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Figure 6.
Fig. 6. Structure-based mechanism of P. roqueforti
aristolochene synthase. Models of the enzyme complexed with
substrate, intermediates, and product are shown; salient
mechanistic details are outlined in the text and appear
schematically in Fig. 5. Briefly, farnesyl diphosphate binds in
the unique productive conformation prior to the departure of the
diphosphate leaving group (A). The initial cyclization yields
the germacrene A intermediate through formation of the C-1-C-10
bond (B) (the diphosphate leaving group is not shown for
clarity). Protonation of C-6 by Tyr-92 accompanied by C-2-C-7
bond formation closes the 10-membered ring of germacrene A to
form the bicyclic eudesmane cation intermediate (C). A
1,2-hydride transfer, accompanied by a C-14 methyl migration and
the elimination of H  8, yield
aristolochene (D). Figure prepared with AVS (44).
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