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A reductive aminase from Aspergillus oryzae

DOI: 10.1038/nchem.2782 DOI Help

Authors: Godwin A. Aleku (Manchester Institute of Biotechnology) , Scott P. France (Manchester Institute of Biotechnology) , Henry Man (University of York) , Juan Mangas-Sanchez (Manchester Institute of Biotechnology) , Sarah L. Montgomery (Manchester Institute of Biotechnology) , Mahima Sharma (University of York) , Friedemann Leipold (Manchester Institute of Biotechnology) , Shahed Hussain (Manchester Institute of Biotechnology) , Gideon Grogan (University of York) , Nicholas J. Turner (Manchester Institute of Biotechnology)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Chemistry , VOL 94

State: Published (Approved)
Published: May 2017
Diamond Proposal Number(s): 9948

Abstract: Reductive amination is one of the most important methods for the synthesis of chiral amines. Here we report the discovery of an NADP(H)-dependent reductive aminase from Aspergillus oryzae (AspRedAm, Uniprot code Q2TW47) that can catalyse the reductive coupling of a broad set of carbonyl compounds with a variety of primary and secondary amines with up to >98% conversion and with up to >98% enantiomeric excess. In cases where both carbonyl and amine show high reactivity, it is possible to employ a 1:1 ratio of the substrates, forming amine products with up to 94% conversion. Steady-state kinetic studies establish that the enzyme is capable of catalysing imine formation as well as reduction. Crystal structures of AspRedAm in complex with NADP(H) and also with both NADP(H) and the pharmaceutical ingredient (R)-rasagiline are reported. We also demonstrate preparative scale reductive aminations with wild-type and Q240A variant biocatalysts displaying total turnover numbers of up to 32,000 and space time yields up to 3.73 g l−1 d−1.

Journal Keywords: Biocatalysis

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography

Added On: 06/06/2017 08:57

Discipline Tags:

Health & Wellbeing Biochemistry Catalysis Chemistry Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)