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Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases

DOI: 10.1039/D0SC02253E DOI Help

Authors: Juan Mangas-sanchez (University of Manchester) , Mahima Sharma (University of York) , Sebastian C. Cosgrove (University of Manchester) , Jeremy I. Ramsden (University of Manchester) , James R. Marshall (University of Manchester) , Thomas W. Thorpe (University of Manchester) , Ryan B. Palmer (University of Manchester) , Gideon Grogan (University of York) , Nicholas J. Turner (University of Manchester)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Chemical Science , VOL 11 , PAGES 5052 - 5057

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 9948 , 13587

Open Access Open Access

Abstract: Chiral primary amines are important intermediates in the synthesis of pharmaceutical compounds. Fungal reductive aminases (RedAms) are NADPH-dependent dehydrogenases that catalyse reductive amination of a range of ketones with short-chain primary amines supplied in an equimolar ratio to give corresponding secondary amines. Herein we describe structural and biochemical characterisation as well as synthetic applications of two RedAms from Neosartorya spp. (NfRedAm and NfisRedAm) that display a distinctive activity amongst fungal RedAms, namely a superior ability to use ammonia as the amine partner. Using these enzymes, we demonstrate the synthesis of a broad range of primary amines, with conversions up to >97% and excellent enantiomeric excess. Temperature dependent studies showed that these homologues also possess greater thermal stability compared to other enzymes within this family. Their synthetic applicability is further demonstrated by the production of several primary and secondary amines with turnover numbers (TN) up to 14[thin space (1/6-em)]000 as well as continous flow reactions, obtaining chiral amines such as (R)-2-aminohexane in space time yields up to 8.1 g L−1 h−1. The remarkable features of NfRedAm and NfisRedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis.

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

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength)

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