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.