In Vitro Psilocybin Synthesis by Co-Immobilized Enzymes.
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ABSTRACT: Advanced clinical trials investigate the Psilocybe magic mushroom natural product psilocybin as a treatment against major depressive disorder. Currently, synthetic material is used to meet the demand for legitimate pharmaceutical purposes. Here, we report an in vitro approach to biocatalytically produce psilocybin on a solid-phase matrix charged with five covalently bound biosynthetic enzymes. These enzymes include three Psilocybe enzymes: IasA*, an engineered l-tryptophan decarboxylase/aromatic aldehyde synthase, the 4-hydroxytryptamine kinase PsiK and the norbaeocystin methyltransferase PsiM, along with Escherichia coli nucleosidase MtnN and adenine deaminase Ade. In a proof-of-principle experiment, this enzyme-charged resin allowed for quantitative turnover of 4-hydroxy-l-tryptophan int
SUBMITTER: Schafer T
PROVIDER: S-EPMC12099186 | biostudies-literature | 2025 May
REPOSITORIES: biostudies-literature
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