Enzymatic Route toward 6‐Methylated Baeocystin and Psilocybin
Janis Fricke, Alexander M. Sherwood, Robert B. Kargbo, Andrew Orry, Felix Blei, Andreas Naschberger, Bernhard Rupp, Dirk Hoffmeister
ChemBioChem May 31, 2019 DOI: 10.1002/cbic.201900358 via OpenAlex
Summary
AI-generated from the abstractPsilocybin and its precursor baeocystin are indole alkaloids from psychotropic Psilocybe mushrooms, currently under clinical investigation for depression and anxiety. A biocatalytic route was developed to synthesize 6-methylated psilocybin and baeocystin from 4-hydroxy-6-methyl-L-tryptophan, using the Psilocybe cubensis enzymes PsiD and PsiK for decarboxylation and phosphorylation, and PsiM for N-methylation. An in silico structural model of PsiM revealed a well-conserved SAM-binding core with peripheral nonconserved elements that likely determine substrate preferences.
Study at a glance
| Characteristics | Experimental study with in silico modeling Peer reviewed |
|---|---|
| Topics | Psilocybin |
| Keywords | Enzyme Indole test Methylation In silico |
| Citations | 38 |
| Key finding | A biocatalytic route using Psilocybe cubensis enzymes PsiD, PsiK, and PsiM successfully synthesized 6-methylated psilocybin and baeocystin, with an in silico model of PsiM identifying conserved and variable structural elements influencing substrate specificity. |
Abstract
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.