Chemistry - A European Journal
November 14, 2019
Felix Blei, Sebastian Dörner, Janis Fricke et al.
80 citations
The psychotropic effects of Psilocybe 'magic' mushrooms are caused by the alkaloid psilocybin, but their broader secondary metabolome is poorly understood. Analysis of four Psilocybe species identified harmane, harmine, and other tryptophan-derived β-carbolines as natural products, confirmed by NMR spectroscopy and stable-isotope labeling. MALDI-MS imaging showed β-carbolines accumulate toward hyphal apices. As potent monoamine oxidase inhibitors, these β-carbolines are neuroactive and interfere with psilocybin degradation, representing an unprecedented scenario where different natural product pathways from the same building block contribute directly or indirectly to the same pharmacological effects.
ChemBioChem
April 28, 2022
Claudius Lenz, Sebastian Dörner, Felix Trottmann et al.
26 citations
Psilocybin, the main alkaloid in psychedelic mushrooms, acts as a prodrug to psilocin, a potent psychedelic that alters human consciousness. Its positional isomer bufotenin differs in reported pharmacology. Experiments tested whether psilocin's C-4 hydroxy group influences properties through pseudo-ring formation via an intramolecular hydrogen bond (IMHB). NMR spectroscopy and quantum chemical calculations compared hydrogen bond behavior in 4- and 5-hydroxylated tryptamines. Evidence shows a pseudo-ring in psilocin and that sidechain/hydroxyl interactions affect oxidation kinetics. The propensity to form IMHBs leads to more uncharged species that cross the blood-brain barrier, unlike bufotenin. This helps explain psilocin's pharmacology and supports developing psilocybin as a therapy for major depressive disorder.
ChemBioChem
August 24, 2023
Eike Schäfer, Stefan Bartram, Felix Trottmann et al.
7 citations
Psilocybe 'magic mushrooms' are well known for their psychotropic tryptamines, but the diversity of other specialized metabolites, especially terpenoids, has remained unclear. CubA, the single clade II sesquiterpene synthase from Psilocybe cubensis, was produced in Escherichia coli and characterized in vitro, with additional in vivo assays in Aspergillus niger. GC-MS analyses showed CubA functions as a multi-product synthase, producing cubebol, β-copaene, δ-cadinene, and germacrene D as major products depending on reaction conditions. Analysis of mature P. cubensis mushrooms detected β-copaene and δ-cadinene. Closely related enzymes are encoded in genomes of various Psilocybe species, providing insight into the metabolic capacity of the entire genus.