Clade III Synthases Add Cyclic and Linear Terpenoids to the Psilocybe Metabolome
Nick Zschoche, Markus Gressler, Stefan Bartram, Dirk Hoffmeister, Sebastian Johannes Schober, Karl Walther, Andrew R Chadeayne, Sarah E. O’connor
ChemBioChem May 3, 2025 DOI: 10.1002/cbic.202500167 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Psilocybe cubensis clade III sesquiterpene synthases CubB-CubE |
| Keywords | Biochemistry Sesquiterpene Metabolome Nerolidol Natural product Enzyme Terpenoid Botany |
| Citations | 1 |
| Key findings | Psilocybe cubensis encodes four sesquiterpene synthases—CubB (nerolidol synthase), CubC (multiproduct enzyme), and CubD/CubE (sterpurene-forming)—that are differentially expressed and contribute to the genus's secondary metabolome. |
Abstract
Psilocybe “magic mushrooms” are best known for their indolethylamine psilocybin, yet they encode enzymes for a much more diverse arsenal of small and potentially bioactive molecules. Herein, four Psilocybe cubensis clade III sesquiterpene synthases, CubB‐CubE, whose genes are differently expressed in fruiting bodies compared to vegetative mycelium are reported. CubB‐CubE were functionally characterized in vitro by product formation assays with heterologously produced enzymes and in vivo by transgene expression in Aspergillus niger , followed by extensive gas chromatography‐mass spectrometry analyzes. CubB was identified as a single product (3 R, 6 E )‐(‐) ‐ nerolidol synthase. CubC is a multiproduct enzyme producing β‐caryophyllene, β‐elemene, α‐humulene, and β‐farnesene. CubD and CubE catalyze (near‐)exclusively sterpurene formation. P. cubensis young fruiting bodies and vegetative mycelium were analyzed for sesquiterpenes, which verified the presence of the CubB product α‐(3 R, 6 E )‐(‐) ‐ nerolidol. As various Psilocybe species encode highly similar enzymes, this study contributes generally to the as‐yet little‐understood secondary metabolome of the genus.