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.
ChemBioChem
May 18, 2022
Sebastian Dörner, Kai Rogge, Janis Fricke et al.
43 citations
Psilocybe magic mushrooms are best known for producing psilocybin and psilocin, but their broader secondary metabolome is poorly understood. Genomes of five species (P. azurescens, P. cubensis, P. cyanescens, P. mexicana, and P. serbica) revealed much greater and unexplored metabolic diversity than chemical analyses alone. P. cyanescens and P. mexicana were identified as aeruginascin producers. Lumichrome and verpacamide A were also detected as Psilocybe metabolites. These findings support efforts to understand phenomena like paralytic effects attributed to some magic mushrooms.
ChemBioChem
December 4, 2019
Richard Demmler, Janis Fricke, Sebastian Dörner et al.
31 citations
Psilocybe cubensis mushrooms produce psilocybin through a five-step pathway that consumes ATP and SAM, requiring efficient recycling of these co-substrates. The adenosine kinase and SAH hydrolase enzymes from the fungus help regenerate SAM. Gene expression increases in fungal primordia and fruiting bodies. A one-pot reaction combining the methyltransferase PsiM with SAH hydrolase shows that removing the byproduct SAH enables continued biosynthesis.
ChemBioChem
August 24, 2023
Eike Schäfer, Stefan Bartram, Felix Trottmann et al.
7 citations
Psilocybe 'magic mushrooms' are well known for their psychotropic tryptamines, but the diversity of other specialized metabolites, especially terpenoids, has remained unclear. CubA, the single clade II sesquiterpene synthase from Psilocybe cubensis, was produced in Escherichia coli and characterized in vitro, with additional in vivo assays in Aspergillus niger. GC-MS analyses showed CubA functions as a multi-product synthase, producing cubebol, β-copaene, δ-cadinene, and germacrene D as major products depending on reaction conditions. Analysis of mature P. cubensis mushrooms detected β-copaene and δ-cadinene. Closely related enzymes are encoded in genomes of various Psilocybe species, providing insight into the metabolic capacity of the entire genus.
Chemistry - A European Journal
April 9, 2025
Tim Schäfer, Thomas Krüger, Jakob Worbs et al.
2 citations
A reusable solid-phase resin coated with five enzymes—three from Psilocybe mushrooms and two from E. coli—converts 4-hydroxy-L-tryptophan into psilocybin quantitatively in a proof-of-principle in vitro experiment. This biocatalytic approach offers a sustainable, selective alternative to synthetic production for the drug candidate being tested in advanced clinical trials for major depressive disorder.
ChemBioChem
May 3, 2025
Nick Zschoche, Markus Gressler, Stefan Bartram et al.
1 citation
Psilocybe cubensis mushrooms, famous for producing the psychedelic compound psilocybin, also possess enzymes that synthesize a variety of other small, potentially bioactive molecules. Four newly identified sesquiterpene synthases, CubB through CubE, are expressed differently in the mushroom's fruiting bodies versus its vegetative mycelium. CubB produces a single compound, nerolidol, while CubC generates multiple sesquiterpenes including β-caryophyllene and α-humulene. CubD and CubE nearly exclusively produce sterpurene. The presence of nerolidol was confirmed in young fruiting bodies and vegetative mycelium. These findings expand understanding of the secondary metabolome of Psilocybe species.
ChemBioChem
April 1, 2026
Sebastian Schober, Lisa Dorfmann, Karl Walther et al.
Psilocybe cubensis magic mushrooms produce not only the psychedelic psilocybin but also a range of sesquiterpenes, natural products that can modulate biological receptors. Five sesquiterpene synthases were characterized: CubF makes α-muurolol, CubG1 and CubG2 produce mainly epi-isozizaene and β-duprezianene, CubH yields dauca-4(11),8-diene, and CubI forms β-barbatene. Gas chromatography revealed that vegetative mycelium and fruiting bodies have different sesquiterpene profiles, with sterpurene prominent in mycelium and dauca-4(11),8-diene in fruiting bodies. This knowledge may help separate the pharmacological effects of whole magic mushrooms from those of pure psilocybin.