Scalable Hybrid Synthetic/Biocatalytic Route to Psilocybin
Janis Fricke, Robert B. Kargbo, Lars Regestein, Claudius Lenz, Gundela Peschel, Miriam A. Rosenbaum, Alexander M. Sherwood, Dirk Hoffmeister
Chemistry - A European Journal February 26, 2020 DOI: 10.1002/chem.202000134 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Tryptamine Combinatorial chemistry Pharmacology Biochemistry Hallucinogen Alkaloids |
| Citations | 48 |
| Key findings | The mushroom enzyme PsiK can replace a problematic chemical phosphorylation step to produce one gram of psilocybin from psilocin in 20 minutes. |
Abstract
Abstract Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment‐resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis with the mushroom kinase PsiK. This enzyme was biochemically characterized and used to produce one gram of psilocybin from psilocin within 20 minutes. We also describe a pilot‐scale protocol for recombinant PsiK that yielded 150 mg enzyme in active and soluble form. Our work consolidates the simplicity of tryptamine chemistry with the specificity and selectivity of enzymatic catalysis and helps provide access to an important drug at potentially reasonable cost.
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 37
- The Therapeutic Potential of Psilocybin Molecules May 15, 2021
- Psilocybin: from ancient magic to modern medicine The Journal of Antibiotics May 12, 2020
- Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development. Fungal biology April 1, 2022
- Genetic Survey of Psilocybe Natural Products ChemBioChem May 18, 2022
- Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents Biomedicines February 5, 2023
and 32 more in the library
Cites 16
- Potential Therapeutic Effects of Psilocybin. Neurotherapeutics July 1, 2017
- Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen Helvetica Chimica Acta 1959
- Enzymatic Synthesis of Psilocybin Angewandte Chemie International Edition August 1, 2017
- DARK Classics in Chemical Neuroscience: Psilocybin ACS Chemical Neuroscience June 29, 2018
- Horizontal gene cluster transfer increased hallucinogenic mushroom diversity Evolution Letters February 27, 2018
and 11 more in the library