A (-)-kolavenyl diphosphate synthase catalyzes the first step of salvinorin A biosynthesis in Salvia divinorum.
Xiaoyue Chen, Anna Berim, Franck E Dayan, David R Gang
Journal of experimental botany February 1, 2017 DOI: 10.1093/jxb/erw493 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Population | Salvia divinorum peltate glandular trichomes and recombinant diterpene synthase enzymes |
| Topics | Salvia divinorum |
| Keywords | –-kolavenol –-kolavenyl diphosphate Diterpenoid diversification Neo-clerodane diterpenoid Neo-functionalization Product specificity Repeated evolution Salvinorin a biosynthesis |
| Key points | The class II diterpene synthase SdKPS catalyzes formation of (-)-kolavenyl diphosphate, the first committed step in salvinorin A biosynthesis, and a single active-site phenylalanine-to-histidine mutation completely redirects its product to ent-copalyl diphosphate. The authors propose structural elements that mediate the natural neo-clerodane backbone and suggest how SdKPS and related enzymes may have evolved from ent-copalyl diphosphate synthase. |
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.
Comparable studies
Other theoretical and historical papers on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. | 2008 | Theoretical or philosophical paper | |
| The claustrum's proposed role in consciousness is supported by the effect and target localization of Salvia divinorum. | 2014 | Theoretical or philosophical paper | |
| Total Synthesis of (-)-Salvinorin A. | 2016 | Theoretical or philosophical paper | |
| Salvia Divinorum: entrSalvia divinorum: Entre la prohibición y la construcción de su conocimientoe a proibição e a construção do seu saber | 2022 | Theoretical or philosophical paper | |
| Salvia divinorum induces body awareness changes comparable to metamorphic symptoms in the Alice in Wonderland syndrome | 2019 | Theoretical or philosophical paper |
Citations in the library
Cited by 9
- DARK Classics in Chemical Neuroscience: Salvinorin A. ACS Chemical Neuroscience December 2, 2020
- A chromosome level reference genome of Diviner's sage (Salvia divinorum) provides insight into salvinorin A biosynthesis. BMC plant biology October 1, 2024
- Identification of clerodane diterpene modifying cytochrome P450 (CYP728D26) in Salvia divinorum - en route to psychotropic salvinorin A biosynthesis. Physiologia plantarum 2024
- Identification of a novel member of the family Betaflexiviridae from the hallucinogenic plant Salvia divinorum. Acta virologica 2019
- Comparative genome analysis provides a foundation for defining salvinorin A biosynthesis in Salvia divinorum Nature Communications March 23, 2026
and 4 more in the library
Cites 11
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Divinorin A, a psychotropic terpenoid, and divinorin B from the hallucinogenic Mexican mint, Salvia divinorum The Journal of Organic Chemistry November 1, 1984
- Salvinorin C, a new neoclerodane diterpene from a bioactive fraction of the hallucinogenic Mexican mint Salvia divinorum. Organic Letters November 29, 2001
- Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders Frontiers in Pharmacology September 8, 2015
- Total synthesis of the hallucinogenic neoclerodane diterpenoid salvinorin A. Organic Letters April 3, 2008
and 6 more in the library