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Instruments / Technical Area	Publication Details	Published	Actions
I03-Macromolecular Crystallography I04-1-Macromolecular Crystallography (fixed wavelength)	Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases Juan Mangas-Sanchez , Mahima Sharma , Sebastian C. Cosgrove , Jeremy I. Ramsden , James R. Marshall , Thomas W. Thorpe , Ryan B. Palmer , Gideon Grogan , Nicholas J. Turner Chemical Science 11, 5052 - 5057 DOI: 10.1039/D0SC02253E Diamond Proposal Number(s): [9948, 13587] Open Access Show Abstract ▼ 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.	May 2020

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I03-Macromolecular Crystallography
I04-1-Macromolecular Crystallography (fixed wavelength)

Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases

Juan Mangas-Sanchez , Mahima Sharma , Sebastian C. Cosgrove , Jeremy I. Ramsden , James R. Marshall , Thomas W. Thorpe , Ryan B. Palmer , Gideon Grogan , Nicholas J. Turner

Chemical Science 11, 5052 - 5057

DOI: 10.1039/D0SC02253E

Diamond Proposal Number(s): [9948, 13587]