Advances in the Enzymic Synthesis of Unnatural Chiral Amino Acids

Unnatural chiral amino acids (UCAAs), including D-amino acids and noncanonical L-amino acids, are immensely valuable chiral chemicals, which are extensively applied in pharmaceuticals, materials, and fine chemicals. Biosynthesis of UCAAs by enzymes has emerged as a powerful, green, and highly efficient strategy. Amino acid dehydrogenases, which catalyze asymmetric reductive amination of keto acids, represent the most widely employed enzyme for the synthesis of UCAAs. Transaminases, which enable asymmetric transfer of an amino group to keto acids, have also been successfully applied in the synthesis of several noncanonical L-amino acids. Furthermore, catalytic promiscuity of enzyme which considerably expanded the synthetic potential toward diverse UCAAs has been reported. In addition, multienzyme system with cofactor regeneration has significantly improved the synthesis efficiency. This review summarizes recent advances in the in vitro enzymatic synthesis recently published by Chinese researcher. An outlook on AI-driven biocatalysis for the green and sustainable production of UCAAs has been promoted. Emerging tools such as artificial intelligence, machine learning, and high-throughput platforms will further drive the green and efficient synthesis of chiral amino acids.