A "Magic Mushroom" multi-product sesquiterpene synthase.

Schäfer E, Seibold PS, Bartram S, Trottmann F, Hänsch V, Gressler M, Chadeayne A, Hertweck C, O'Connor S, Hoffmeister D (2023) A "Magic Mushroom" multi-product sesquiterpene synthase. ChemBioChem 24(21), e202300511.


Psilocybe "magic mushrooms" are chemically well understood for their psychotropic tryptamines. However, the diversity of their other specialized metabolites, in particular terpenoids, has largely remained an open question. Yet, knowledge on the natural product background is critical to understand if other compounds modulate the psychotropic pharmacological effects. CubA, the single clade II sesquiterpene synthase of P. cubensis, was heterologously produced in Escherichia coli and characterized in vitro, complemented by in vivo product formation assays in Aspergillus niger as heterologous host. Extensive GC-MS analyses proved a function as multi-product synthase and, depending on the reaction conditions, cubebol, β-copaene, δ-cadinene and germacrene D were detected as the major products of CubA. In addition, mature P. cubensis carpophores were analysed chromatographically which led to detection of β-copaene and δ-cadinene. Enzymes closely related to CubA are encoded in the genomes of various Psilocybe species. Therefore, our results provide insight into the metabolic capacity of the entire genus.


Markus Greßler
Veit Hänsch
Christian Hertweck
Dirk Hoffmeister
Eike Schäfer
Paula Seibold
Felix Trottmann


doi: 10.1002/cbic.202300511

PMID: 37614035