Asymmetric Ene-Reduction by F420-Dependent Oxidoreductases B (FDOR-B) from Mycobacterium smegmatis

Suk Woo Kang, James Antoney, David W. Lupton, Robert Speight, Colin Scott, Colin J. Jackson

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Asymmetric reduction by ene-reductases has received considerable attention in recent decades. While several enzyme families possess ene-reductase activity, the Old Yellow Enzyme (OYE) family has received the most scientific and industrial attention. However, there is a limited substrate range and few stereocomplementary pairs of current ene-reductases, necessitating the development of a complementary class. Flavin/deazaflavin oxidoreductases (FDORs) that use the uncommon cofactor F420 have recently gained attention as ene-reductases for use in biocatalysis due to their stereocomplementarity with OYEs. Although the enzymes of the FDOR-As sub-group have been characterized in this context and reported to catalyse ene-reductions enantioselectively, enzymes from the similarly large, but more diverse, FDOR-B sub-group have not been investigated in this context. In this study, we investigated the activity of eight FDOR-B enzymes distributed across this sub-group, evaluating their specific activity, kinetic properties, and stereoselectivity against α,β-unsaturated compounds. The stereochemical outcomes of the FDOR-Bs are compared with enzymes of the FDOR-A sub-group and OYE family. Computational modelling and induced-fit docking are used to rationalize the observed catalytic behaviour and proposed a catalytic mechanism.

Original languageEnglish
Article numbere202200797
JournalChemBioChem
Volume24
Issue number8
DOIs
Publication statusPublished - 17 Apr 2023
Externally publishedYes

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