“This concerns the biosynthesis of a molecule that has a very long history with humans,” explains Prof. Dirk Hoffmeister, head of the Pharmaceutical Microbiology research group at Friedrich Schiller University Jena and the Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI).

“We are referring to psilocybin, a substance found in so-called ‘magic mushrooms’, which our body converts into psilocin – a compound that can profoundly alter consciousness. However, psilocybin not only triggers psychedelic experiences, but is also considered a promising active compound in the treatment of therapy-resistant depression,” adds Hoffmeister.

Two Different Paths to the Same Compound

For the first time, researchers have shown that fungi developed the ability to produce psilocybin independently at least twice. Species of Psilocybe use a known set of enzymes, while fiber cap mushrooms employ a completely distinct biochemical process—yet both arrive at the same molecule.

This discovery highlights an example of convergent evolution, where different species evolve the same trait through unique pathways.

Genome Clues Reveal Different Enzyme Systems

Tim Schäfer, lead author of the study and doctoral researcher in Hoffmeister’s team, illustrates the finding:
“It was like looking at two different workshops, but both ultimately delivering the same product. In the fiber caps, we found a unique set of enzymes that have nothing to do with those found in Psilocybe mushrooms. Nevertheless, they all catalyze the steps necessary to form psilocybin.”

Laboratory analysis and protein modeling by Innsbruck chemist Bernhard Rupp confirmed the biochemical differences. “Here, nature has actually invented the same active compound twice,” says Schäfer.

Why Do Mushrooms Make Psilocybin?

The evolutionary reason remains uncertain. “The real answer is: we don’t know,” stresses Hoffmeister. “Nature does nothing without reason. So there must be an advantage to both fiber cap mushrooms in the forest and Psilocybe species on manure or wood mulch producing this molecule – we just don’t know what it is yet.”

One hypothesis points to a defensive function. “One possible reason could be that psilocybin is intended to deter predators. Even the smallest injuries cause Psilocybe mushrooms to turn blue through a chemical chain reaction, revealing the breakdown products of psilocybin. Perhaps the molecule is a type of chemical defense mechanism,” explains Hoffmeister.

Implications for Biotechnology

Despite the evolutionary mystery, the discovery has clear practical benefits. “Now that we know about additional enzymes, we have more tools in our toolbox for the biotechnological production of psilocybin,” says Hoffmeister.

Schäfer is also optimistic: “We hope that our results will contribute to the future production of psilocybin for pharmaceuticals in bioreactors without the need for complex chemical syntheses.”

At the Leibniz-HKI in Jena, Hoffmeister’s team collaborates with the Bio Pilot Plant, which is developing large-scale processes for producing natural products like psilocybin.

Broader Research Context

The study not only advances biotechnology but also deepens scientific understanding of fungal chemical diversity and ecological strategies. It contributes to major initiatives such as the Collaborative Research Center ChemBioSys and the Cluster of Excellence ‘Balance of the Microverse’, supported by the German Research Foundation (DFG).

Summary of Key Points

• Researchers discovered that psilocybin production evolved independently in two different mushroom groups.
• Psilocybe and fiber cap mushrooms use entirely distinct enzyme systems but create the same compound.
• The reason fungi produce psilocybin remains unclear, though defense mechanisms are a leading theory.
• The finding expands the enzymatic toolkit available for biotechnological psilocybin production.
• The work was carried out at Friedrich Schiller University Jena and Leibniz-HKI, within the DFG-funded Cluster of Excellence ‘Balance of the Microverse’ and CRC ChemBioSys.

Original Publication
Authors: Tim Schäfer, Fabian Haun, Bernhard Rupp and Dirk Hoffmeister.
Journal: Angewandte Chemie International Edition
DOI: 10.1002/anie.202512017
Article Title: Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms
Article Publication Date: 21-Sep-2025
COI Statement: The authors declare no conflict of interest.

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