Mechanism and dynamics of fatty acid photodecarboxylase

Fatty acid photodecarboxylase (FAP) is a photoenzyme with potential green chemistry applications. By combining static, time-resolved, and cryotrapping spectroscopy and crystallography as well as computation, we characterized Chlorella variabilis FAP reaction intermediates on time scales from subpicoseconds to milliseconds. High-resolution crystal structures from synchrotron and free electron laser x-ray sources highlighted an unusual bent shape of the oxidized flavin chromophore. We demonstrate that decarboxylation occurs directly upon reduction of the excited flavin by the fatty acid substrate. Along with flavin reoxidation by the alkyl radical intermediate, a major fraction of the cleaved carbon dioxide unexpectedly transformed in 100 nanoseconds, most likely into bicarbonate. This reaction is orders of magnitude faster than in solution. Two strictly conserved residues, R451 and C432, are essential for substrate stabilization and functional charge transfer.

Automated summary

The study found that Fatty Acid Photodecarboxylase (FAP) exhibits efficient decarboxylation activity, primarily achieved through the reduction of the flavin chromophore and direct removal of carbon dioxide by the substrate carboxyl group. Essential residues R451 and C432 are crucial for substrate stabilization and charge transfer.