Salvinorin B as a Putative Biosynthetic Precursor of Salvinorin A. Study on O-Acetyltransferasein Glandular Trichomes Isolated from Salviadivinorium

Salvia divinorum is a hallucinogenic mint native to Oaxaca, Mexico. Salvinorin A (1), a diterpenoid isolated from this plant, is a potent and selective κ-opioid agonist, expressing therapeutic potential in treatment of CNS disorders [1]. The biosynthesis of salvinorin A occurs via the non-mevalonate pathway [2] within glandular trichomes located on the abaxial side of the leaves [3]. We now report an optimized method of glands isolation using dry ice leaf abrasion. Acetylation of salvinorin B (2), the putative biosynthetic precursor of salvinorin A, was measured in isolated glandular trichome preparations. Incubation of 18 µM salvinorin B with [¹⁴C]acetyl-CoA (spec. act. 55 mCi/mmol) resulted in the formation of ¹⁴C-labeled salvinorin A. This suggests that glandular trichomes contain a diterpenoid specific O -acetyltransferase which catalyses the acetylation of salvinorin B to form the pharmacologically active product, salvinorin A. The assay was improved through buffer, pH, and temperature optimized conditions. Substrate specificity was measured by testing 2-epi- and 8-epi-salvinorin B stereoisomers as substrates. References: [1] Roth BL, et al. (2002) PNAS 99: 11934–11939. [2] Kutrzeba LM, et al. (2007) Phytochemistry 68: 1872–1881. [3] Siebert D (2004) Ann. Bot. 93: 763–771.