Development of β-Amino Acid Dehydrogenase for the Synthesis of β-Amino Acids via Reductive Amination of β-Keto Acids

An L-erythro-3,5-diaminohexanoate dehydrogenase from Candidatus Cloacamonas acidaminovorans (3,5-DAHDHcca) was engineered to beta-amino acid dehydrogenase (beta-AADH) by screening a domain scanning mutagenesis library. The best beta-AADH mutant displayed about 200-fold activity toward (R)-beta-homomethionine compared with the wild-type enzyme. (R)-beta-Homomethionine, (R)-beta-phenylalanine, and (S)-beta-aminobutyric acid were obtained via beta-AADH-catalyzed reductive amination of the corresponding beta-keto acids, which were generated from beta-keto-nitriles or beta-keto-esters with nitrilase or lipase. This is the first example of the direct reductive amination of beta-keto acids catalyzed by beta-AADH to give beta-amino acids, opening a new venue for the synthesis of chiral beta-amino acids.