胺脱氢酶催化合成手性胺的机遇与挑战

Opportunities and challenges of amine dehydrogenases for chiral amine synthesis

光学纯的手性胺是一类重要的手性砌块,广泛应用于药物、天然产物、精细化学品等化合物的合成中。手性胺的酶促合成方法因立体选择性高、反应条件温和、反应过程绿色等优点,引起了学术界与工业界的广泛关注。近年来,一类新颖的胺脱氢酶被报道,其能够利用廉价氨作为氨基供体,催化酮的不对称还原胺化,成为一种有潜力的手性胺合成生物催化剂。在胺脱氢酶的发现、分子改造、底物谱拓展、过程强化、多酶级联构建等方面已取得了显著的进展。本文中,笔者对该类酶取得的研究进展进行总结,并预测其未来的研究趋势和应用中面临的机遇与挑战。

Chiral amines are widely present in the structures of bioactive molecules such as pharmaceuticals and natural products.The synthesis of chiral amines through enzyme-catalysis has attracted widespread attention of researchers.Recently,amine dehydrogenases(AmDHs)capable of catalyzing the asymmetric reductive amination of ketones with ammonia,have been reported as a promising class of biocatalysts for accessing optically active chiral amines.Significant progress in the discovery and evolution of AmDHs,expansion of substrate spectrum,optimization of reaction processes,and construction of multi-enzyme cascade,has been achieved in recent years.Herein,we review the recent research advances referring to AmDHs and the future research trends,and discuss the opportunities and challenges of the enzyme for practical synthesis of chiral amines.