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Mushrooms have evolved psychedelics twice, and scientists have discovered

Psilocybe Cubensis develops in the world in tropical and subtropical regions, notably Central and South America, Southeast Asia and Oceania. The fungus prefers wet floors rich in fertilizers and contains psychoactive psilocybin, which is currently sought as active compound for the treatment of depression resistant to therapy. Credit: Felix Blei, LeibniZhki

Scientists have discovered that fungi have evolved the ability to psilocybin Not once but twice, using completely different biochemical tools.

This rare case of convergent evolution shows nature arriving at the same molecule altering the mind by two distinct paths. The real reason why mushrooms produce psilocybin remains unresolved, but theories range from the defense of predators to chemical communication. Beyond the evolutionary plot, the discovery also offers new enzymatic tools that could help produce psilocybin more effectively for future drugs.

Old molecule with a modern role

“This concerns the biosynthesis of a molecule that has a very long history with humans,” explains Professor Dirk Hoffmeister, head of the pharmaceutical microbiology research group at Friedrich Schiller Jena University and at the Leibniz Institute for the natural research of products and the biology of infections (Leibniz-Hki).

“We refer to psilocybin, a substance found in” magic mushrooms “, which our body converts to psilocin – a compound which can deeply modify consciousness. However, psilocybin triggers not only psychedelic experiences, but is also considered a promising active compound in the treatment of depression resistant to therapy, “says Hoffmeister.

Two scalable paths to psilocybin

The study, carried out in the group of excellence, “the balance of microverses”, reveals that fungi developed the ability to produce psilocybin on at least two distinct occasions from evolutionary history. Psilocybe Mushrooms rely on a familiar enzymes set to make the molecule, while fiber cap mushrooms use a fully different biochemical toolbox. Despite these very different methods, the two groups arrive at the same compound. Scientists call this convergent development, when it is not linked species evolve independently the same trait.

Two different ways of the biosynthesis of the psilocybins
Two ways lead to the same molecule: independently of each other, different kinds of “magic mushrooms” have developed two different enzymatic paths which produce the same psychoactive substance, psilocybin – a rare example of convergent evolution in the biosynthesis of natural products. Credit: Tim Schäfer, LeibniZhki

Hidden indices in fungal genomes

The main author Tim Schäfer, doctoral researcher at the Hoffmeister laboratory, explains: “It was like watching two different workshops, but both ultimately providing the same product. In fiber caps, we have found a unique set of enzymes that have nothing to do with those found in Psilocybe Mushrooms. Nevertheless, they catalyze all the stages necessary to form psilocybin. »»

The team then studied these enzymes in the laboratory. By using protein models built by the chemist innsbruck Bernhard Rupp, they confirmed that the reaction sequence in fiber caps differs considerably from what is known in Psilocybe. “Here, nature has actually invented the same active compound twice,” notes Schäfer.

Mysteries behind the goal of the molecule

However, why two groups of mushrooms in these different produce the same active compound remains uncertain. “The real answer is: we do not know,” says Hoffmeister. “Nature does nothing without reason. There must therefore be an advantage for the two fiber cap mushrooms in the forest and Psilocybe Species of manure or wooden mulch producing this molecule – we simply do not know what it is. »»

“One possible reason could be that psilocybin is intended to dissuade predators. Even the smallest injuries cause Psilocybe The mushrooms are turning blue by a chemical chain reaction, revealing the breakdown products of the psilocybin. Perhaps the molecule is a type of chemical defense mechanism, ”explains Hoffmeister.

Biotechnological opportunities from fungal chemistry

Although it is still not clear why different mushrooms finally produce the same molecule, the discovery nevertheless has practical implications: “Now that we know additional enzymes, we have more tools in our toolbox for the biotechnological production of psilocybin”, explains Hoffmeister.

Schäfer also looks to the future: “We hope that our results will contribute to the future production of psilocybin for pharmaceutical products in bioreactors without the need for complex chemical syntheses.” At Leibniz-Hki in Jena, the Hoffmeister team works in close collaboration with the Bio Pilot factory, which develops natural products production processes, such as psilocybine, on an industrial scale.

Unlock hidden strategies of nature

At the same time, the study provides exciting information on the diversity of chemical strategies used by fungi and their interactions with their environment. He thus addresses the central questions of the Center for Collaborative Research Chemins and the Group of Excellence ׅ ‘Balance of the Microverse’ at the University of Friedrich Schiller Jena, within which the work was carried out and financed by the German Research Foundation (DFG), among others. While the CRC Cheminés studies how natural compounds shape biological communities, the group of excellence focuses on the complex dynamics of microorganisms and their environment.

Reference: “Different reactions and enzymes of the biosynthesis of the psilocybine in Inocybe And Psilocybe Mushrooms ”by Tim Schäfer, Fabian Haun, Bernhard Rupp and Dirk Hoffmeister, September 21, 2025, International edition of applied chemistry.
Two: 10.1002 / Anie.202512017

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