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Genomic,transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites |
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| Authors: | Irene Julca Daniela Mutwil-Anderwald Vaishnervi Manoj Zahra Khan Soak Kuan Lai Lay K. Yang Ing T. Beh Jerzy Dziekan Yoon P. Lim Shen K. Lim Yee W. Low Yuen I. Lam Seth Tjia Yuguang Mu Qiao W. Tan Przemyslaw Nuc Le M. Choo Gillian Khew Loo Shining Antony Kam James P. Tam Zbynek Bozdech Maximilian Schmidt Bjoern Usadel Yoganathan Kanagasundaram Saleh Alseekh Alisdair Fernie Hoi Y. Li Marek Mutwil |
| Affiliation: | 1. School of Biological Sciences, Nanyang Technological University, Singapore, 639798 Singapore;2. Shared Analytics, Singapore Institute of Food and Biotechnology Innovation (SIFBI), Agency for Science, Technology and Research (A*STAR), Singapore, 138671 Singapore;3. Department of Biochemistry, National University of Singapore, Singapore, 117596 Singapore;4. School of Biological Sciences, Nanyang Technological University, Singapore, 639798 Singapore Department of Biochemistry, National University of Singapore, Singapore, 117596 Singapore;5. Singapore Botanic Gardens, Singapore, 259569 Singapore;6. Department of Gene Expression, 7. Faculty of Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, 61-614 Poland;8. School of Biological Sciences, Nanyang Technological University, Singapore, 639798 Singapore Singapore Botanic Gardens, Singapore, 259569 Singapore;9. IBG-4 Bioinformatics, Forschungszentrum Jülich, Jülich, 52428 Germany;10. Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm, 14476 Germany Center of Plant Systems Biology and Biotechnology, Plovdiv, 4000 Bulgaria |
| Abstract: | 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. |
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