FEBS Letters
October 24, 2024
Kai Rogge, Tobias Wagner, Dirk Hoffmeister et al.
4 citations
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...
ChemBioChem
October 16, 2024
Jesse Hudspeth, Kai Rogge, Tobias Wagner et al.
1 citation
Abstract The Psilocybe cubensis SAM‐dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiM N247M and PsiM N247A , were generated to...
Nature Communications
March 28, 2024
Jesse Hudspeth, Kai Rogge, Sebastian Dörner et al.
24 citations
Abstract Psilocybin, the natural hallucinogen produced by Psilocybe (“magic”) mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolution (0.9 Å) crystal structures of...
ChemBioChem
November 3, 2022
Tim Schäfer, Kristina Kramer, Sebastiaan Werten et al.
20 citations
Abstract The l ‐tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the “magic” mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)‐dependent decarboxylases for natural product biosyntheses, PsiD is PLP‐independent and resembles type II...