Journal of Natural Products
September 20, 2017
Claudius Lenz, Jonas Wick, Dirk Hoffmeister
62 citations
A previously unreported natural compound, ω-N-methyl-4-hydroxytryptamine (norpsilocin), was identified in the fruiting bodies of the hallucinogenic mushroom Psilocybe cubensis. Its structure was determined using NMR spectroscopy and high-resolution mass spectrometry. Norpsilocin is likely the actual psychoactive agent released from its phosphate ester derivative, the known natural product baeocystin. The authors also developed a simple extraction method that avoids dephosphorylation, thereby preserving the natural metabolic profile of Psilocybe mushrooms for analysis.
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.
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.
ChemBioChem
August 11, 2018
Felix Blei, Janis Fricke, Jonas Wick et al.
31 citations
Psilocybe mushrooms produce the psychoactive alkaloid psilocybin from L-tryptophan. A newly identified enzyme, TrpM, mono- and dimethylates L-tryptophan itself, unlike the previously known PsiM enzyme that methylates norbaeocystin. TrpM does not act on tryptamine, indicating a second L-tryptophan-dependent pathway separate from psilocybin biosynthesis. TrpM originated from an ancient duplication of part of the egtDB gene, which codes for an ergothioneine biosynthesis enzyme. This duplicated gene was mostly lost during mushroom evolution but independently re-evolved in various genera. The findings suggest a mechanism where weakly selected genes are preserved by being retained within a widely distributed, conserved metabolic pathway.