@Article{dbt_mods_00066812, author = {Sch{\"a}fer, Tim and Sherwood, Alexander and Kirkland, Thomas and Kr{\"u}ger, Thomas and Worbs, Jakob and Kniemeyer, Olaf and Gressler, Markus and Hoffmeister, Dirk}, title = {In Vitro Psilocybin Synthesis by Co‐Immobilized Enzymes}, journal = {Chemistry -- A European Journal}, year = {2025}, month = {May}, day = {22}, publisher = {Wiley-VCH}, address = {Weinheim}, volume = {31}, number = {29}, pages = {1--7}, keywords = {biotechnology; enzyme; immobilization; natural products; psilocybin}, 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 into psilocybin. This facile process i) represents a sustainable approach with reusable enzymes, ii) circumvents the drawbacks of in vivo processes while harnessing the selectivity of enzymatic catalysis and iii) helps access an urgently needed drug candidate.}, note = {Zweitver{\"o}ffentlichung}, issn = {0947-6539}, doi = {10.1002/chem.202501037}, url = {https://www.db-thueringen.de/receive/dbt_mods_00066812}, url = {http://uri.gbv.de/document/gvk:ppn:270935193}, url = {https://doi.org/10.1002/chem.202501037}, file = {:https://www.db-thueringen.de/servlets/MCRFileNodeServlet/dbt_derivate_00068459/CHEM_CHEM202501037.pdf:PDF}, language = {en} }