Transamination and Reductive Amination

Æ-Keto acids can be reductively aminated to Æ-amino acids via amino acid dehydrogenase catalysis, with NAD(P)H as cofactor. The nitrogen source for the amine functionality is ammonia, the least expensive source. Regeneration of the co-factor NAD(P)+ back to NAD(P)H is required for synthesis and is commonly afforded via formate dehydrogenase catalyzed oxidation of formate to carbon dioxide or glucose dehydrogenase catalyzed oxidation of glucose to gluconic acid. While the equilibrium position strongly favors formation of amino acids from keto acids, amino acids can also be deaminated to keto acids if the coupled regeneration reactions provide the driving force. Recently, amine dehydrogenases, which reductively aminate ketones to amines, have been developed via protein engineering. Both amino acid and amine dehydrogenases are exquisitely enantioselective, leading to (S)or, less frequently, to (R)-amino acids or to (R)-amines.