Elucidation of the mescaline biosynthetic pathway in peyote (Lophophora williamsii).
Jacinta L Watkins, Qiushi Li, Sam Yeaman, Peter J. Facchini
The Plant Journal November 1, 2023 DOI: 10.1111/tpj.16447 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Mescaline |
| Keywords | Lophophora williamsii Alkaloid biosynthesis Isoquinoline Phenethylamine Psychedelics |
| Citations | 23 |
| Key findings | A near-complete biosynthetic pathway from l-tyrosine to mescaline in peyote was elucidated using transcriptomics and homology-guided gene discovery, including identification of a cytochrome P450, a decarboxylase, and four regiospecific O-methyltransferases. |
Abstract
Peyote (Lophophora williamsii) is an entheogenic and medicinal cactus native to the Chihuahuan desert. The psychoactive and hallucinogenic properties of peyote are principally attributed to the phenethylamine derivative mescaline. Despite the isolation of mescaline from peyote over 120 years ago, the biosynthetic pathway in the plant has remained undiscovered. Here, we use a transcriptomics and homology-guided gene discovery strategy to elucidate a near-complete biosynthetic pathway from l-tyrosine to mescaline. We identified a cytochrome P450 that catalyzes the 3-hydroxylation of l-tyrosine to l-DOPA, a tyrosine/DOPA decarboxylase yielding dopamine, and four substrate-specific and regiospecific substituted phenethylamine O-methyltransferases. Biochemical assays with recombinant enzymes or functional analyses performed by feeding putative precursors to engineered yeast (Saccharomyces cerevisiae) strains expressing candidate peyote biosynthetic genes were used to determine substrate specificity, which served as the basis for pathway elucidation. Additionally, an N-methyltransferase displaying broad substrate specificity and leading to the production of N-methylated phenethylamine derivatives was identified, which could also function as an early step in the biosynthesis of tetrahydroisoquinoline alkaloids in peyote.
Comparable studies
Other experimental studies on mescaline, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Enzymatic Formation of Psychotomimetic Metabolites from Normally Occurring Compounds Rabbit lung | 1961 | Experimental study | |
| PSYCHOTOMIMETICS, CLINICAL AND THEORETICAL CONSIDERATIONS: HARMINE, WIN-2299 AND NALLINE Schizophrenic patients | 1957 | Experimental study | |
| Phencyclidine, Lysergic Acid Diethylamide, and Mescaline: Cerebral Artery Spasms and Hallucinogenic Activity Isolated basilar and middle cerebral arteries | 1981 | Experimental study | |
| Acquired and Crossed Tolerance to Mescaline, LSD-25, and BOL-148 | 1959 | Experimental study | |
| Effects of Hallucinogenic and Tranquilizing Drugs on Serotonin Evoked Uterine Contractions. Uterus of spayed rat | 1956 | Experimental study |
Citations in the library
Cited by 10
- The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction Molecular Plant June 3, 2024
- New perspective on sustained antidepressant effect: focus on neurexins regulating synaptic plasticity Cell Death Discovery May 1, 2024
- New frontiers in the biosynthesis of psychoactive specialized metabolites Current Opinion in Plant Biology September 16, 2024
- Bioproduction of 3,4-methylenedioxymethamphetamine and derivatives. Biodesign research June 1, 2025
- Pathway engineering for the biosynthesis of psychedelics Current Opinion in Biotechnology May 15, 2025
and 5 more in the library
Cites 9
- Psychedelic Drugs in Biomedicine TIPS - Trends in Pharmacological Sciences September 22, 2017
- Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions Current Molecular Pharmacology October 15, 2018
- Dark Classics in Chemical Neuroscience: Mescaline ACS Chemical Neuroscience May 30, 2018
- New mescaline concentrations from 14 taxa/cultivars of Echinopsis spp. (Cactaceae) (“San Pedro”) and their relevance to shamanic practice Journal of Ethnopharmacology July 15, 2010
- De novo sequencing and analysis of Lophophora williamsii transcriptome, and searching for putative genes involved in mescaline biosynthesis BMC Genomics September 1, 2015
and 4 more in the library