Enzymatic Route toward 6‐Methylated Baeocystin and Psilocybin
Janis Fricke, Alexander M. Sherwood, Robert B. Kargbo, Andrew Orry, Felix Blei, Andreas Naschberger, Bernhard Rupp, Dirk Hoffmeister
ChemBioChem May 31, 2019 DOI: 10.1002/cbic.201900358 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study with in silico modeling Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Enzyme Indole test Methylation In silico Biochemistry Stereochemistry Pharmacology Hallucinogen Alkaloids |
| Citations | 38 |
| Key findings | A biocatalytic route using Psilocybe cubensis enzymes PsiD, PsiK, and PsiM successfully synthesized 6-methylated psilocybin and baeocystin, with an in silico model of PsiM identifying conserved and variable structural elements influencing substrate specificity. |
Abstract
Abstract Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently being investigated in advanced clinical trials. Here, we report a biocatalytic route to synthesize 6‐methylated psilocybin and baeocystin from 4‐hydroxy‐6‐methyl‐ l ‐tryptophan, which was decarboxylated and phosphorylated by the Psilocybe cubensis biosynthesis enzymes PsiD and PsiK. N‐Methylation was catalyzed by PsiM. We further present an in silico structural model of PsiM that revealed a well‐conserved SAM‐binding core along with peripheral nonconserved elements that likely govern substrate preferences.
Comparable studies
Other experimental studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Healthy human volunteers | 1998 | Experimental study | |
| Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Participants in controlled laboratory experiments receiving a moderate to high oral... | 2015 | Validation study using pooled data from five laboratory experiments | n = 184 |
| Broadband Cortical Desynchronization Underlies the Human Psychedelic State Healthy human participants | 2013 | Experimental study | |
| Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer Participants with cancer-related psychiatric distress who completed a parent randomized... | 2020 | Long-term within-subjects follow-up analysis | n = 15 |
| Enzymatic Synthesis of Psilocybin | 2017 | Laboratory study |
Citations in the library
Cited by 24
- Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development. Fungal biology April 1, 2022
- Scalable Hybrid Synthetic/Biocatalytic Route to Psilocybin Chemistry - A European Journal February 26, 2020
- Taking Different Roads: l‐Tryptophan as the Origin of Psilocybe Natural Products ChemPlusChem October 1, 2020
- S‐Adenosyl‐l‐Methionine Salvage Impacts Psilocybin Formation in “Magic” Mushrooms ChemBioChem December 4, 2019
- “Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli” Biotechnology and Bioengineering June 20, 2023
and 19 more in the library
Cites 19
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Pilot study of the 5-HT2AR agonist psilocybin in the treatment of tobacco addiction Journal of Psychopharmacology September 11, 2014
- Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Psychopharmacology March 1, 2004
- Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen Helvetica Chimica Acta 1959
- Enzymatic Synthesis of Psilocybin Angewandte Chemie International Edition August 1, 2017
and 14 more in the library