Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis

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.

Automated summary

This study characterized the in vitro biochemical properties of Psilocybe cubensis PsiD and performed in silico modeling of its structure. The experimental results confirmed the autocatalytic cleavage of the pro-protein by a non-canonical serine protease triad.