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Photoenzymatic Catalysis Enables Radical‐Mediated Ketone Reduction in Ene‐Reductases
Author(s) -
Sandoval Braddock A.,
Kurtoic Sarah I.,
Chung Megan M.,
Biegasiewicz Kyle F.,
Hyster Todd K.
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201902005
Subject(s) - chemistry , ketyl , flavin group , reactivity (psychology) , ketone , biocatalysis , catalysis , hydride , photoredox catalysis , cofactor , substrate (aquarium) , electron transfer , enzyme catalysis , photochemistry , combinatorial chemistry , redox , enzyme , reaction mechanism , benzophenone , organic chemistry , medicine , hydrogen , oceanography , alternative medicine , pathology , photocatalysis , geology
Flavin‐dependent ene‐reductases (EREDs) are known to stereoselectively reduce activated alkenes, but are inactive toward carbonyls. Demonstrated here is that in the presence of photoredox catalysts, these enzymes will reduce aromatic ketones. Mechanistic experiments suggest this reaction proceeds through ketyl radical formation, a reaction pathway that is distinct from the native hydride‐transfer mechanism. Furthermore, this reactivity is accessible without modification of either the enzyme or cofactors, allowing both native and non‐natural mechanisms to occur simultaneously. Based on control experiments, we hypothesize that binding to the enzyme active site attenuates the reduction potential of the substrate, enabling single‐electron reduction. This reactivity highlights opportunities to access new catalytic manifolds by merging photoredox catalysis with biocatalysis.