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

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