Ultrafast Dynamics and Catalytic Mechanism of Fatty Acid Photodecarboxylase

Angew Chem Int Ed Engl. 2022 Dec 12;61(50):e202209180. doi: 10.1002/anie.202209180. Epub 2022 Nov 10.

Abstract

Fatty acid photodecarboxylase is a newly discovered flavin photoenzyme that converts a carboxylic acid into a hydrocarbon and a carbon dioxide molecule through decarboxylation. The enzymatic reactions are poorly understood. In this study, we carefully characterized its dynamic evolution with femtosecond spectroscopy. We observed initial electron transfer from the substrate to the flavin cofactor in 347 ps with a stretched dynamic behavior and subsequently captured the critical carbonyloxy radical. The dominant process following this step was decarboxylation in 5.8 ns to form an alkyl radical and a carbon dioxide molecule. We further identified the absorption bands of two carbonyloxy and alkyl radical intermediates. The overall enzymatic quantum efficiency determined by our obtained timescales is 0.81, consistent with the steady-state value. The results are essential to the elucidation of the enzyme mechanism and catalytic photocycle, providing a molecular basis for potential design of flavin-based artificial photoenzymes.

Keywords: Catalytic Photocycle; Electron Transfer; Flavin Photoenzymes; Hydrocarbon Formation; Photodecarboxylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Carbon Dioxide
  • Catalysis
  • Deoxyribodipyrimidine Photo-Lyase* / chemistry
  • Fatty Acids
  • Flavins / chemistry

Substances

  • Deoxyribodipyrimidine Photo-Lyase
  • Fatty Acids
  • Carbon Dioxide
  • Flavins