Synthetic Biology and Its Biomedical Applications

Depression affects over 280 million individuals globally and remains a leading cause of disability and suicide. Amid growing interest in psychedelic-assisted therapies, psilocybin—a psychoactive compound derived from magic mushrooms—has emerged as a promising antidepressant, demonstrating rapid and sustained efficacy in clinical trials for major depressive disorder, PTSD, and treatment-resistant depression. However, scalable production of psilocybin and its active metabolite, psilocin, remains a major bottleneck due to low natural abundance and complex chemical synthesis. In this seminar, I will introduce my research program in synthetic biology, with a focus on microbial biomanufacturing of pharmaceutically relevant compounds. I will present our recent work on engineering E. coli for de novo biosynthesis of psilocybin and psilocin, bypassing key enzymatic limitations in the native fungal pathway. Through rational pathway design, metabolic rewiring, and fermentation optimization, we achieved record titers of 2.00 g/L psilocybin in fed-batch cultures—surpassing existing microbial platforms in both yield and productivity. This work not only demonstrates the power of synthetic biology for scalable production of complex natural products but also lays the groundwork for next-generation delivery strategies, including in situ biosynthesis via engineered gut microbiota. By bridging microbial engineering with psychiatric medicine, this project exemplifies the translational potential of synthetic biology within biomedical engineering and opens new avenues for interdisciplinary collaboration in therapeutic development.