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Updated: Aug 23, 2025

Enzymatic Cascade Reactions for the Synthesis of Chiral Amino Alcohols from L-lysine
Published on: February 16, 2018
Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis
Tim Schäfer1, Kristina Kramer1, Sebastiaan Werten2
1Department Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität, Beutenbergstrasse 11a, 07745, Jena, Germany.
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.
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