2 research outputs found
Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites
Plants accumulate a vast array of secondary metabolites, which constitute a natural resource for pharmaceuticals. Oldenlandia corymbosa belongs to the Rubiaceae family, and has been used in traditional medicine to treat different diseases, including cancer. However, the active metabolites of the plant, their biosynthetic pathway and mode of action in cancer are unknown. To fill these gaps, we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression, metabolic profiles, and anti-cancer activity. Our results show that O. corymbosa extracts are active against breast cancer cell lines and that ursolic acid is responsible for this activity. Moreover, we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic acid. Finally, we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay (CETSA) and reverse docking. Altogether, these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group, while the mode of action of ursolic acid will allow us to further develop this valuable compound.Ministry of Education (MOE)Nanyang Technological UniversityPublished versionI.J. is supported by Nanyang Biologics, M.M. is supported by a NTU StartâUp Grant and Singaporean Ministry of Education grant MOE2018âT2â2â053. J.M.D (NTUâPPFâ2019). Y.K. is supported by Natural Product Research Laboratory Biomedical Research Council of A*STAR (Agency for Science, Technology and Research) Transition Fund (H16/99/b0/004), the Singapore Institute of Food and Biotechnology Innovation core fund