Asymmetric Reductive Amination of Structurally Diverse Ketones with an Engineered Amine Dehydrogenase

Chemical catalysis with an open-boundary catalytic architecture can confer a broad substrate scope but is typically accompanied with non-ideal enantioselectivity. Enzymatic catalysis with a closed-boundary catalytic architecture promises the achievement of quantitative enantioselectivity but generally at the cost of a narrow substrate scope. Herein an engineered amine dehydrogenase has been developed as an exemplary catalytic system for addressing this substrate scope-enantioselectivity dilemma. Asymmetric reductive amination with essentially quantitative enantioselectivity has been demonstrated for structurally diverse, both aromatic and alkyl ketones. Reciprocal conformational adaptation, with complementary matching of conformational flexibility and sterics on both the enzyme and substrate sides, is proposed as an effective working mechanism for ensuring the efficient occurrence of catalysis. The synthetic features showcased herein support the combination of a closed-boundary catalytic architecture and reciprocal conformational adaptation as a generic pathway to simultaneously, a broad substrate scope and quantitative enantioselectivity.