ChemBioChemApril 1, 2026Sebastian Schober, Lisa Dorfmann, Karl Walther et al.
Apart from the psychedelic psilocybin, the metabolite spectrum of Psilocybe "magic mushrooms" comprises sesquiterpenes, a class of natural products known to exhibit receptor-modulating bioactivities. However, the composition of the sesquiterpene profile has largely remained an open question. Here, we report the characterization of five Psilocybe cubensis sesquiterpene synthases, both in vitro...
Classic psychedelics such as LSD, psilocybin, and DMT from unregulated markets pose considerable risks through unknown adulterants and potencies. In this chapter, we explore the importance of drug checking in minimizing harm among users of classic psychedelics and examine the opportunities and challenges associated with intervention settings, analytical techniques, and risk communication...
The goal of this doctoral thesis was the close examination of the biosynthesis of different indole alkaloides produced by different species of the fungal genus Psilocybe. This included the first characterization of the biosynthesis of psilocybin as the main psychotropic agent and the first discovery of the simultaneous production of β-carbolines. In the first step, the genome of P. cyanescens...
Abstract The psychotropic effects of Psilocybe “magic” mushrooms are caused by the l ‐tryptophan‐derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other l ‐tryptophan‐derived β‐carbolines as their natural products, which was confirmed...
Abstract Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently being investigated in advanced clinical trials. Here, we report a biocatalytic route to synthesize 6‐methylated psilocybin and baeocystin from 4‐hydroxy‐6‐methyl‐ l...
Abstract Psilocybe mushrooms are best known for their l ‐tryptophan‐derived psychotropic alkaloid psilocybin. Dimethylation of norbaeocystin, the precursor of psilocybin, by the enzyme PsiM is a critical step during the biosynthesis of psilocybin. However, the “magic” mushroom Psilocybe serbica also mono‐ and dimethylates l ‐tryptophan, which is incompatible with the specificity of PsiM. Here,...
Abstract The fungal genus Psilocybe and other genera comprise numerous mushroom species that biosynthesize psilocybin (4‐phosphoryloxy‐ N , N ‐dimethyltryptamine). It represents the prodrug to its dephosphorylated psychotropic analogue, psilocin. The colloquial term “magic mushrooms” for these fungi alludes to their hallucinogenic effects and to their use as recreational drugs. However,...
Abstract Psilocybin (4‐phosphoryloxy‐ N , N ‐dimethyltryptamine) is the main alkaloid of the fungal genus Psilocybe , the so‐called “magic mushrooms.” The pharmaceutical interest in this psychotropic natural product as a future medication to treat depression and anxiety is strongly re‐emerging. Here, we present an enhanced enzymatic route of psilocybin production by adding TrpB, the tryptophan...
Abstract Psilocybin is the psychotropic tryptamine‐derived natural product of Psilocybe carpophores, the so‐called “magic mushrooms”. Although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. We characterized four psilocybin biosynthesis enzymes, namely i) PsiD, which represents a new class of fungal l ‐tryptophan decarboxylases, ii) PsiK,...
Abstract Psilocybin ist der psychotrope, vom Tryptamin abgeleitete Naturstoff der Psilocybe‐Fruchtkörper, der so genannten “Zauberpilze”. Obwohl dessen Struktur seit 60 Jahren bekannt ist, blieb die enzymatische Grundlage ihrer Biosynthese ungeklärt. Wir charakterisierten vier Psilocybin‐Biosyntheseenzyme, nämlich i) PsiD, welches zu einer neuen Klasse pilzlicher l ‐Tryptophan‐Decarboxylasen...