In Vitro Psilocybin Synthesis by Co‐Immobilized Enzymes
Tim Schäfer, Thomas Krüger, Jakob Worbs, Olaf Kniemeyer, Markus Gressler, Dirk Hoffmeister, Alexander M. Sherwood, Thomas A. Kirkland
Chemistry - A European Journal April 9, 2025 DOI: 10.1002/chem.202501037 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro proof-of-principle experiment Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Enzyme Biochemistry Tryptamine In vitro Transferase Combinatorial chemistry Pharmacology |
| Citations | 2 |
| Key findings | An enzyme-charged resin achieves quantitative turnover of 4-hydroxy-L-tryptophan into psilocybin in vitro. |
Abstract
Abstract Advanced clinical trials investigate the Psilocybe magic mushroom natural product psilocybin as a treatment against major depressive disorder. Currently, synthetic material is used to meet the demand for legitimate pharmaceutical purposes. Here, we report an in vitro approach to biocatalytically produce psilocybin on a solid‐phase matrix charged with five covalently bound biosynthetic enzymes. These enzymes include three Psilocybe enzymes: IasA*, an engineered l ‐tryptophan decarboxylase/aromatic aldehyde synthase, the 4‐hydroxytryptamine kinase PsiK and the norbaeocystin methyltransferase PsiM, along with Escherichia coli nucleosidase MtnN and adenine deaminase Ade. In a proof‐of‐principle experiment, this enzyme‐charged resin allowed for quantitative turnover of 4‐hydroxy‐ l ‐tryptophan into psilocybin. This facile process i) represents a sustainable approach with reusable enzymes, ii) circumvents the drawbacks of in vivo processes while harnessing the selectivity of enzymatic catalysis and iii) helps access an urgently needed drug candidate.
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 2
Cites 23
- 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 18 more in the library