“Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli”
Jessica E. Flower, William J Gibbons, Alexandra M. Adams, Xin Wang, Caroline N. Broude, J Andrew Jones
Biotechnology and Bioengineering June 20, 2023 DOI: 10.1002/bit.28480 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Co-cultures Enzyme promiscuity Tryptamine Tryptophan synthase Biosynthesis Psychedelic compounds Metabolic engineering Enzyme engineering Pharmaceutical production |
| Citations | 26 |
| Key findings | Incorporating PsiH into the bacterial psilocybin pathway enables de novo production of psilocybin and 13 derivatives, and the pathway's substrate promiscuity allows biosynthesis of a library of previously unstudied drug candidates. |
Abstract
Abstract Traditional psychedelics are undergoing a transformation from recreational drugs, to promising pharmaceutical drug candidates with the potential to provide an alternative treatment option for individuals struggling with mental illness. Sustainable and economic production methods are thus needed to facilitate enhanced study of these drug candidates to support future clinical efforts. Here, we expand upon current bacterial psilocybin biosynthesis by incorporating the cytochrome P450 monooxygenase, PsiH, to enable the de novo production of psilocybin as well as the biosynthesis of 13 psilocybin derivatives. The substrate promiscuity of the psilocybin biosynthesis pathway was comprehensively probed by using a library of 49 single‐substituted indole derivatives, providing biophysical insights to this understudied metabolic pathway and opening the door to the in vivo biological synthesis of a library of previously unstudied pharmaceutical drug candidates.
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 21
- Methyl transfer in psilocybin biosynthesis Nature Communications March 28, 2024
- Pharmacological and behavioural effects of tryptamines present in psilocybin‐containing mushrooms British Journal of Pharmacology June 2, 2024
- Optimized psilocybin production in tryptophan catabolism‐repressed fungi Microbial Biotechnology November 1, 2024
- De Novo Biosynthesis of Antidepressant Psilocybin in Escherichia coli Microbial Biotechnology April 1, 2025
- Psilocybin biosynthesis enhancement through gene source optimization. Metabolic Engineering April 16, 2025
and 16 more in the library
Cites 20
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Psilocybin-Occasioned Mystical Experiences in the Treatment of Tobacco Addiction Current Drug Abuse Reviews January 9, 2015
- Structure-based discovery of nonhallucinogenic psychedelic analogs Science January 27, 2022
- Potential Therapeutic Effects of Psilocybin. Neurotherapeutics July 1, 2017
and 15 more in the library