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.
Chemistry - A European Journal
July 16, 2018
Janis Fricke, Claudius Lenz, Jonas Wick et al.
52 citations
Psilocybin, the prodrug to the psychotropic compound psilocin, is biosynthesized by numerous mushroom species in the fungal genus Psilocybe and other genera, colloquially known as 'magic mushrooms' for their hallucinogenic effects and recreational use. Clinical trials have recognized psilocybin as a valuable candidate for development into a medication against depression and anxiety. This review highlights the recently elucidated biosynthesis of psilocybin, the concurrently developed concept of enzymatic in vitro and heterologous in vivo production, along with previous synthetic routes. The prospect of psilocybin as a promising therapeutic may entail increased demand, which can be met by biotechnological production. The review also briefly touches on psilocybin's therapeutic relevance and pharmacology.
Chemistry - A European Journal
May 11, 2018
Felix Blei, Florian Baldeweg, Janis Fricke et al.
51 citations
Psilocybin, the main psychoactive alkaloid in 'magic mushrooms,' is being investigated as a potential treatment for depression and anxiety. This work describes an improved method for producing psilocybin enzymatically by adding the mushroom enzyme tryptophan synthase (TrpB) to the reaction. The new route uses cheaper starting materials—4-hydroxyindole and L-serine—to form psilocybin. The same approach also produced two other compounds: a non-natural alkaloid called isonorbaeocystin and the neurotransmitter serotonin. This enzymatic method offers a more cost-effective way to synthesize psilocybin and related molecules for research and potential pharmaceutical use.
Chemistry - A European Journal
February 26, 2020
Janis Fricke, Robert B. Kargbo, Lars Regestein et al.
48 citations
Psilocybin, the main psychoactive alkaloid in Psilocybe mushrooms, is being tested as a treatment for depression. Pharmaceutical psilocybin is currently made by synthetic chemistry. Replacing a difficult chemical phosphorylation step with the mushroom enzyme PsiK allowed production of one gram of psilocybin from psilocin in 20 minutes. A pilot-scale protocol also yielded 150 mg of active, soluble PsiK enzyme. This combination of tryptamine chemistry and enzymatic catalysis may provide access to psilocybin at potentially lower cost.
Chemistry - A European Journal
June 1, 2021
Claudius Lenz, Sebastian Dörner, Alexander Sherwood et al.
19 citations
Psilocin, the psychoactive compound derived from psilocybin, turns blue when mushrooms containing it are bruised. This blue color was previously thought to come from a specific chemical dimer (5,5'-coupled quinone). By synthesizing stable, ring-methylated derivatives of psilocin and analyzing their oxidized forms with spectroscopy and computational modeling, researchers showed that the blue color actually arises from a different dimer (7,7'-coupled quinoid). The original hypothesis was not supported.
Chemistry - A European Journal
April 9, 2025
Tim Schäfer, Thomas Krüger, Jakob Worbs et al.
2 citations
A reusable solid-phase resin coated with five enzymes—three from Psilocybe mushrooms and two from E. coli—converts 4-hydroxy-L-tryptophan into psilocybin quantitatively in a proof-of-principle in vitro experiment. This biocatalytic approach offers a sustainable, selective alternative to synthetic production for the drug candidate being tested in advanced clinical trials for major depressive disorder.