Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis
Tim Schäfer, Kristina Kramer, Sebastiaan Werten, Bernhard Rupp, Dirk Hoffmeister
ChemBioChem November 3, 2022 DOI: 10.1002/cbic.202200551 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro biochemical characterization with in silico modeling Peer reviewed |
|---|---|
| Population | Psilocybe cubensis PsiD enzyme |
| Topics | Psilocybin |
| Keywords | Biochemistry Natural product In silico Serine Stereochemistry |
| Citations | 20 |
| Key points | PsiD uses a non-canonical serine protease triad for autocatalytic cleavage, which was predicted and verified by site-directed mutagenesis. |
Abstract
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 phosphatidylserine decarboxylases. Here, we report on the in vitro biochemical characterization of Psilocybe cubensis PsiD along with in silico modeling of the PsiD structure. A non‐canonical serine protease triad for autocatalytic cleavage of the pro‐protein was predicted and experimentally verified by site‐directed mutagenesis.