The Decarboxylation of α,β-Unsaturated Acid Catalyzed by Prenylated FMN-Dependent Ferulic Acid Decarboxylase and the Enzyme Inhibition.

Ferulic acid decarboxylase (Fdc1) is able to catalyze the decarboxylation of α,β-unsaturated acids using a novel cofactor, prenylated flavin mononucleotide (PrFMN). Using density functional theory calculations, we here have investigated the Fdc1 reaction mechanism with the substrate of α-methylcinnamic acid. It is demonstrated that Fdc1 employs a 1,3-dipolar cycloaddition mechanism involving four concerted steps, where the Glu282 acts as a crucial proton donor to protonate the α carbon (C). The last step, the decomposition of a pyrrolidine species, is rate-limiting with an overall barrier of 18.9 kcal mol. Furthermore, when α-hydroxycinnamic acid is used, the Glu282 is found to have another face to transport the hydroxyl proton to the C atom to promote the tautomerization from enol intermediate to ketone species leading to the inhibition of the Fdc1 enzyme. The PrFMN roles are also discussed in detail.