As part of the UM Natural Product Discovery Initiative, the Kersten lab aims to discover new plant-based chemicals to cure human diseases.
For millennia, humans have explored the plant kingdom for ways to ease pain, treat injuries, and cure disease. Ancient herbal medicines derived from botanical exploration are based on the activity of small chemicals called plant natural products, many of which have been developed in the last two centuries into therapeutic drugs to cure cancer and infectious diseases, and ameliorate pain. In the Kersten Lab, plant natural products are the inspiration for discovering new chemical solutions to treat human diseases. We use a combination of activity-guided discovery (herbal medicinal knowledge) and a gene-guided approach (plant genome mining) to discover new plant chemistry with therapeutic potential. Our goal is to overcome three bottlenecks in natural product drug discovery and development:
- Rediscovery of known chemistry,
- Scaled production of lead structures in a sustainable, source-plant-independent fashion,
- Diversification of lead structures for bioactivity optimization.
Our analytical toolbox includes bioinformatics, mass spectrometry-based metabolomics and proteomics, synthetic biology and analytical chemistry to address these challenges and to develop plant natural product-based libraries for pharmaceutical evaluation.
Development of gene-guided approaches for plant natural product drug discovery
Elucidation of plant natural product biosynthesis
Development of synthetic biology approaches for diversification and pharmaceutical evaluation of plant natural products
Mass spectrometry-based identification of specialized metabolites
Evolution of plant specialized metabolism
Kersten, R.D., Weng, J.-K. Gene-guided discovery and engineering of branched cyclic peptides in plants. Proc. Natl. Acad. Sci. U. S. A. 115, E10961-E10969 (2018).
Kersten, R.D.*, Lee, S.*, Fujita, D. Pluskal, T., Kram, S., Smith, J.E., Iwai, T., Noel, J.P., Fujita, M., Weng, J.-K. A Red Algal Bourbonane Sesquiterpene Synthase Defined by Microgram-scale NMR-coupled Crystalline Sponge XRD Analysis. J. Am. Chem. Soc. 139, 16838-16844 (2017).
Kersten, R.D., Ziemert, N., Gonzalez, D.J., Duggan, B.M., Nizet, V., Dorrestein, P.C., Moore, B.S. Glycogenomics as a mass spectrometry-guided genome-mining method for microbial glycosylated molecules. Proc. Natl. Acad. Sci. U. S. A. 110, E4407-4416 (2013).
Xu, Y.*, Kersten, R.D.*, Nam, S.J., Lu, L., Al-Suwailem, A.M., Zheng, H., Fenical, W., Dorrestein, P.C., Moore, B.S., Qian, P.Y. Bacterial biosynthesis and maturation of the didemnin anti-cancer agents. J. Am. Chem. Soc. 134, 8625-32 (2012).
Kersten, R.D., Yang, Y.L., Xu, Y., Cimermancic, P., Nam, S.J., Fenical, W., Fischbach, M.A., Moore, B.S., Dorrestein, P.C. A mass spectrometry-guided genome mining approach for natural product peptidogenomics. Nat. Chem. Biol. 7, 794-802 (2011).