An international study has found that two types of mushrooms have independently evolved different biochemical pathways for producing psilocybin – the psychoactive substance currently being studied as a treatment for drug-resistant depression.
Scientists have discovered that mushrooms have evolved the ability to produce psilocybin – the psychoactive substance known as “mushroom magic” – not once but twice, and using completely different biochemical toolkits.
This is a rare case of convergent evolution, in which nature arrived at the same mind-altering molecule through two separate pathways. The exact reason why mushrooms produce psilocybin remains a mystery, but hypotheses range from defense against predators to chemical communication between organisms. Beyond evolutionary curiosity, the discovery also provides a new “toolbox” of enzymes that could be used to more efficiently produce psilocybin for medical purposes.
An ancient molecule with a modern role
"This is research into the biosynthesis of a molecule that has a long history with mankind," explained Prof. Dirk Hofmeister, head of the Pharmaceutical Microbiology research group at Friedrich Schiller University Jena and the Leibniz Institute for Natural Products Research and Infection Biology (Leibniz-HKI).
"We are referring to psilocybin, a substance found in so-called 'magic mushrooms,' which our bodies convert into psilocin – a compound that can profoundly alter consciousness. Beyond psychedelic experiences, psilocybin is also considered a promising substance for the treatment of resistant depression," Hofmeister added.
Two evolutionary pathways for psilocybin production
The study, conducted as part of the "Balance of the Microverse" cluster of excellence, revealed that mushrooms developed the ability to produce psilocybin on at least two separate occasions during evolution. Mushrooms of the genus psilocybe use a known enzymatic pathway to produce the molecule, while fungi of the genus inocybe (also known as fiber caps) use a completely different set of enzymes. Although they are different biochemical tools, both groups ultimately produce the same substance.
Two different pathways – one molecule
In other words: two completely different pathways lead to the same goal. Psilocybe and Inocybe mushrooms independently evolved different enzyme pathways that all lead to the production of psilocybin – a rare case of convergent evolution in the field of biosynthesis.
Hidden clues in fungal genomes
Tim Schafer, a doctoral student in Hofmeister's research group and the first author of the paper, explained: "It was like looking at two different workshops, and ultimately getting the same product. In mushrooms of the genus Inocybe we found a unique set of enzymes that has nothing to do with the enzymes of Psilocybe. And yet, they all carry out the steps required to create psilocybin."
The team examined these enzymes in the laboratory. Using protein models built by chemist Bernhard Rupp of the University of Innsbruck, they confirmed that the sequence of reactions in Inocybe is very different from that known in Psilocybe. "Here, nature has essentially invented the same active molecule twice," Schafer emphasized.
An evolutionary puzzle: Why do mushrooms produce psilocybin?
Despite understanding how psilocybin is created, the question why Whether mushrooms produce the molecule is still open. “The simple answer is: we don’t know,” Hofmeister said. “Nature doesn’t do anything without a reason. There must be an advantage to both the Psilocybe mushrooms that live on dung or wood litter and the Inocybe mushrooms that grow in the forest producing this compound—but we don’t know what it is yet.”
One possible hypothesis is that psilocybin is designed to deter predators. Psilocybe mushrooms, for example, turn blue when damaged, the result of a chemical chain that breaks down psilocybin. This chemical reaction may serve as a chemical defense.
Biotechnological potential
Besides the evolutionary aspect, the discovery has practical implications: "Now that we know more enzymes, we have more tools for the biotechnological production of psilocybin," explained Hofmeister.
Schaefer added: “We hope that our results will help in the future to produce psilocybin in industry using bioreactors, without the need for complex chemical syntheses.” At Leibniz-HKI Bina, Hofmeister’s team works closely with the Biological Pilot Unit, which develops processes for the production of natural products such as psilocybin on an industrial scale.
Nature's hidden strategies
The research also provides insight into the diverse chemical pathways used by fungi and the complex relationships between them and their environment. It fits into the central questions of the collaborative research center ChemBioSys and the cluster of excellence "Balance of the Microverse" at Friedrich Schiller University Jena, and is funded by the German Research Foundation (DFG).
מקור:
"Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms”
Tim Schäfer, Fabian Haun, Bernhard Rupp, Dirk Hoffmeister
Angewandte Chemie International Edition, 21.9.2025
