低活性该酶，其中一种或多种基因破坏赋予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。

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