Bacterial production of psilocybin and 13 related compounds was achieved by adding the enzyme PsiH to the existing biosynthesis pathway. Testing 49 different indole derivatives revealed that the pathway enzymes accept many substrates, enabling the creation of a library of new drug candidates for mental health treatment.
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.