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

Abstract

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 (Cα). The last step, the decomposition of a pyrrolidine species, is rate-limiting with an overall barrier of 18.9 kcal mol-1. Furthermore, when α-hydroxycinnamic acid is used, the Glu282 is found to have another face to transport the hydroxyl proton to the Cβ 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.