Mechanism and Dynamics of Photodecarboxylation Catalyzed by Lactate Monooxygenase

Xiankun Li, Claire G. Page, Laura Zanetti-Polzi, Aarat P. Kalra, Daniel G. Oblinsky, Isabella Daidone, Todd K. Hyster, Gregory D. Scholes

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Photoenzymes are a rare class of biocatalysts that use light to facilitate chemical reactions. Many of these catalysts utilize a flavin cofactor to absorb light, suggesting that other flavoproteins might have latent photochemical functions. Lactate monooxygenase is a flavin-dependent oxidoreductase previously reported to mediate the photodecarboxylation of carboxylates to afford alkylated flavin adducts. While this reaction holds a potential synthetic value, the mechanism and synthetic utility of this process are unknown. Here, we combine femtosecond spectroscopy, site-directed mutagenesis, and a hybrid quantum-classical computational approach to reveal the active site photochemistry and the role the active site amino acid residues play in facilitating this decarboxylation. Light-induced electron transfer from histidine to flavin was revealed, which has not been reported in other proteins. These mechanistic insights enable the development of catalytic oxidative photodecarboxylation of mandelic acid to produce benzaldehyde, a previously unknown reaction for photoenzymes. Our findings suggest that a much wider range of enzymes have the potential for photoenzymatic catalysis than has been realized to date.

Original languageEnglish (US)
Pages (from-to)13232-13240
Number of pages9
JournalJournal of the American Chemical Society
Issue number24
StatePublished - Jun 21 2023

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • Biochemistry
  • Catalysis
  • Colloid and Surface Chemistry


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