Psilocybin biosynthesis enhancement through gene source optimization.
Metabolic engineering April 16, 2025 Madeleine R Keller, Madeline G McKinney, Abhishek K Sen et al. 8 citations
Psilocybin, the prodrug to the psychoactive compound in 'magic' mushrooms, is being studied as a treatment for depression and anxiety. Previous biosynthesis in E. coli using genes from Psilocybe cubensis achieved maximum titers of 1.16 g/L. This work tested genes from four psilocybin-producing mushroom species and found that psiD and psiK from P. cubensis performed best, while psiM from Psilocybe cyanescens increased selectivity for the intermediate baeocystin. The strain Gymdi30, with psiM from Gymnopilus dilepis, produced 1.46 ± 0.13 g/L psilocybin, the highest reported titer to date. Comparative proteomic analysis during high and low productivity identified metabolic bottlenecks. This represents a significant improvement toward a biosynthetic manufacturing route for psilocybin.