The St. George's mushroom ( Calocybe gambosa ) is a popular edible mushroom, usually picked in May. Unfortunately, however, it also carries a risk as it can easily be confused with young specimens of the deadly fibrecap, which can lead to potentially fatal poisoning. The reason for this is the mushroom toxin muscarine, which is present in high concentrations in the deadly fibrecap. Muscarine is best known from the fly agaric, in which it was first discovered. In fact, although the fly agaric is the best-known muscarine-containing mushroom, it is not the most dangerous, as it contains comparatively little of this toxin, says Dirk Hoffmeister. He is a professor at Friedrich Schiller University in Jena and is affiliated with the Leibniz-HKI through his research group.
Unexpected results
Another mushroom with a high muscarine content is the fool’s funnel ( Collybia rivulosa ). Sebastian Dörner, the study’s lead author, used this species to test the model of muscarine biosynthesis established in 1977 and found that it was untenable. “Conrad Eugster certainly made the most of the methods and instrumental capabilities available at the time, but measurement techniques in the 1970s were not as precise as they are today,” explains Hoffmeister. Eugster, a chemist and university lecturer at the University of Zurich, to whom the new paper is dedicated, was nonetheless a remarkable pioneer in this field.
“Our hypothesis was to confirm the existing model so that we could build on it and possibly identify additional intermediate products of the biosynthesis,” reports Dörner. “Instead, everything had to be revised,” adds Hoffmeister. The scientists discovered that the basic building block for biosynthesis is not the amino acid glutamine, as Eugster had assumed. This meant that the researchers had to develop a new model. “We initially focused on how biosynthesis begins,” explains Dörner. Two other amino acids were identified – molecules from basic metabolism that also form the building blocks of proteins. According to the new findings, a triple methylation of L-lysine initiates muscarine biosynthesis; later, the amino acid L-alanine is also required.
A better understanding of muscarine biosynthesis could lead to the discovery of further intermediates in the future. It would then be necessary to investigate whether these are also toxic or might have pharmaceutical potential. Knowledge of further toxins would undoubtedly be invaluable for the diagnosis and treatment of mushroom poisoning.
Opportunity and responsibility
Surprisingly, the majority of the scientific literature on muscarine is in German, although English has been firmly established as the language of science for decades. Eugster’s publication, containing the now-corrected misinterpretation of muscarine biosynthesis, also appeared in German. “This means that the number of people who will actually consult such a publication again is quite limited. That was both our opportunity and our responsibility to uncover and correct errors,” remarks Dörner.
However, it is a big step from noticing contradictions in laboratory work to questioning the existing theory, Hoffmeister emphasises. “You have to have the courage to question the literature and trust yourself. If I read about a hypothesis or theory, try to reproduce it and it doesn’t work, I first look for the error in my own work, before I investigate whether there is something wrong with the established knowledge.”
This work was carried out in collaboration with Christian Hertweck and his team at the Leibniz-HKI as part of the ChemBioSys Collaborative Research Centre, which focuses on microbial natural products and their functions. “The close collaboration between the groups involved in the Collaborative Research Centre was particularly rewarding,” emphasised Hoffmeister concluded.
S Dörner, K Rogge, F Trottmann, C Hertweck, D Hoffmeister (2026) A Revised Model for Muscarine Biosynthesis Involving Lysine Trimethylation. Angewandte Chemie International Edition , https://doi.org/10.1002/anie.7581705
Angewandte Chemie International Edition
Experimental study
A Revised Model for Muscarine Biosynthesis Involving Lysine Trimethylation
23-Apr-2026