Biosynthesis of salvinorin A proceeds via the deoxyxylulose phosphate pathway.
Lukasz Kutrzeba, Franck E Dayan, J'Lynn Howell, Ju Feng, José-luis Giner, Jordan K Zjawiony
Phytochemistry July 1, 2007 DOI: 10.1016/j.phytochem.2007.04.034 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Salvia divinorum microshoots |
| Interventions | [Me-(13)C]-methionine and [1-(13)C;3 4-(2)H2]-1-deoxy-D-xylulose |
| Topics | Salvia divinorum |
| Keywords | Salvinorin a biosynthesis Dxp pathway Enzymatic methylation |
| Citations | 45 |
| Key findings | Salvinorin A is biosynthesized via the 1-deoxy-D-xylulose-5-phosphate pathway, and its C-4 carboxyl methylation is catalyzed by a type III S-adenosyl-L-methionine-dependent O-methyltransferase. |
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.
Comparable studies
Other experimental studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. | 2002 | Experimental study | |
| Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Cloned human kappa-opioid receptors expressed in human embryonic kidney-293 cells and... | 2004 | Experimental study | |
| Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues. Animal model | 2014 | Experimental study | |
| Identification of the molecular mechanisms by which the diterpenoid salvinorin A binds to kappa-opioid receptors. | 2005 | Experimental study | |
| Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Rat brain striatum homogenates | 2009 | Laboratory experiment |
Citations in the library
Cited by 15
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- Biosynthesis of the psychotropic plant diterpene salvinorin A: Discovery and characterization of the Salvia divinorum clerodienyl diphosphate synthase The Plant Journal November 19, 2016
- Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. Organic Letters April 3, 2008
- From local to global-fifty years of research on Salvia divinorum. Journal of Ethnopharmacology February 3, 2014
- Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of Opioid Receptor affinity. Tetrahedron December 20, 2008
and 10 more in the library
Cites 8
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin, a new trans-neoclerodane diterpene from Salvia divinorum(Labiatae) Journal of the Chemical Society Perkin Transactions 1 1982
- Ethnopharmacology of ska María Pastora (Salvia divinorum, Epling and Játiva-M.). Journal of Ethnopharmacology May 1, 1983
- Salvinorin A: from natural product to human therapeutics. Molecular interventions October 1, 2006
- Unambiguous NMR spectral assignments of salvinorin A. Magnetic resonance in chemistry : MRC April 1, 2007
and 3 more in the library