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 .alpha.-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, .alpha.-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
.alpha.-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,
.alpha.-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.