Highly Atom Economic Synthesis of d-2-Aminobutyric Acid through an In Vitro Tri-enzymatic Catalytic System.

Abstract

d‐2‐Aminobutyric acid is an unnatural amino acid serving as an important intermediate in pharmaceutical production. Developing a synthetic method that uses cheaper starting materials and produces less by‐product is a pressing demand. A tri‐enzymatic catalytic system, which is composed of l‐threonine ammonia lyase (l‐TAL), d‐amino acid dehydrogenase (d‐AADH), and formate dehydrogenase (FDH), has thus been developed for the synthesis of d‐2‐aminobutyric acid with high optical purity. In this cascade reaction, the readily available l‐threonine serves as the starting material, carbon dioxide and water are the by‐products. d‐2‐Aminobutyric acid was obtained with >90 % yield and >99 % enantioselective excess, even without adding external ammonia, demonstrating that the ammonia from the first reaction can serve as the amino donor for the reductive amination step. This multi‐enzymatic system provides an attractive method with high atomic economy for the synthesis of d‐α‐amino acids from the corresponding l‐α‐amino acids, which are readily produced by fermentation.