Biosynthesis of the psychotropic plant diterpene salvinorin A: Discovery and characterization of the Salvia divinorum clerodienyl diphosphate synthase
The Plant Journal November 19, 2016 Kyle A. Pelot, Rod Mitchell, Moonhyuk Kwon et al. 76 citations
Salvia divinorum (diviner's sage) produces clerodane-type diterpenoids, including the bioactive salvinorin A, the first non-nitrogenous natural compound that acts as an opioid-receptor agonist. Two diterpene synthases were discovered and characterized: SdCPS1, an ent-copalyl diphosphate synthase, and SdCPS2, a clerodienyl diphosphate synthase. SdCPS2 catalyzes the committed step in salvinorin A biosynthesis, supported by its trichome-specific expression and the absence of other class II diTPSs. Structure-guided mutagenesis identified four catalytic residues that allowed reprogramming SdCPS2 to produce four distinct products, advancing understanding of neo-functionalization in plant diterpene synthases and offering potential for synthetic biology platforms.