Substrate recognition by the 4‐hydroxytryptamine kinase PsiK in psilocybin biosynthesis
Kai Rogge, Tobias Wagner, Dirk Hoffmeister, Bernhard Rupp, Sebastiaan Werten
FEBS Letters October 24, 2024 DOI: 10.1002/1873-3468.15042 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Structural and mutagenesis study Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Biochemistry Kinase Biosynthesis Hallucinogen Mutagenesis Phosphorylation Enzyme |
| Citations | 4 |
| Key points | Crystallographic analysis and structure-based mutagenesis of the kinase PsiK provide insight into its mode of substrate recognition, supporting future bioengineering of psilocybin variants with enhanced therapeutic properties. |
Abstract
Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l‐ tryptophan involves four strictly sequential modifications. The third of these, ATP‐dependent phosphorylation of the intermediate 4‐hydroxytryptamine, is catalysed by PsiK. Here we present a crystallographic analysis and a structure‐based mutagenesis study of this kinase, providing insight into its mode of substrate recognition. The results of our work will support future bioengineering efforts aimed at generating variants of psilocybin with enhanced therapeutic properties.
Citations in the library
Cited by 4
- Exploring Psilocybe cubensis Strains: Cultivation Techniques, Psychoactive Compounds, Genetics and Research Gaps Journal of Fungi January 28, 2025
- Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms Angewandte Chemie International Edition September 21, 2025
- Pathway engineering for the biosynthesis of psychedelics Current Opinion in Biotechnology May 15, 2025
- Unterschiedliche Reaktionen und Enzyme in der Psilocybin‐ Biosynthese bei Inocybe‐ und Psilocybe ‐Pilzen Angewandte Chemie September 21, 2025
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- Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives Metabolic Engineering March 26, 2020
and 20 more in the library