COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS

    公开(公告)号:US20090075351A1

    公开(公告)日:2009-03-19

    申请号:US12049256

    申请日:2008-03-14

    IPC分类号: C12N1/21 C12P7/52 C12P7/18

    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 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.

    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS
    5.
    发明申请
    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 有权
    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

    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。

    Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors
    9.
    发明授权
    Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors 有权
    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:US08067214B2

    公开(公告)日:2011-11-29

    申请号:US12049256

    申请日:2008-03-14

    IPC分类号: C12P7/18 C12N1/21

    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。