Amine dehydrogenases: Current status and potential value for chiral amine synthesis

Chiral amines are crucial precursors of various pharmaceutical drugs, fine chemicals, and bioactive molecules. Amine dehydrogenases (AmDHs) have attracted increasing attention for chiral-amine synthesis, with great potentials to overcome the shortcomings of conventional chemical methods. However, the narrow substrate scope and expensive cofactors required can be quite challenging for the AmDHs. A number of attempts have been made to improve AmDHs and their reaction systems. The available AmDHs are mainly obtained by the discovery of the natural AmDHs and the engineering of amino acid dehydrogenases. In this review, recent advances in the structures, mechanisms, and mutation studies of AmDHs are discussed in detail, facilitating the engineering of AmDHs more efficiently. Besides, various enzyme-coupled and immobilization strategies have been designed to optimize the AmDH-catalyzed reaction systems, not only achieving the cofactor regeneration but also enhancing the productivity. Future research directions for improving the performance and reaction system of AmDHs are evaluated. • Introduced the structural and mechanistic advances of amine dehydrogenases (AmDHs) • Change of active pockets before and after mutation were compared by molecular docking • Discussed and prospected the strategies to optimize the AmDH-catalyzed system • Prospected the current limitations and potential solutions of AmDHs in the future Optically pure chiral amines are a kind of important chiral substance that are widely used in the synthesis of drugs, natural products, fine chemicals, and other compounds. As a new biocatalyst, amine dehydrogenases (AmDHs) catalyze the asymmetric formation of chiral amines by ketones. The purpose of this review is to provide a general overview of reported types of natural and engineered AmDHs, their catalytic mechanisms, and the design and application of bioreactors. The uniqueness and indispensability of this review relative to other published reviews or perspectives is a particular focus on the active centers of mutants and simulating the changes of active pockets through molecular docking. The concluding remarks are presented with perspectives on future challenges and strategies in this burgeoning research area. This review might supply guidance for the design of novel, highly active, and substrate-selective AmDHs and novel bioreactors. Amine dehydrogenases (AmDHs), as new biocatalysts for the asymmetric synthesis of chiral amines, have attracted much attention in recent years. In this review, we focus on the structural and mechanistic advances of AmDHs regarding how substrates are bound and catalyzed as well as the functions of the key residues crucial for the enzymatic properties. Furthermore, the strategies to optimize the AmDH-catalyzed system to overcome the limitations that may be encountered in the application of AmDHs are discussed.