Photoenzymatic Catalysis Enables Radical-Mediated Ketone Reduction in Ene-Reductases

Braddock A. Sandoval, Sarah I. Kurtoic, Megan M. Chung, Kyle F. Biegasiewicz, Todd K. Hyster

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)8714-8718
Number of pages5
JournalAngewandte Chemie - International Edition
Volume58
Issue number26
DOIs
StatePublished - Jun 24 2019

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)

Keywords

  • biocatalysis
  • enzymes
  • hydrogen atom transfer
  • photochemistry
  • reduction

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