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A mechanism for reductive amination catalyzed by fungal reductive aminases (RedAms)

DOI: 10.1021/acscatal.8b03491 DOI Help

Authors: Mahima Sharma (University of York) , Juan Mangas-Sanchez (University of Manchester) , Scott P. France (University of Manchester) , Godwin A. Aleku (University of Manchester) , Sarah L. Montgomery (University of Manchester) , Jeremy I. Ramsden (University of Manchester) , Nicholas J. Turner (University of Manchester) , Gideon Grogan (University of York)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Catalysis

State: Published (Approved)
Published: October 2018
Diamond Proposal Number(s): 9948

Abstract: 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.

Journal Keywords: Oxidoreductase; Amine; Imine Reductase; Reductive Amination; NADPH

Diamond Keywords: Enzymes

Subject Areas: Chemistry, Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography

Added On: 29/10/2018 10:17

Discipline Tags:

Catalysis Life Sciences & Biotech Structural biology Chemistry Biochemistry

Technical Tags:

Diffraction Macromolecular Crystallography (MX)