Scalable Hybrid Synthetic/Biocatalytic Route to Psilocybin
Chemistry - A European Journal – February 26, 2020
Source: OpenAlex
Summary
Producing 1 gram of psilocybin, a key psychedelic alkaloid, in just 20 minutes is now possible using a mushroom enzyme. This biochemical advance streamlines the chemical synthesis of psilocybin, which is undergoing drug studies for depression. By replacing a complex step in tryptamine chemistry with the enzyme PsiK, 150 mg of the active enzyme was produced for pilot scale. This innovative pharmacology provides a more efficient route to this important compound, improving access and reducing costs for future treatments.
Abstract
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.