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.