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Identification and characterization of diterpene synthases in the salvinorin A biosynthetic pathway

Rod Mitchell

Libraries and Cultural Resources 2012 DOI: 10.11575/prism/26417 (opens in new tab)

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AI-extracted from the abstract
Characteristics Theoretical or philosophical paper Peer reviewed
Topics Salvia divinorum
Key points The authors report identifying five putative diterpene synthase cDNAs from a Salvia divinorum transcript database and characterize two recombinant enzymes: a type II synthase that converts GGPP to terpentedienyl diphosphate and a type I synthase that converts terpentedienyl diphosphate to kolavenol. They propose these products as potential intermediates in the salvinorin A biosynthetic pathway.

Abstract

Salvia divinorum is a hallucinogenic plant that is used for divination and spiritual communion by the Mazatecs of Mexico. The active component of the plant is salvinorin A, a neoclerodane diterpenoid that selectively acts as a potent κ opioid receptor agonist. Salvinorin A's novel receptor binding profile makes derivatives of the compound potentially useful in the treatment of various psychiatric and mood disorders. In this work, next generation sequencing (Roche 454) was used to generate a S. divinorum transcript database. Five distinct putative diterpene synthase cDNAs (two type II and three type I) were identified in the database. We report here a recombinant type II diterpene synthase capable of catalyzing the rearrangement of GGPP into terpentedienyl diphosphate (a neoclerodane diphosphate), and a recombinant type I diterpene synthase that renders terpentedienyl diphosphate into kolavenol. These enzymatic products are potential intermediates in the salvinorin A biosynthetic pathway.

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