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Bernhard Rupp

7 papers in the library · 94 citations · publishing 2019-2025

Papers

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Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms

Angewandte Chemie International Edition September 21, 2025 Tim Schäfer, Fabian Haun, Bernhard Rupp et al. 7 citations

Abstract Psilocybin (4‐phosphoryloxy‐ N , N ‐dimethyltryptamine, 1 ) is the main indolethyl‐amine natural product of psychotropic (so‐called “magic”) mushrooms. The majority of 1 ‐producing species belongs to the eponymous genus Psilocybe , for which the biosynthetic events, beginning from l ‐tryptophan ( 2 ), and the involved enzymes have thoroughly been characterized. Some Inocybe (fiber cap)...

Unterschiedliche Reaktionen und Enzyme in der Psilocybin‐ Biosynthese bei Inocybe‐ und Psilocybe ‐Pilzen

Angewandte Chemie September 21, 2025 Tim Schäfer, Fabian Haun, Bernhard Rupp et al.

Zusammenfassung Psilocybin (4‐Phosphoryloxy‐ N , N ‐dimethyltryptamin, 1 ) ist der hauptsächliche Indolethylamin‐Naturstoff der psychotropen sogenannten Zauberpilze. Die Mehrheit der 1 ‐produzierenden Arten gehört zu der namensgebenden Gattung Psilocybe , für die die biosynthetischen Ereignisse, ausgehend von l ‐Tryptophan ( 2 ), sowie die beteiligten Enzyme gründlich charakterisiert wurden....

Substrate recognition by the 4‐hydroxytryptamine kinase PsiK in psilocybin biosynthesis

FEBS Letters October 24, 2024 Kai Rogge, Tobias Wagner, Dirk Hoffmeister et al. 4 citations

Psilocybin, the natural hallucinogen from Psilocybe (magic) mushrooms, is a highly promising drug candidate for the treatment of depression and several other mental health conditions. Biosynthesis of psilocybin from the amino acid l‐ tryptophan involves four strictly sequential modifications. The third of these, ATP‐dependent phosphorylation of the intermediate 4‐hydroxytryptamine, is catalysed...

The Second Methylation in Psilocybin Biosynthesis Is Enabled by a Hydrogen Bonding Network Extending into the Secondary Sphere Surrounding the Methyltransferase Active Site

ChemBioChem October 16, 2024 Jesse Hudspeth, Kai Rogge, Tobias Wagner et al. 1 citation

Abstract The Psilocybe cubensis SAM‐dependent methyltransferase, PsiM, catalyzes the last step in the biosynthesis of psilocybin. Likely evolved from monomethylating RNA methyltransferases, PsiM acquired a key amino acid exchange in the secondary sphere of the active site, M247 N, which is responsible for its capacity to dimethylate. Two variants, PsiM N247M and PsiM N247A , were generated to...

Methyl transfer in psilocybin biosynthesis

Nature Communications March 28, 2024 Jesse Hudspeth, Kai Rogge, Sebastian Dörner et al. 24 citations

Abstract Psilocybin, the natural hallucinogen produced by Psilocybe (“magic”) mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolution (0.9 Å) crystal structures of...

Characterization of the Gateway Decarboxylase for Psilocybin Biosynthesis

ChemBioChem November 3, 2022 Tim Schäfer, Kristina Kramer, Sebastiaan Werten et al. 20 citations

Abstract The l ‐tryptophan decarboxylase PsiD catalyzes the initial step of the metabolic cascade to psilocybin, the major indoleethylamine natural product of the “magic” mushrooms and a candidate drug against major depressive disorder. Unlike numerous pyridoxal phosphate (PLP)‐dependent decarboxylases for natural product biosyntheses, PsiD is PLP‐independent and resembles type II...

Enzymatic Route toward 6‐Methylated Baeocystin and Psilocybin

ChemBioChem May 31, 2019 Janis Fricke, Alexander M. Sherwood, Robert B. Kargbo et al. 38 citations

Abstract Psilocybin and its direct precursor baeocystin are indole alkaloids of psychotropic Psilocybe mushrooms. The pharmaceutical interest in psilocybin as a treatment option against depression and anxiety is currently being investigated in advanced clinical trials. Here, we report a biocatalytic route to synthesize 6‐methylated psilocybin and baeocystin from 4‐hydroxy‐6‐methyl‐ l...