뉴스&공지 KAIST Graduate School of Engineering Biology

Reprogramming Life: Systems Metabolic Engineering from Microbial Cell Factories to Mammalian Therapeutics

Living organisms, from microbes to mammals, rely on complex metabolic networks to sustain life. Systems Metabolic Engineering (SME)-a multidisciplinary strategy integrating metabolic engineering, systems biology, and synthetic biology-has revolutionized our ability to rationally redesign these networks.

In microbial platforms, SME has been successfully applied to construct high-performance cell factories for sustainable chemical production. By integrating multi-omics analyses with computational modeling, we systematically identified metabolic bottlenecks and rewired cellular pathways to achieve world-leading production of industrially relevant compounds. These efforts extended beyond laboratory scale optimization to pilot-scale validation, demonstrating both scalability and economic feasibility, and establishing SME as a powerful platform for advancing bio-based manufacturing.

Expanding this strategy beyond microbial platforms, we applied SME into mammalian systems to address a fundamental evolutionary constraint: the loss of essential amino acid (EAA) biosynthesis. In mammals, several amino acids must be obtained from the diet, creating a metabolic dependency that becomes particularly limiting in nutrient-restricted environments such as the tumor microenvironment. This limitation can impair immune cell function and reduce the effectiveness of cancer therapies. To address this challenge, we leverage advanced synthetic biology tools to enhance metabolic autonomy in mammalian cells and extend this approach to in vivo systems to investigate immune cell performance, with potential implications for improving cancer immunotherapy.

Collectively, this work demonstrates the cross-kingdom expansion of SME from microbial factories to mammalian cell therapies, laying a foundation for next-generation cancer immunotherapies, bacterial drug delivery, and future life-support systems for long-duration spaceflight.