Engineering artificial biosynthetic pathways for efficient microbial production of psilocybin and psilocin
Metabolic Engineering November 5, 2025 Cui Guo, Nguyen N T Luu, Maryem M Adwer et al. 5 citations
Psychedelic-assisted therapy is emerging as a promising approach for depression, with psilocybin showing efficacy for post-traumatic stress disorder and treatment-resistant depression, but its low natural abundance makes extraction costly. Engineered microbial production has been limited by dependence on the CYP450 hydroxylase (PsiH) in the natural biosynthetic pathway. Researchers designed, validated, and optimized artificial biosynthetic pathways in Escherichia coli that bypass PsiH, enabling efficient psilocybin and psilocin production. De novo biosynthesis achieved record titers of 557.91 mg/L in shake flasks and 2.00 g/L in a bioreactor, outperforming previous microbial engineering efforts and demonstrating commercial potential via combinatorial metabolic engineering and synthetic biology.