Specific and Multi‐Product Clade I and Clade IV Sesquiterpene Synthases Contribute to the Psilocybe cubensis Volatilome
Sebastian Schober, Lisa Dorfmann, Karl Walther, Felix Blei, Andrew R Chadeayne, Markus Gressler, Stefan Bartram, Sarah E. O’connor, Dirk Hoffmeister
ChemBioChem April 1, 2026 DOI: 10.1002/cbic.70318 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Qualitative Peer reviewed |
|---|---|
| Population | Psilocybe cubensis enzymes and Aspergillus niger host; P. cubensis mycelium and fruiting bodies |
| Keywords | Sesquiterpene Clade Mycelium Secondary metabolite Terpenoid Aspergillus Botany Biochemistry In vivo Gene Fungus Enzyme Ergosterol |
| Key findings | Five sesquiterpene synthases in Psilocybe cubensis produce distinct sesquiterpenes, with different profiles in mycelium versus fruiting bodies. |
Abstract
Apart from the psychedelic psilocybin, the metabolite spectrum of Psilocybe "magic mushrooms" comprises sesquiterpenes, a class of natural products known to exhibit receptor-modulating bioactivities. However, the composition of the sesquiterpene profile has largely remained an open question. Here, we report the characterization of five Psilocybe cubensis sesquiterpene synthases, both in vitro using recombinantly produced enzymes and in vivo in Aspergillus niger. CubF is a clade I α-muurolol synthase. The investigated clade IV synthases were the near-identical CubG1 and CubG2 synthases, which catalyze mainly epi-isozizaene and β-duprezianene formation. Furthermore, CubH and CubI were identified as primarily making dauca-4(11),8-diene and β-barbatene, respectively. Gas chromatographic analyses of the headspaces of P. cubensis vegetative mycelium and fruiting bodies showed qualitative and quantitative differences, with sterpurene being among the major compounds in mycelium and dauca-4(11),8-diene in fruiting bodies. This fundamental knowledge of the P. cubensis terpenome may help distinguish the pharmacological effects of magic mushrooms versus pure psilocybin.