Psilocybin Production With Genetically Modified Aspergillus nidulans Under Pressurized Conditions
Sophie Weiser, Sidney Jung, Bettina Bardl, Johann E. Kufs, Slavica Janevska, Vito Valiante, Dirk Hoffmeister, Lars Regestein
Biotechnology and Bioengineering December 30, 2025 DOI: 10.1002/bit.70137 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Genetically modified Aspergillus nidulans strain |
| Intervention | pressurized bioprocess |
| Duration | 68 hours |
| Topics | Psilocybin |
| Keywords | Bioprocess Tryptamine Biochemical engineering Bioreactor Overproduction Biotechnology Oxygen Fermentation Chromatography Genetically modified organism |
| Citations | 1 |
| Key findings | A batch bioprocess using an overproduction strain of Aspergillus nidulans produced 542 mg L−1 psilocybin within 68 hours from glucose. |
Abstract
ABSTRACT Psilocybin, an indole alkaloid of psychedelic mushrooms, has the potential to sustainably improve the treatment of several psychiatric diseases. So far, the psilocybin demand for clinical trials has been met by chemical synthesis. In this study, we pursued the biotechnological approach to develop a psilocybin production process utilizing an overproduction strain of Aspergillus nidulans . The developed shake flask cultivation regime was characterized rheologically and was evaluated concerning the sensitivity to changes in oxygen availability and power input. Due to the strong impact of power input on viscosity and thus, (oxygen) mass transfer and mixing of the filamentous culture broth, the bioprocess was scaled up from shake flask to 7 L stirred tank reactor according to the specific power input. Utilizing a pressure reactor, the oxygen supply of the viscous culture broth was enhanced. Subsequently, the nitrogen limitation was addressed by supplementing the cultivation medium with additional ammonium sulfate to provide sufficient building blocks for protein biosynthesis. By producing 542 mg L −1 psilocybin within 68 h from glucose, a robust and efficient batch bioprocess for psilocybin production was developed to potentially contribute to the future supply of psilocybin for pharmaceutical purposes. Moreover, we demonstrated the suitability of pressurized bioprocesses to counteract oxygen limitations for shear‐sensitive, filamentous organisms.
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
Cites 19
- Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action Neuroreport December 1, 1998
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- Enzymatic Synthesis of Psilocybin Angewandte Chemie International Edition August 1, 2017
- 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
and 14 more in the library