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Genetic regulation of l-tryptophan metabolism in Psilocybe mexicana supports psilocybin biosynthesis

Summary

Researchers studied how magic mushrooms (Psilocybe mexicana) regulate their chemistry to produce psilocybin, the psychoactive compound. They found that when mushrooms start fruiting, they turn on genes that make tryptophan (an amino acid building block) and turn off genes that break it down, directing all the tryptophan toward psilocybin production. This coordinated genetic control ensures the mushroom has enough of this key ingredient. This knowledge could help grow these mushrooms in labs for legitimate medical research into treating depression.

Background

Basidiomycota fungi produce pharmaceutically relevant natural products, but knowledge of how they coordinate primary and secondary metabolism is limited. Psilocybe mushrooms produce psilocybin, a psychedelic alkaloid that can comprise up to 2% of dry mass, requiring substantial l-tryptophan supply during fruiting body formation.

Objective

This study investigated whether l-tryptophan biosynthesis and degradation genes in Psilocybe mexicana correlate with psilocybin production using genetic, transcriptomic, and biochemical approaches.

Results

Tryptophan biosynthesis genes trpE1, trpD, and trpB were upregulated 2.7 to 10.5-fold in carpophores, while tryptophan-consuming genes idoA and iasA were massively downregulated. IasA was identified as the first characterized microbial l-tryptophan-preferring indole-3-acetaldehyde synthase. Species-specific differences in gene regulation were found between P. mexicana and P. cubensis despite their close relationship.

Conclusion

The coordinated upregulation of l-tryptophan biosynthesis genes and downregulation of tryptophan-consuming genes reflects a well-adjusted cellular system routing this amino acid toward psilocybin production, providing the first insight into coordination of mushroom primary and secondary metabolism.
  • Published in:Fungal Biology and Biotechnology,
  • Study Type:Research Study,
  • Source: 10.1186/s40694-024-00173-6, PMID: 38664850
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