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The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines

Cárdenas‐Fernández, Max; Roddan, Rebecca; Carter, Eve M; Hailes, Helen C; Ward, John M; (2023) The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines. ChemCatChem 10.1002/cctc.202201126. (In press). Green open access

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Abstract

Imine reductases (IREDs) are NADPH-dependent enzymes with significant biocatalytic potential for the synthesis of primary, secondary, and tertiary chiral amines. Their applications include the reduction of cyclic imines and the reductive amination of prochiral ketones. In this study, twenty-nine novel IREDs were revealed through genome mining. Imine reductase activities were screened at pH 7 and 9 and in presence of either NADPH or NADH; some IREDs showed good activities at both pHs and were able to accept both cofactors. IREDs with Asn and Glu at the key 187 residue showed preference for NADH. IREDs were also screened against a series of dihydroisoquinolines to synthesise tetrahydroisoquinolines (THIQs), bioactive alkaloids with a wide range of therapeutic properties. Selected IREDs showed high stereoselectivity, as well high THIQ yields (>90 %) when coupled to a glucose-6-phosphate dehydrogenase for NADPH cofactor recycling.

Type: Article
Title: The Discovery of Imine Reductases and their Utilisation for the Synthesis of Tetrahydroisoquinolines
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cctc.202201126
Publisher version: https://doi.org/10.1002/cctc.202201126
Language: English
Additional information: © 2022 The Authors. ChemCatChem published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Imine reductases, reductive amination, activity screening, phylogenetic analysis, tetrahydroisoquinolines
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 Maths and Physical Sciences
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 > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10163413
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