Angewandte Chemie International Edition
August 1, 2017
Janis Fricke, Felix Blei, Dirk Hoffmeister
210 citations
Psilocybin, the psychoactive compound in magic mushrooms, is synthesized from tryptophan by four fungal enzymes: PsiD (a decarboxylase), PsiK (a kinase), PsiM (a methyltransferase), and PsiH (a monooxygenase). Using a combined reaction of PsiD, PsiK, and PsiM, the authors produced psilocybin enzymatically from 4-hydroxy-L-tryptophan in fewer steps than previously possible. This work identifies the complete biosynthetic pathway, which had been unknown for 60 years, and may enable biotechnological production of psilocybin for pharmaceutical use.
Angewandte Chemie International Edition
November 14, 2019
Claudius Lenz, Jonas Wick, Daniel Braga et al.
56 citations
When psilocybin-producing mushrooms are injured, they turn blue due to a two-step enzymatic cascade. The phosphatase PsiP removes a phosphate group from psilocybin to yield psilocin, and the enzyme PsiL oxidizes psilocin's 4-hydroxy group. This oxidation triggers the formation of blue oligomers, primarily linked at carbon-5, as shown by carbon-13 NMR. Mass and infrared spectroscopy reveal a mixture of psilocyl chains ranging from 3 to 13 units long, with multiple pathways depending on oxidant strength and substrate concentration. The findings suggest that psilocybin's phosphate group acts as a reversible protective modification, preventing premature bluing until injury occurs.
Angewandte Chemie International Edition
September 21, 2025
Tim Schäfer, Fabian Haun, Bernhard Rupp et al.
7 citations
Psilocybin, the main psychoactive compound in magic mushrooms, is also produced by some Inocybe species. Researchers characterized four enzymes from Inocybe corydalina and found that none of the reactions used in Psilocybe species occur in this species. Instead, the Inocybe pathway is branched and produces baeocystin as a second end product. These results show that mushrooms evolved the ability to make psilocybin twice independently, using distantly related or entirely different enzymes.
Angewandte Chemie International Edition
June 17, 2025
Ahram Kim, Nicolás M. Morato, Prabir Saha et al.
4 citations
The enzyme PsiK, which selectively phosphorylates psilocin during psilocybin biosynthesis in Psilocybe cubensis, can also phosphorylate a wide range of substituted phenols and benzenediols beyond its natural substrate. This expands the scope of biocatalytic phosphorylation for synthetic chemistry. Active site mutations further broaden substrate scope and improve site-selectivity, with engineering expedited by DESI-MS screening that analyzed 2688 reactions in 40 minutes. Gram-scale phosphorylation of a representative substrate achieved a turnover number over 10,000. These results highlight PsiK's utility for selective phosphorylation under mild conditions.