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Clade III Synthases Add Cyclic and Linear Terpenoids to the Psilocybe Metabolome

Summary

Researchers identified four enzymes in magic mushrooms that produce various aromatic compounds called terpenes. These findings show that Psilocybe mushrooms make a much wider variety of bioactive molecules beyond just psilocybin. Understanding these additional compounds could help explain why whole mushrooms may have different effects than pure psilocybin alone.

Background

Psilocybe mushrooms are primarily known for psilocybin, but they encode enzymes for diverse bioactive compounds. Understanding the full secondary metabolome of Psilocybe is important given recent changes in legal status and potential consumption increases.

Objective

To characterize four Psilocybe cubensis clade III sesquiterpene synthases (CubB-CubE) that are differentially expressed between fruiting bodies and vegetative mycelium, and to identify their terpene products.

Results

CubB was identified as a bifunctional synthase producing (3R,6E)-(−)-nerolidol with FPP and (3R)-(−)-linalool with GPP. CubC is a multiproduct enzyme producing β-caryophyllene, β-elemene, α-humulene, and β-farnesene. CubD and CubE predominantly catalyze sterpurene formation. These products were verified in P. cubensis tissues.

Conclusion

Four clade III terpene synthases add diverse cyclic and linear sesquiterpenes to the Psilocybe metabolome. These findings contribute to understanding the complete secondary metabolite diversity of this genus and provide insights relevant to understanding the entourage effect of psilocybin-containing mushrooms.
  • Published in:ChemBioChem,
  • Study Type:Experimental Research,
  • Source: PMID: 40318115, DOI: 10.1002/cbic.202500167
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