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Updated: May 16, 2026

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products
Published on: October 4, 2019
A single residue change leads to a hydroxylated product from the class II diterpene cyclization catalyzed by
Jared Criswell1, Kevin Potter, Freya Shephard
1Department of Biochemistry, Biophysics, & Molecular Biology, Iowa State University, Ames, Iowa 50011, USA.
Abstract:
Class II diterpene cyclases catalyze bicyclization of geranylgeranyl diphosphate. While this reaction typically is terminated via methyl deprotonation to yield copalyl diphosphate, in rare cases hydroxylated bicycles are produced instead. Abietadiene synthase is a bifunctional diterpene cyclase that usually produces a copalyl diphosphate intermediate. Here it is shown that substitution of aspartate for a conserved histidine in the class II active site of abietadiene synthase leads to selective production of 8α-hydroxy-CPP instead, demonstrating striking plasticity.
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