Jie Li

Our research focuses on microbe-derived natural product-based drug discovery. Natural products are specialized metabolites produced by living organisms such as microbes. With evolutionarily optimized chemical structures and intrinsic biological activities, natural products continue to be one of the most important sources for drug discovery, as exemplified by the first true antibiotic penicillin and a first-line anticancer drug doxorubicin among many other clinically used drugs. Microbes harbor biosynthetic genes to encode enzymes that catalyze various chemical reactions to generate unique molecules. The chemical diversity and biological activity of these small molecules is virtually limitless by virtue of the abundant microbial biodiversity and continued evolution that they can access. We focus on translating this vast chemical and biological potential into opportunities for drug discovery. Our research approach is based on the opportunities that 1) a large number of unique microbial small molecules still await discovery, especially from underexplored microorganisms; 2) the exponential growth in microbial (meta)genomic data can facilitate the rapid identification of the biosynthetic genes that encode small molecules; and 3) harnessing these biosynthetic genes can enable the construction of small molecules in the laboratory. We are particularly interested in small molecules produced by human microbiota, a community of microbes that live in and on human bodies. These microbes have evolved a symbiotic relationship with humans, and their metabolites directly interact with human cells, leading to intrinsic and profound impacts on human health. We integrate multidisciplinary approaches, including informatics, metabolomics, and biochemistry, to discover these specialized metabolites and elucidate their functions in human health.

Xue, D.; Zou, H.; Qiu, Y.; Lv, W.; Madden, M. D.; Lian, X.; Xu, M.; Pulliam, C.; Older, E. A.; Campbell, A.; der Rond, T.; Awakawa, T.; Yuan, C.; Moore, B. S.; Li, J. Discovery of acylsulfenic acid-featuring natural product sulfenicin and characterization of its biosynthesis. Nature Chemistry, 2025, DOI: 10.1038/s41557-025-01833-9 Older, E. A.; Mitchell, M.; Campbell, A.; Lian, X.; Madden, M.; Wang, Y.; VanderVeen, B.; Tatum, R.; Murphy, E. A.; Chen, Y.; Fan, D.; Ellermann, M.; Li, J. Human gut commensal Alistipes timonensis modulates the host lipidome and delivers anti-inflammatory outer membrane vesicles to suppress colitis in an Il10-deficient mouse model. Gut Microbes, 2025, 17(1), DOI: 10.1080/19490976.2025.2517380. Xue, D.; Wu, Q.; Hou L.; Pulliam, C.; Xu, M.; Madden, M. D.; Madu, J.