Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms
Tim Schäfer, Fabian Haun, Bernhard Rupp, Dirk Hoffmeister
Angewandte Chemie International Edition September 21, 2025 DOI: 10.1002/anie.202512017 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro study Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Citations | 7 |
| Key points | The psilocybin biosynthetic pathway in Inocybe corydalina is branched and uses different enzymes than in Psilocybe species, indicating independent evolution of psilocybin production. |
Abstract
Abstract Psilocybin (4‐phosphoryloxy‐ N , N ‐dimethyltryptamine, 1 ) is the main indolethyl‐amine natural product of psychotropic (so‐called “magic”) mushrooms. The majority of 1 ‐producing species belongs to the eponymous genus Psilocybe , for which the biosynthetic events, beginning from l ‐tryptophan ( 2 ), and the involved enzymes have thoroughly been characterized. Some Inocybe (fiber cap) species, among them Inocybe corydalina , produce 1 as well. In product formation assays, we characterized four recombinantly produced biosynthesis enzymes of this species in vitro: IpsD, a pyridoxal‐5′‐phosphate‐dependent l ‐tryptophan decarboxylase, the kinase IpsK, and two near‐identical methyltransferases, IpsM1 and IpsM2. The fifth enzyme, the insoluble monooxygenase IpsH, was analyzed in silico. Surprisingly, none of the reactions intrinsic to the 1 pathway in Psilocybe species takes place in I. corydalina . Contrasting the situation in Psilocybe , the Inocybe pathway is branched and leads to baeocystin (4‐phosphoryloxy‐ N ‐methyltryptamine, 3 ) as a second end product. Our results demonstrate that mushrooms recruited distantly or entirely unrelated enzymes to evolve the metabolic capacity for 1 biosynthesis twice independently.
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 3
- Chemical ecology and convergent evolution of natural hallucinogens: From ecological defense to conserved neural targets Proceedings of the National Academy of Sciences June 24, 2026
- Wherefore the Magic? The Evolutionary Role of Psilocybin in Nature Ecology and Evolution April 1, 2026
- The one that abstained: Psilocybe fuscofulva genome suggests two recent origins of the psilocybin gene cluster in Psilocybe bioRxiv (Cold Spring Harbor Laboratory) January 2, 2026
Cites 36
- Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen Helvetica Chimica Acta 1959
- Enzymatic Synthesis of Psilocybin Angewandte Chemie International Edition August 1, 2017
- DARK Classics in Chemical Neuroscience: Psilocybin ACS Chemical Neuroscience June 29, 2018
- Metabolic engineering of Saccharomyces cerevisiae for the de novo production of psilocybin and related tryptamine derivatives Metabolic Engineering March 26, 2020
- Horizontal gene cluster transfer increased hallucinogenic mushroom diversity Evolution Letters February 27, 2018
and 31 more in the library