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
    8.
    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。