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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |
Citations in the library
Cited by 14
- “Biosynthesis of psilocybin and its nonnatural derivatives by a promiscuous psilocybin synthesis pathway in Escherichia coli” Biotechnology and Bioengineering June 20, 2023
- Methyl transfer in psilocybin biosynthesis Nature Communications March 28, 2024
- Genetic regulation of L-tryptophan metabolism in Psilocybe mexicana supports psilocybin biosynthesis. Fungal biology and biotechnology April 25, 2024
- Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms Angewandte Chemie International Edition September 21, 2025
- Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications Biotechnology Progress October 4, 2024
and 9 more in the library
Cites 17
- Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose?effect study Psychopharmacology March 1, 2004
- Psilocybin – Summary of knowledge and new perspectives European Neuropsychopharmacology December 17, 2013
- Enzymatic Synthesis of Psilocybin Angewandte Chemie International Edition August 1, 2017
- Psilocybin: from ancient magic to modern medicine The Journal of Antibiotics May 12, 2020
- Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives Metabolic Engineering March 26, 2020
and 12 more in the library