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 journalArticlepeer-review

80 Scopus citations


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
Issue number26
StatePublished - Jun 24 2019
Externally publishedYes


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

ASJC Scopus subject areas

  • Catalysis
  • General Chemistry


Dive into the research topics of 'Photoenzymatic Catalysis Enables Radical-Mediated Ketone Reduction in Ene-Reductases'. Together they form a unique fingerprint.

Cite this