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Scalable Hybrid Synthetic/Biocatalytic Route to Psilocybin
Authors:Janis Fricke  Dr Robert Kargbo  Dr Lars Regestein  Claudius Lenz  Dr Gundela Peschel  Prof Dr Miriam A Rosenbaum  Dr Alexander Sherwood  Prof Dr Dirk Hoffmeister
Institution:1. Department Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität, Beutenbergstrasse 11a, 07745 Jena, Germany;2. Usona Institute, 2780 Woods Hollow Road, Madison, WI, 53711 USA;3. Bio Pilot Plant, Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Beutenbergstrasse 11a, 07745 Jena, Germany
Abstract:Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment-resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis with the mushroom kinase PsiK. This enzyme was biochemically characterized and used to produce one gram of psilocybin from psilocin within 20 minutes. We also describe a pilot-scale protocol for recombinant PsiK that yielded 150 mg enzyme in active and soluble form. Our work consolidates the simplicity of tryptamine chemistry with the specificity and selectivity of enzymatic catalysis and helps provide access to an important drug at potentially reasonable cost.
Keywords:bioorganic chemistry  biosynthesis  enzymes  fermentation  kinase  phosphorylation
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