Compositions and methods for the biosynthesis of 1,4-butanediol and its precursors

A non-naturally occurring bacterial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (1,4-BDO) biosynthetic pathways, said pathways comprising exogenous nucleic acids encoding a) an α-ketoglutarate decarboxylase, said enzyme converting α-ketoglutarate to succinic semialdehyde, or an α-ketoglutarate dehydrogenase, said enzyme converting α-ketoglutarate to succinyl-CoA, and a CoA-dependent succinic semialdehyde dehydrogenase, said enzyme converting succinyl-CoA to succinic semialdehyde, or a glutamate:succinate semialdehyde transaminase, said enzyme converting α-ketoglutarate to succinic semialdehyde, and a glutamate decarboxylase, said enzyme converting glutamate to 4-aminobutyrate;

• b) a 4-hydroxybutanoate dehydrogenase, said enzyme converting succinic semialdehyde to 4-hydroxybutanoic acid;
• c) a 4-hydroxybutyryl-CoA:acetyl-CoA transferase, said enzyme converting 4-hydroxybutanoic acid to 4-hydroxybutyryl-CoA, or a butyrate kinase and a phosphotransbutyrylase, said enzymes converting 4-hydroxybutanoic acid to 4-hydroxybutyrylphosphate and 4-hydroxybutyrylphosphate to 4-hydroxybutyryl-CoA, respectively;
• d) an aldehyde dehydrogenase, said enzyme converting 4-hydroxybutyryl-CoA to 4-hydroxybutyraldehyde, and e) an alcohol dehydrogenase, said enzyme converting 4-hydroxybutyraldehyde to 1,4-butanediol, wherein said exogenous nucleic acids are expressed in sufficient amounts to produce 1,4-butanediol (1,4-BDO).