Credit: Felix Blei/Leibniz-HKI, editedNew study sheds light on the structure and advancement of an enzyme in psychoactive fungi.The psychoactive substance psilocybin is the most essential natural product of so-called “magic mushrooms” of the genus Psilocybe, which makes these mushrooms a popular drug. Accordingly, it formerly just had the ability to connect a single methyl group to the target molecule.The biosynthesis of psilocybin begins with L-tryptophan and involves 2 methylation actions catalyzed by PsiM. Credit: Dirk Hoffmeister/Leibniz-HKI” The psilocybin precursor norbaeocystin, which is converted by PsiM, structurally mimics part of the RNA, but is methylated twice,” says Hoffmeister.A Small Swap With a Big ImpactIn further investigations, the scientists were also able to identify a crucial amino acid exchange that gave PsiM the capability to carry out double methylation throughout development. PsiM can therefore be ruled out for the biosynthetic production of this analog.However, the enzyme could be pertinent for the production of psilocybin in microorganisms in the future: “Overall, our outcomes can help to establish brand-new versions of psilocybin with improved restorative properties and to produce them biotechnologically,” states Hoffmeister.Reference: “Methyl transfer in psilocybin biosynthesis” by Jesse Hudspeth, Kai Rogge, Sebastian Dörner, Maximilian Müll, Dirk Hoffmeister, Bernhard Rupp and Sebastiaan Werten, 28 March 2024, Nature Communications.DOI: 10.1038/ s41467-024-46997-z.
Accordingly, it formerly only had the ability to attach a single methyl group to the target molecule.The biosynthesis of psilocybin begins with L-tryptophan and includes two methylation actions catalyzed by PsiM. Credit: Dirk Hoffmeister/Leibniz-HKI” The psilocybin precursor norbaeocystin, which is converted by PsiM, structurally imitates part of the RNA, but is methylated two times,” says Hoffmeister.A Small Swap With a Big ImpactIn further investigations, the researchers were likewise able to determine a crucial amino acid exchange that offered PsiM the ability to carry out double methylation during development. PsiM can for that reason be ruled out for the biosynthetic production of this analog.However, the enzyme could be relevant for the production of psilocybin in microbes in the future: “Overall, our outcomes can help to develop brand-new variations of psilocybin with improved restorative homes and to produce them biotechnologically,” says Hoffmeister.Reference: “Methyl transfer in psilocybin biosynthesis” by Jesse Hudspeth, Kai Rogge, Sebastian Dörner, Maximilian Müll, Dirk Hoffmeister, Bernhard Rupp and Sebastiaan Werten, 28 March 2024, Nature Communications.DOI: 10.1038/ s41467-024-46997-z.
