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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
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 …
Mechanism Of Abietadiene Synthase Catalysis: Stereochemistry And Stabilization Of The Cryptic Pimarenyl Carbocation Intermediates, Reuben J. Peters, Matthew M. Ravn, Robert M. Coates, Rodney Croteau
Mechanism Of Abietadiene Synthase Catalysis: Stereochemistry And Stabilization Of The Cryptic Pimarenyl Carbocation Intermediates, Reuben J. Peters, Matthew M. Ravn, Robert M. Coates, Rodney Croteau
Reuben J. Peters
Abietadiene synthase (AS) catalyzes the complex cyclization-rearrangement of (E,E,E)-geranylgeranyl diphosphate (8, GGPP) to a mixture of abietadiene (1a), double bond isomers 2a-4a and pimaradienes 5a-7a as a key step in the biosynthesis of the abietane resin acid constituents (1b-4b) of conifer oleoresin. The reaction proceeds at two active sites by way of the intermediate, copalyl diphosphate (9). In the second site, a putative tricyclic pimaradiene or pimarenyl(+) carbocation intermediate of undefined C13 stereochemistry and annular double bond position is formed. Three 8-oxy-17-nor analogues of 9 (17 and 19a,b) and three isomeric 15,16-bisnorpimarenyl-N-methylamines (26a-c) were synthesized and evaluated as alternative substrates …