A Mechanism for Reductive Amination Catalyzed by Fungal Reductive Aminases

Mahima Sharma, Juan Mangas-Sanchez, Scott P. France, Godwin A. Aleku, Sarah L. Montgomery, Jeremy I. Ramsden, Nicholas J. Turner, Gideon Grogan

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    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.

    Original languageEnglish
    Pages (from-to)11534-11541
    Number of pages8
    JournalACS Catalysis
    Issue number12
    Early online date26 Oct 2018
    Publication statusPublished - 7 Dec 2018


    • amine
    • imine reductase
    • NADPH
    • oxidoreductase
    • reductive amination

    Research Beacons, Institutes and Platforms

    • Manchester Institute of Biotechnology


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