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. 2023 Jun;65(6):1442-1466.
doi: 10.1111/jipb.13469. Epub 2023 Apr 4.

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

Irene Julca  1 , Daniela Mutwil-Anderwald  1 , Vaishnervi Manoj  1 , Zahra Khan  1 , Soak Kuan Lai  1 , Lay K Yang  2 , Ing T Beh  1 , Jerzy Dziekan  1 , Yoon P Lim  3 , Shen K Lim  1   3 , Yee W Low  4 , Yuen I Lam  1 , Seth Tjia  1 , Yuguang Mu  1 , Qiao W Tan  1 , Przemyslaw Nuc  5 , Le M Choo  4 , Gillian Khew  1   4 , Loo Shining  1 , Antony Kam  1 , James P Tam  1 , Zbynek Bozdech  1 , Maximilian Schmidt  6 , Bjoern Usadel  6 , Yoganathan Kanagasundaram  2 , Saleh Alseekh  7   8 , Alisdair Fernie  7   8 , Hoi Y Li  1 , Marek Mutwil  1
Affiliations

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

Irene Julca et al. J Integr Plant Biol. 2023 Jun.

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.

Keywords: genome; medicinal; metabolomics; mode of action; transcriptome.

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