Biochemistry, Biophysics and Molecular Biology
Journal or Book Title
Journal of the American Chemical Society
Terpene synthases often catalyze complex cyclization reactions that typically represent the committed step in particular biosynthetic pathways, leading to great interest in their enzymatic mechanisms. We have recently demonstrated that substitution of a specific Ile with Thr was sufficient to “short circuit” the complex cyclization reaction normally catalyzed by ent-kaurene synthases to instead produce ent-pimaradiene. Here we report that the complex cyclization/rearrangement reaction catalyzed by abietadiene synthase can be similarly cut short to produce pimaradienes by an analogous Ser for Ala change, albeit with a slight shift in active site location to accommodate the difference in substrate stereochemistry. This result has mechanistic implications for enzymatic catalysis of abietadiene cyclization, and terpene synthases more broadly. Furthermore, these defined single residue switches may be useful in engineering product outcome in diterpene synthases more generally.
American Chemical Society
Wilderman, P. Ross and Peters, Reuben J., "A Single Residue Switch Converts Abietadiene Synthase into a Pimaradiene Specific Cyclase" (2007). Biochemistry, Biophysics and Molecular Biology Publications. 122.