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    METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF 1,4-BUTANEDIOL
    8.
    发明申请
    METHODS AND ORGANISMS FOR THE GROWTH-COUPLED PRODUCTION OF 1,4-BUTANEDIOL 审中-公开
    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

    Applicant: GENOMATICA, INC. ,  BURGARD, Anthony, P. ,  VAN DIEN, Stephen, J. ,  BURK, Mark, J.

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

    IPC: C12N15/52 ,  C12P7/18 ,  C12N1/00

    CPC classification number: C12P7/18 ,  B01D3/002 ,  C12N9/0006

    Abstract: 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.

    Abstract translation: 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。

    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS
    10.
    发明申请
    COMPOSITIONS AND METHODS FOR THE BIOSYNTHESIS OF 1,4-BUTANEDIOL AND ITS PRECURSORS 审中-公开
    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：WO2008115840A2

    公开(公告)日：2008-09-25

    申请号：PCT/US2008/057168

    申请日：2008-03-14

    Applicant: GENOMATICA, INC. ,  BURK, Mark, J. ,  VAN DIEN, Stephen, J. ,  BURGARD, Anthony ,  NIU, Wei

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

    IPC: C12N1/21

    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 A- 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 A- 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.

    Abstract translation: 本发明提供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 表达量足以生产1,4-丁二醇（BDO）。 另外提供了用于生产4-HB的方法。 所述方法包括培养具有4-羟基丁酸（4-HB）生物合成途径的非天然存在的微生物生物，其包含至少一种编码4-羟基丁酸脱氢酶的外源核酸，琥珀酰辅酶A合成酶，辅酶A依赖性琥珀酸半醛脱氢酶或 - 酮戊二酸脱羧酶在充分的厌氧条件下持续足够的时间以产生单体的4-羟基丁酸（4-HB）。 进一步提供一种生产BDO的方法。 该方法包括培养非天然存在的微生物生物催化剂，其包含具有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，所述途径包括至少一种编码4- 羟基丁酸脱氢酶，琥珀酰辅酶A合成酶，CoA依赖性琥珀酸脱氢酶，4-羟基丁酸酯：CoA转移酶，4-羟基丁酸酯激酶，磷酸转移羟基丁酸酶，α-酮戊二酸脱羧酶，醛脱氢酶，醇脱氢酶或醛/醇脱氢酶， 时间来生产1,4-丁二醇（BDO）。 4-HB和/或BDO产物可以分泌到培养基中。

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