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Bifunctional Abietadiene Synthase: Mutual Structural Dependence Of The Active Sites For Protonation-Initiated And Ionization-Initiated Cyclizations, Reuben J. Peters, Ora A. Carter, Yan Zhang, Brian W. Matthews, Rodney B. Croteau

Reuben J. Peters

Abietadiene synthase from grand fir catalyzes two sequential, mechanistically distinct cyclizations, of geranylgeranyl diphosphate and of copalyl diphosphate, in the formation of a mixture of abietadiene isomers as the committed step of diterpenoid resin acid biosynthesis. Each reaction is independently conducted at a separate active site residing in what were considered to be structurally distinct domains typical of terpene cyclases. Despite the presence of an unusual 250-residue N-terminal insertional element, a tandem pair of charged residues distal to the insertion was shown to form a functional part of the C-terminal active site. Because abietadiene synthase resembles the ancestral plant terpene …