Psilocybin, the main psychoactive alkaloid in Psilocybe mushrooms, is being tested as a treatment for depression. Pharmaceutical psilocybin is currently made by synthetic chemistry. Replacing a difficult chemical phosphorylation step with the mushroom enzyme PsiK allowed production of one gram of psilocybin from psilocin in 20 minutes. A pilot-scale protocol also yielded 150 mg of active, soluble PsiK enzyme. This combination of tryptamine chemistry and enzymatic catalysis may provide access to psilocybin at potentially lower cost.
By deleting genes involved in L-tryptophan catabolism, psilocybin production was increased fivefold in baker's yeast and tenfold in the filamentous fungus Aspergillus nidulans. Process optimization in A. nidulans batch cultures yielded a final psilocybin titre of 267 mg/L with a space-time-yield of 3.7 mg/L/h. The engineered strain demonstrates suitability as a production chassis for psilocybin and other tryptamine-derived pharmaceuticals.
A bioprocess using a genetically modified strain of the fungus Aspergillus nidulans produced 542 mg per liter of psilocybin from glucose in 68 hours. The filamentous culture broth was sensitive to oxygen availability and power input, which affected viscosity and mass transfer. Scaling up from shake flasks to a 7-liter stirred tank reactor based on specific power input, along with enhanced oxygen supply in a pressure reactor and nitrogen limitation addressed by adding ammonium sulfate, yielded a robust batch process. This biotechnological approach could supplement chemical synthesis for supplying psilocybin for pharmaceutical use and demonstrates pressurized bioprocessing to overcome oxygen limitations for shear-sensitive filamentous organisms.