ArticleNature communications2025
Structural basis for psilocybin biosynthesis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Reconstituting a two-step pathway forMetabolic engineering communications · 2026Article
- Structural insights into a dual-substrate O-methyltransferase reveal the enzymatic mechanism of parallel paeonol biosynthesis.Nature communications · 2026Article
- Psilocybin modulates social behaviour in male and female mice in a time-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms.Angewandte Chemie (International ed. in English) · 2025Article
- Reaction Engineering of In Vitro Natural Product Biosynthesis: Challenges and Strategies.Chembiochem : a European journal of chemical biology · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Psilocybin shows significant therapeutic potential for psilocybin-assisted psychotherapy in addressing various psychiatric conditions. The biosynthetic approach promises rapid and efficient production of psilocybin. Understanding the enzymes that contribute to the biosynthesis of psilocybin can enhance its production process. In this study, we elucidate the crystal structures of L-tryptophan-specific decarboxylase PsiD in both its apo and tryptamine-bound states, the 4-hydroxytryptamine kinase PsiK bound to its substrate, and several forms of the methyltransferase PsiM in either apo or substrate-bound forms derived from the psychedelic mushroom. Structure-based evaluations reveal the mechanisms of self-cleavage and self-inhibition in PsiD, along with the sequential catalytic steps from 4-hydroxytryptamine to the final compound, psilocybin. Additionally, we showcase the antidepressant properties of biosynthetic intermediates of psilocybin on female mice experiencing depression-like behaviors induced by sub-chronic variable stress. Our studies establish a structural basis for the future biosynthetic production of psilocybin using these enzymes and emphasize the clinical potential of norbaeocystin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.