In vivo production of psilocybin in E. coli
Alexandra M. Adams, Nicholas A. Kaplan, Zhangyue Wei, John D. Brinton, Chantal Monnier, Alexis L. Enacopol, Theresa A. Ramelot, J. Andrew Jones
Metabolic Engineering September 21, 2019 DOI: 10.1016/j.ymben.2019.09.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Escherichia coli |
| Topics | Psilocybin |
| Keywords | Bioproduction Recombinant dna Escherichia coli Biochemistry Pharmacology |
| Citations | 83 |
| Key findings | A fed-batch fermentation study achieved a psilocybin titer of 1.16 g/L, the highest from a recombinant organism. |
Abstract
Psilocybin, the prodrug of the psychoactive molecule psilocin, has demonstrated promising results in clinical trials for the treatment of addiction, depression, and post-traumatic stress disorder. The development of a psilocybin production platform in a highly engineerable microbe could lead to rapid advances towards the bioproduction of psilocybin for use in ongoing clinical trials. Here, we present the development of a modular biosynthetic production platform in the model microbe, Escherichia coli. Efforts to optimize and improve pathway performance using multiple genetic optimization techniques were evaluated, resulting in a 32-fold improvement in psilocybin titer. Further enhancements to this genetically superior strain were achieved through fermentation optimization, ultimately resulting in a fed-batch fermentation study, with a production titer of 1.16 g/L of psilocybin. This is the highest psilocybin titer achieved to date from a recombinant organism and a significant step towards demonstrating the feasibility of industrial production of biologically-derived psilocybin.
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 54
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- The Therapeutic Potential of Psilocybin Molecules May 15, 2021
- Psilocybin: from ancient magic to modern medicine The Journal of Antibiotics May 12, 2020
- Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives Metabolic Engineering March 26, 2020
- Diversity, biology, and history of psilocybin-containing fungi: Suggestions for research and technological development. Fungal biology April 1, 2022
and 49 more in the library
Cites 15
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer Archives of General Psychiatry September 7, 2010
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- The pharmacology of psilocybin Addiction Biology October 1, 2002
and 10 more in the library