title: Biosynthesis of salvinorin A proceeds via the deoxyxylulose phosphate pathway.
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.
authors.affiliation: Department of Pharmacognosy, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kutrzeba
authors.forename: Franck E
authors.initials: FE
authors.lastname: Dayan
authors.forename: J'Lynn
authors.initials: J
authors.lastname: Howell
authors.forename: Ju
authors.initials: J
authors.lastname: Feng
authors.forename: José-Luis
authors.initials: JL
authors.lastname: Giner
authors.forename: Jordan K
authors.initials: JK
authors.lastname: Zjawiony
mesh_terms: D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism*; D045785:Diterpenes, Clerodane; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008715:Methionine / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D027544:Salvia / Q000737:chemistry / Q000378:metabolism; D014994:Xylose / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D014996:Xylulose / Q000378:metabolism
chemical_list: D004224:Diterpenes; D045785:Diterpenes, Clerodane; C492551:deoxyxylulose phosphate; D014996:Xylulose; D014994:Xylose; D008715:Methionine; D005947:Glucose; C090499:salvinorin A