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Updated: Jun 29, 2025
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Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
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Methyl transfer in psilocybin biosynthesis
Jesse Hudspeth1,2, Kai Rogge3,4, Sebastian Dörner3,4
1Institute of Genetic Epidemiology, Medical University of Innsbruck, Innsbruck, Austria.
Nature Communications
|March 29, 2024
Summary
This study reveals the atomic structure of PsiM, an enzyme crucial for psilocybin biosynthesis. Understanding this mechanism aids in developing new psilocybin-based therapeutics for mental health conditions.
Area of Science:
- Biochemistry
- Structural Biology
- Pharmacology
Background:
- Psilocybin, a compound from "magic" mushrooms, shows potential for treating mental health disorders.
- The enzyme PsiM catalyzes the final dimethylation step in psilocybin biosynthesis.
Purpose of the Study:
- To elucidate the atomic resolution structure of PsiM.
- To understand the SAM-dependent methylation mechanism of PsiM.
- To explore the evolutionary origins and limitations of PsiM.
Main Methods:
- X-ray crystallography at 0.9 Å resolution.
- Structural and phylogenetic analyses.
- Substrate binding analysis.
Main Results:
- Atomic structures of PsiM captured during its reaction cycle.
- Detailed insights into the SAM-dependent methylation mechanism.
- PsiM shares ancestry with epitranscriptomic N⁶-methyladenosine writers (METTL16 family).
- Bound substrates mimic RNA, suggesting evolutionary links.
Conclusions:
- The study provides a mechanistic understanding of PsiM.
- Inherent limitations of PsiM's scaffold restrict psilocybin production efficiency.
- Findings will guide bioengineering efforts for improved psilocybin analogs.
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