Journal Article

A (–)-kolavenyl diphosphate synthase catalyzes the first step of salvinorin A biosynthesis in Salvia divinorum

Xiaoyue Chen, Anna Berim, Franck E. Dayan and David R. Gang

in Journal Of Experimental Botany

Volume 68, issue 5, pages 1109-1122
Published in print February 2017 | ISSN: 0022-0957
Published online February 2017 | e-ISSN: 1460-2431 | DOI: https://dx.doi.org/10.1093/jxb/erw493
A (–)-kolavenyl diphosphate synthase catalyzes the first step of salvinorin A biosynthesis in Salvia divinorum

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Abstract

Salvia divinorum (Lamiaceae) is an annual herb used by indigenous cultures of Mexico for medicinal and ritual purposes. The biosynthesis of salvinorin A, its major bioactive neo-clerodane diterpenoid, remains virtually unknown. This investigation aimed to identify the enzyme that catalyzes the first reaction of salvinorin A biosynthesis, the formation of (–)-kolavenyl diphosphate [(–)-KPP], which is subsequently dephosphorylated to afford (–)-kolavenol. Peltate glandular trichomes were identified as the major and perhaps exclusive site of salvinorin accumulation in S. divinorum. The trichome-specific transcriptome was used to identify candidate diterpene synthases (diTPSs). In vitro and in planta characterization of a class II diTPS designated as SdKPS confirmed its activity as (–)-KPP synthase and its involvement in salvinorin A biosynthesis. Mutation of a phenylalanine into histidine in the active site of SdKPS completely converts the product from (–)-KPP into ent-copalyl diphosphate. Structural elements were identified that mediate the natural formation of the neo-clerodane backbone by this enzyme and suggest how SdKPS and other diTPSs may have evolved from ent-copalyl diphosphate synthase.

Keywords: class II diterpene synthase; diterpenoid diversification; (–)-kolavenyl diphosphate; (–)-kolavenol; neo-functionalization; neo-clerodane diterpenoid; product specificity; repeated evolution; Salvia divinorum; salvinorin A biosynthesis

Journal Article.  9294 words.  Illustrated.

Subjects: Plant Sciences and Forestry

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