Metagenomic ene-reductases for the bioreduction of sterically challenging enones

Ene-reductases (ERs) of the Old Yellow Enzyme family catalyse asymmetric reduction of activated alkenes providing chiral products. They have become an important method in the synthetic chemists' toolbox offering a sustainable alternative to metal-catalysed asymmetric reduction. Development of n...

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Bibliographic Details
Published in:RSC advances 2019-11, Vol.9 (63), p.3668-36614
Main Authors: Dobrijevic, Dragana, Benhamou, Laure, Aliev, Abil E, Méndez-Sánchez, Daniel, Dawson, Natalie, Baud, Damien, Tappertzhofen, Nadine, Moody, Thomas S, Orengo, Christine A, Hailes, Helen C, Ward, John M
Format: Article
Language:English
Subjects:
Alkenes
Asymmetry
Biotransformation
Chemical Sciences
Chemistry
Chemists
Enzymes
Molecular docking
Organic chemistry
Reductases
Reduction
Reduction (metal working)
Stereoselectivity
Substrates
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Summary:Ene-reductases (ERs) of the Old Yellow Enzyme family catalyse asymmetric reduction of activated alkenes providing chiral products. They have become an important method in the synthetic chemists' toolbox offering a sustainable alternative to metal-catalysed asymmetric reduction. Development of new biocatalytic alkene reduction routes, however needs easy access to novel biocatalysts. A sequence-based functional metagenomic approach was used to identify novel ERs from a drain metagenome. From the ten putative ER enzymes initially identified, eight exhibited activities towards widely accepted mono-cyclic substrates with several of the ERs giving high reaction yields and stereoselectivities. Two highly performing enzymes that displayed excellent co-solvent tolerance were used for the stereoselective reduction of sterically challenging bicyclic enones where the reactions proceeded in high yields, which is unprecedented to date with wild-type ERs. On a preparative enzymatic scale, reductions of Hajos-Parish, Wieland-Miescher derivatives and a tricyclic ketone proceeded with good to excellent yields. Exceptional organic solvent tolerant ene-reductases mined from a drain metagenome library are highly versatile catalysts for difficult enones.
ISSN:2046-2069
2046-2069
DOI:10.1039/c9ra06088j