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Discovery of New Carbonyl Reductases Using Functional Metagenomics and Applications in Biocatalysis

Newgas, Sophie A; Jeffries, Jack WE; Moody, Thomas S; Ward, John M; Hailes, Helen C; (2021) Discovery of New Carbonyl Reductases Using Functional Metagenomics and Applications in Biocatalysis. Advanced Synthesis and Catalysis , 363 (12) pp. 3044-3052. 10.1002/adsc.202100199. Green open access

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Abstract

Enzyme discovery for use in the manufacture of chemicals, requiring high stereoselectivities, continues to be an important avenue of research. Here, a sequence directed metagenomics approach is described to identify short chain carbonyl reductases. PCR from a metagenomic template generated 37 enzymes, with an average 25% sequence identity, twelve of which showed interesting activities in initial screens. Six of the most productive enzymes were then tested against a panel of 21 substrates, including bulkier substrates that have been noted as challenging in biocatalytic reductions. Two enzymes were selected for further studies with the Wieland Miescher ketone. Notably, enzyme SDR-17, when co-expressed with a co-factor recycling system produced the anti-(4aR,5S) isomer in excellent isolated yields of 89% and 99% e.e. These results demonstrate the viability of a sequence directed metagenomics approach for the identification of multiple homologous sequences with low similarity, that can yield highly stereoselective enzymes with applicability in industrial biocatalysis. (Figure presented.).

Type: Article
Title: Discovery of New Carbonyl Reductases Using Functional Metagenomics and Applications in Biocatalysis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/adsc.202100199
Publisher version: https://doi.org/10.1002/adsc.202100199
Language: English
Additional information: © 2021 The Authors. Advanced Synthesis & Catalysis published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/).
Keywords: biocatalysis, carbonyl reductases, short-chain reductases, Wieland-Meischer ketone, functional metagenomics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10127232
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