Work

Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis

Year: 2022

Type: article

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.

Source: ChemBioChem

DOI: 10.1002/cbic.202200551

Authors: Tim Schäfer, Kristina Kramer, Sebastiaan Werten, Bernhard Rupp, Dirk Hoffmeister

Institutions: Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI), Friedrich Schiller University Jena, Innsbruck Medical University

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: hybrid

Estimated APC paid: $3,900

Funders: Deutsche Forschungsgemeinschaft, Austrian Science Fund