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Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms

Summary

This study reveals that two different types of magic mushrooms—Psilocybe and Inocybe—make psilocybin (the active compound in magic mushrooms) using completely different enzymes and chemical pathways. Despite both mushroom types producing the same final product, they evolved their recipes independently, like two chefs arriving at the same dish through entirely different cooking methods. The research shows how evolution can solve the same problem in multiple ways and provides new enzymes that could be useful for producing psilocybin as a potential depression treatment.

Background

Psilocybin is the main psychotropic compound in magic mushrooms, primarily associated with Psilocybe species. The biosynthetic pathway and enzymes for psilocybin production in Psilocybe have been thoroughly characterized. However, some Inocybe species, including Inocybe corydalina, also produce psilocybin despite lacking the same psi genes found in Psilocybe species.

Objective

To characterize the biosynthetic enzymes and pathway for psilocybin production in Inocybe corydalina and compare them with the established Psilocybe pathway. The study aimed to demonstrate that mushrooms independently evolved different enzymatic strategies to produce the same compound.

Results

The Inocybe pathway is entirely distinct from Psilocybe, with no shared reactions despite both producing psilocybin. IpsD is a PLP-dependent decarboxylase specific for 4-hydroxy-L-tryptophan, contrasting with the PLP-independent PsiD. The pathway is branched, producing both psilocybin and baeocystin as end products, with the order of methylation and phosphorylation reversed compared to Psilocybe. Both methyltransferases are required for efficient psilocybin production.

Conclusion

Mushrooms evolved psilocybin biosynthesis independently at least twice, recruiting distantly or entirely unrelated enzymes. Despite both pathways converging on 4-hydroxytryptamine as a common intermediate, no individual reactions are shared. The findings demonstrate convergent evolution within the mushroom order Agaricales and expand the toolkit for biotechnological psilocybin production.
  • Published in:Angewandte Chemie International Edition,
  • Study Type:Biochemical Characterization Study,
  • Source: PMID: 40977073, DOI: 10.1002/anie.202512017
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