Biosynthesis of salvinorin A proceeds via the deoxyxylulose phosphate pathway.
Phytochemistry – July 01, 2007
Source: PubMed
Summary
A potent compound from *Salvia divinorum*, Salvinorin A, is now understood to be built through a specific biological pathway. Researchers fed plant microshoots labeled molecules, confirming this pharmacologically important compound is synthesized via the 1-deoxy-D-xylulose-5-phosphate pathway. This discovery clarifies its natural production route. A specific O-methyltransferase enzyme was also identified, catalyzing a crucial methylation step in its formation. This work illuminates the precise natural production of this unique compound.
Abstract
Salvinorin A, a neoclerodane diterpenoid, isolated from the Mexican hallucinogenic plant Salvia divinorum, is a potent kappa-opioid receptor agonist. Its biosynthetic route was studied by NMR and HR-ESI-MS analysis of the products of the incorporation of [1-(13)C]-glucose, [Me-(13)C]-methionine, and [1-(13)C;3,4-(2)H2]-1-deoxy-D-xylulose into its structure. While the use of cuttings and direct-stem injection were unsuccessful, incorporation of (13)C into salvinorin A was achieved using in vitro sterile culture of microshoots. NMR spectroscopic analysis of salvinorin A (2.7 mg) isolated from 200 microshoots grown in the presence of [1-(13)C]-glucose established that this pharmacologically important diterpene is biosynthesized via the 1-deoxy-D-xylulose-5-phosphate pathway, instead of the classic mevalonic acid pathway. This was confirmed further in plants grown in the presence of [1-(13)C;3,4-(2)H2]-1-deoxy-D-xylulose. In addition, analysis of salvinorin A produced by plants grown in the presence of [Me-(13)C]-methionine indicates that methylation of the C-4 carboxyl group is catalyzed by a type III S-adenosyl-L-methionine-dependent O-methyltransferase.