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Cystathionine Gamma-Lyase Regulate Psilocybin Biosynthesis in Gymnopilus dilepis Mushroom via Amino Acid Metabolism Pathways

Summary

Researchers studying the ‘magic mushroom’ Gymnopilus dilepis discovered that a specific enzyme called CTH plays a crucial role in producing psilocybin, the compound with potential antidepressant effects. By blocking this enzyme, they reduced psilocybin production, but adding a related compound called L-cysteine restored it. This finding suggests that controlling amino acid metabolism could help increase psilocybin production for medical use.

Background

Psilocybin is a potential therapeutic compound for treating depression and other mental health conditions. Previous studies have identified psilocybin biosynthesis gene clusters in fungi, but the regulatory mechanisms controlling psilocybin production remain poorly understood. This study investigates the molecular mechanisms regulating psilocybin synthesis in Gymnopilus dilepis mushrooms.

Objective

To elucidate the molecular mechanism regulating psilocybin synthesis in G. dilepis by examining psilocybin content changes after S-adenosyl-l-homocysteine treatment and in different mushroom parts, and to identify genes associated with psilocybin biosynthesis through transcriptome analysis.

Results

SAH treatment significantly reduced psilocybin content to approximately half that of controls. Psilocybin content in stipes was more than three times higher than in pilei. Transcriptome analysis identified DEGs enriched in cysteine and methionine metabolism, with cystathionine gamma-lyase (CTH) expression positively correlated with psilocybin content. CTH inhibition reduced psilocybin and L-serine levels, which were restored by L-cysteine supplementation.

Conclusion

The study reveals a novel mechanism where cystathionine gamma-lyase regulates psilocybin biosynthesis through amino acid metabolism pathways. L-cysteine regulates psilocybin synthesis by affecting L-serine and 4-hydroxy-L-tryptophan, providing a theoretical basis for improving psilocybin production for biomedical applications.
  • Published in:Journal of Fungi,
  • Study Type:Experimental Research,
  • Source: PMID: 36012858, DOI: 10.3390/jof8080870
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