|
|||||
|
|
Enzymatic Route toward 6-Methylated Baeocystin and Psilocybin |
|
| Authors: | Janis Fricke Dr Alexander Sherwood Dr Robert Kargbo Dr Andrew Orry Felix Blei Dr Andreas Naschberger Dr Bernhard Rupp Prof Dr Dirk Hoffmeister |
| Affiliation: | 1. Department Pharmaceutical Microbiology at the Hans Knöll Institute, Friedrich-Schiller-Universität, Beutenbergstrasse 11a, 07745 Jena, Germany;2. The Usona Institute, 2800 Woods Hollow Road, Madison, WI, 53711 USA;3. Molsoft L.L.C., 11199 Sorrento Valley Road, San Diego, CA, 92121 USA;4. Department of Genetic Epidemiology, Medizinische Universität Innsbruck, Schöpfstrasse 41, 6020 Innsbruck, Austria;5. Department of Genetic Epidemiology, Medizinische Universität Innsbruck, Schöpfstrasse 41, 6020 Innsbruck, Austria
Hofkristallamt, 991 Audrey Place, Vista, CA, 92084 USA |
| 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 -tryptophan, which was decarboxylated and phosphorylated by the Psilocybe cubensis biosynthesis enzymes PsiD and PsiK. N-Methylation was catalyzed by PsiM. We further present an in silico structural model of PsiM that revealed a well-conserved SAM-binding core along with peripheral nonconserved elements that likely govern substrate preferences. |
| Keywords: | baeocystin biosynthesis enzymes methyltransferase psilocybin |