Ultrafast Dynamics and Catalytic Mechanism of Fatty Acid Photodecarboxylase

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.

Automated summary

By using femtosecond spectroscopy, we have characterized the dynamic evolution of fatty acid photodecarboxylase and identified key steps in its reaction mechanism. These results are crucial for understanding the catalytic cycle of the enzyme and for the design of flavin-based artificial photoenzymes.