Enzymatic cascade systems for D-amino acid synthesis: progress and perspectives

D -amino acids, different from the ubiquitous L -amino acids, are recognized as the “unnatural” amino acids. The applications of D -amino acids have drawn increasing interest from researchers in recent years, and D -amino acids are widely used in various industries, including for food products, pharmaceuticals, and agricultural chemicals. Inspired by the prevalent applications, many synthetic methods for D -amino acids have been developed, which are mainly divided into chemical synthetic methods and biosynthetic methods. Chemical synthesis of D -amino acids has a variety of disadvantages such as multiple reaction steps, low yields, low reaction rates, and difficulties in product extraction. Thus, biosynthetic methods utilizing enzymes are attracting increasing attention because they are more energy-saving and environmentally friendly compared to traditional chemical synthesis. Among all enzymatic methods, multi-enzymatic cascade catalytic methods have significant advantages, such as lower costs, no need for intermediate separation, and higher catalytic efficiency, which is ascribed to the spatial proximity of biocatalysts. In this review, advances in multi-enzyme cascade catalytic systems as well as chemo-enzymatic approaches to synthesize D -amino acids are discussed.