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

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.

Telomere-to-telomere genome assembly ofOldenlandia diffusa

“… 19 Genomic studies on O. corymbosa have identified two genes responsible for ursolic acid synthesis and its interaction with cancer cells. 20 Meanwhile, the more widely researched O. diffusa still lacks a high-quality genome sequence, which impedes research into its bioactive components and molecular studies.…”

Genetic diversity of Coffea arabica L. mitochondrial genomes caused by repeat- mediated recombination and RNA editing

“…The Neolamarckia cadamba mitochondrial genome not only revealed its phylogenetic position within the Gentianales order but also shed light on its taxonomic relationship within the Rubiaceae family ( Wang et al., 2021 ). Oldenlandia corymbosa’s smaller mitochondrial genome size compared to other family members indicates variations in size and content within the Rubiaceae species ( Julca et al., 2023 ). The intricacies of the Psychotria viridis mitochondrial genome, presented through multiple mitogenome structures and evidence of heteroplasmy, enrich our understanding of mitochondrial genome organization ( Varani et al., 2022 ).…”

Transcriptomic and metabolomic characterization of antibacterial activity of Melastoma dodecandrum

“…Multi-omics methods, consisting of a combination of transcriptomics, metabolomics, genomics and/or proteomics, have been utilized in the drug discovery process and have been recognized as a useful tool to identify new targets and the mechanisms of lead compounds ( Goff et al., 2020 ). The multi-omics strategy may also be used to discover plant metabolic genes and pathways using co-expression analysis and metabolite-based genome-wide association studies ( Zhan et al., 2022 ; Zhao and Rhee, 2022 ; Julca et al ; Usadel et al., 2009 ; Lim et al., 2022 ). Taken together, such multi-omics approaches may represent the means to address challenges associated with bioprospecting and bridge the knowledge gap.…”