还原胺化
化学
亚胺
胺气处理
土曲霉
酮
还原消去
组合化学
环己酮
胺化
基质(水族馆)
催化作用
有机化学
食品科学
海洋学
地质学
作者
Mahima Sharma,Juan Mangas‐Sánchez,Godwin A. Aleku,Sarah L. Montgomery,Jeremy I. Ramsden,Nicholas J. Turner,Gideon Grogan
标识
DOI:10.1021/acscatal.8b03491
摘要
Reductive aminases (RedAms) catalyze the asymmetric reductive amination of ketones with primary amines to give secondary amine products. RedAms have great potential for the synthesis of bioactive chiral amines; however, insights into their mechanism are currently limited. Comparative studies on reductive amination of cyclohexanone with allylamine in the presence of RedAms, imine reductases (IREDs), or NaBH3CN support the distinctive activity of RedAms in catalyzing both imine formation and reduction in the reaction. Structures of AtRedAm from Aspergillus terreus, in complex with NADPH and ketone and amine substrates, along with kinetic analysis of active-site mutants, reveal modes of substrate binding, the basis for the specificity of RedAms for reduction of imines over ketones, and the importance of domain flexibility in bringing the reactive participants together for the reaction. This information is used to propose a mechanism for their action and also to expand the substrate specificity of RedAms using protein engineering.
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