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Issue 19, 2020
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Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases

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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 14 000 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.

Graphical abstract: Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases

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Supplementary files

Article information


Submitted
21 Apr 2020
Accepted
30 Apr 2020
First published
05 May 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 5052-5057
Article type
Edge Article

Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases

J. Mangas-Sanchez, M. Sharma, S. C. Cosgrove, J. I. Ramsden, J. R. Marshall, T. W. Thorpe, R. B. Palmer, G. Grogan and N. J. Turner, Chem. Sci., 2020, 11, 5052
DOI: 10.1039/D0SC02253E

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