Clade III Synthases Add Cyclic and Linear Terpenoids to the Psilocybe Metabolome
ChemBioChem – May 03, 2025
Source: OpenAlex
Summary
*Psilocybe* mushrooms, known in Psychedelics and Drug Studies, produce a much richer array of natural products than just psilocybin. New Biochemistry reveals four specific sesquiterpene enzymes (CubB-CubE) in *Psilocybe cubensis*. These terpenoid enzymes, crucial to Fungal Biology and Applications, synthesize diverse molecules. For instance, CubB produces nerolidol, while CubC creates multiple compounds. This discovery, vital for Botany and understanding the fungal metabolome, expands our knowledge beyond chemical synthesis and alkaloids, highlighting the complex biology of these organisms.
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.