J Integr Plant Biol. ›› 2023, Vol. 65 ›› Issue (6): 1442-1466.DOI: 10.1111/jipb.13469

• Functional Omics and Systems Biology • Previous Articles     Next Articles

Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites

Irene Julca1, Daniela Mutwil-Anderwald1, Vaishnervi Manoj1, Zahra Khan1, Soak Kuan Lai1, Lay K. Yang2, Ing T. Beh1, Jerzy Dziekan1, Yoon P. Lim3, Shen K. Lim1,3, Yee W. Low4, Yuen I. Lam1, Seth Tjia1, Yuguang Mu1, Qiao W. Tan1, Przemyslaw Nuc5, Le M. Choo4, Gillian Khew1,4, Loo Shining1, Antony Kam1, James P. Tam1, Zbynek Bozdech1, Maximilian Schmidt6, Bjoern Usadel6, Yoganathan Kanagasundaram2, Saleh Alseekh7,8, Alisdair Fernie7,8, Hoi Y. Li1 and Marek Mutwil1*   

  1. 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. Singapore Botanic Gardens, Singapore 259569, Singapore
    5. Department of Gene Expression, Faculty of Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan 61-614, Poland
    6. IBG-4 Bioinformatics, Forschungszentrum Jülich, Jülich 52428, Germany
    7. Max-Planck-Institut für Molekulare Pflanzenphysiologie, Potsdam-Golm 14476, Germany
    8. Center of Plant Systems Biology and Biotechnology, Plovdiv 4000, Bulgaria
    *Correspondence:Marek Mutwi(mutwil@ntu.edu.sg)
  • Received:2022-07-13 Accepted:2023-02-18 Online:2023-02-21 Published:2023-06-01

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.

Key words: genome, medicinal, metabolomics, mode of action, transcriptome

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