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 o...
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| Veröffentlicht in: | Journal of integrative plant biology 2023-06, Vol.65 (6), p.1442-1466 |
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| creator | Julca, Irene Mutwil‐Anderwald, Daniela Manoj, Vaishnervi Khan, Zahra Lai, Soak Kuan Yang, Lay K. Beh, Ing T. Dziekan, Jerzy Lim, Yoon P. Lim, Shen K. Low, Yee W. Lam, Yuen I. Tjia, Seth Mu, Yuguang Tan, Qiao W. Nuc, Przemyslaw Choo, Le M. Khew, Gillian Shining, Loo Kam, Antony Tam, James P. Bozdech, Zbynek Schmidt, Maximilian Usadel, Bjoern Kanagasundaram, Yoganathan Alseekh, Saleh Fernie, Alisdair Li, Hoi Y. Mutwil, Marek |
| description | 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.
Traditional Chinese medicine uses Oldenlandia corymbosa against several forms of cancer. O. orymbose contains ursolic acid (UA), which causes mitotic catastrophe, and CETSA‐MS and molecular docking identified several high‐confidence protein targets of UA. Moreover, genome sequencing and analysis of O. corymbosa identified the genes involved in UA biosynthesis. |
| doi_str_mv | 10.1111/jipb.13469 |
| format | Article |
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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.
Traditional Chinese medicine uses Oldenlandia corymbosa against several forms of cancer. O. orymbose contains ursolic acid (UA), which causes mitotic catastrophe, and CETSA‐MS and molecular docking identified several high‐confidence protein targets of UA. Moreover, genome sequencing and analysis of O. corymbosa identified the genes involved in UA biosynthesis.</description><identifier>ISSN: 1672-9072</identifier><identifier>EISSN: 1744-7909</identifier><identifier>DOI: 10.1111/jipb.13469</identifier><identifier>PMID: 36807520</identifier><language>eng</language><publisher>China (Republic : 1949- ): Wiley Subscription Services, Inc</publisher><subject>Acids ; Biosynthesis ; Cancer ; Gene expression ; genome ; Genomics ; medicinal ; Metabolites ; Metabolomics ; Mode of action ; Natural resources ; Oldenlandia - chemistry ; Oldenlandia corymbosa ; Secondary metabolites ; Transcriptome ; Transcriptomics ; Tumor cell lines ; Ursolic Acid</subject><ispartof>Journal of integrative plant biology, 2023-06, Vol.65 (6), p.1442-1466</ispartof><rights>2023 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.</rights><rights>2023 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4239-eb06bb6f6181c776c036632a7ba398116deeca7e4cbf1009f870ae46e461083e3</citedby><cites>FETCH-LOGICAL-c4239-eb06bb6f6181c776c036632a7ba398116deeca7e4cbf1009f870ae46e461083e3</cites><orcidid>0000-0001-6946-5576 ; 0000-0002-7848-0126 ; 0000-0001-5690-7478 ; 0000-0002-1332-7948</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.wanfangdata.com.cn/images/PeriodicalImages/zwxb/zwxb.jpg</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fjipb.13469$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fjipb.13469$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36807520$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Julca, Irene</creatorcontrib><creatorcontrib>Mutwil‐Anderwald, Daniela</creatorcontrib><creatorcontrib>Manoj, Vaishnervi</creatorcontrib><creatorcontrib>Khan, Zahra</creatorcontrib><creatorcontrib>Lai, Soak Kuan</creatorcontrib><creatorcontrib>Yang, Lay K.</creatorcontrib><creatorcontrib>Beh, Ing T.</creatorcontrib><creatorcontrib>Dziekan, Jerzy</creatorcontrib><creatorcontrib>Lim, Yoon P.</creatorcontrib><creatorcontrib>Lim, Shen K.</creatorcontrib><creatorcontrib>Low, Yee W.</creatorcontrib><creatorcontrib>Lam, Yuen I.</creatorcontrib><creatorcontrib>Tjia, Seth</creatorcontrib><creatorcontrib>Mu, Yuguang</creatorcontrib><creatorcontrib>Tan, Qiao W.</creatorcontrib><creatorcontrib>Nuc, Przemyslaw</creatorcontrib><creatorcontrib>Choo, Le M.</creatorcontrib><creatorcontrib>Khew, Gillian</creatorcontrib><creatorcontrib>Shining, Loo</creatorcontrib><creatorcontrib>Kam, Antony</creatorcontrib><creatorcontrib>Tam, James P.</creatorcontrib><creatorcontrib>Bozdech, Zbynek</creatorcontrib><creatorcontrib>Schmidt, Maximilian</creatorcontrib><creatorcontrib>Usadel, Bjoern</creatorcontrib><creatorcontrib>Kanagasundaram, Yoganathan</creatorcontrib><creatorcontrib>Alseekh, Saleh</creatorcontrib><creatorcontrib>Fernie, Alisdair</creatorcontrib><creatorcontrib>Li, Hoi Y.</creatorcontrib><creatorcontrib>Mutwil, Marek</creatorcontrib><title>Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti‐cancer metabolites</title><title>Journal of integrative plant biology</title><addtitle>J Integr Plant Biol</addtitle><description>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.
Traditional Chinese medicine uses Oldenlandia corymbosa against several forms of cancer. O. orymbose contains ursolic acid (UA), which causes mitotic catastrophe, and CETSA‐MS and molecular docking identified several high‐confidence protein targets of UA. Moreover, genome sequencing and analysis of O. corymbosa identified the genes involved in UA biosynthesis.</description><subject>Acids</subject><subject>Biosynthesis</subject><subject>Cancer</subject><subject>Gene expression</subject><subject>genome</subject><subject>Genomics</subject><subject>medicinal</subject><subject>Metabolites</subject><subject>Metabolomics</subject><subject>Mode of action</subject><subject>Natural resources</subject><subject>Oldenlandia - chemistry</subject><subject>Oldenlandia corymbosa</subject><subject>Secondary metabolites</subject><subject>Transcriptome</subject><subject>Transcriptomics</subject><subject>Tumor cell lines</subject><subject>Ursolic Acid</subject><issn>1672-9072</issn><issn>1744-7909</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp9kcFu1DAQhi0Eou3ChQdAkRBShUgZ26mdHEsFpahSOcDZsp0JeJXYi52lhBOPgMQb8iQ4m20PHLAs-R_rm98a_4Q8oXBC83q1dhtzQnklmnvkkMqqKmUDzf2shWRlA5IdkKOU1gC8BsEekgMuapCnDA7J7wv0YXD2ZTFG7ZONbjMutfZtMeCoTejni1zrfkouFaErrvsWfZ8Jpwsb4jSYkHQR8RvqPhXjFyyMC2nyWc0dO6vQ4tyq7eiC3yk_uj8_f1ntLcbbp9yI6RF50GUffLw_V-TT2zcfz9-VV9cXl-dnV6WtGG9KNCCMEZ2gNbVSCgtcCM60NJo3NaWiRbRaYmVNRwGarpagsRJ5U6g58hV5vvjeaN9p_1mtwzbmKZP6cfPdMGAcBGRyRY4XbhPD1y2mUQ0uWezzB2DYJsWkrBspuTzN6LN_0DtPVjMpKAfKMvVioWwMKUXs1Ca6QcdJUVBzpGqOVO0izfDTveXWDNjeobcZZoDux3A9Tv-xUu8vP7xeTP8CDzOuTw</recordid><startdate>202306</startdate><enddate>202306</enddate><creator>Julca, Irene</creator><creator>Mutwil‐Anderwald, Daniela</creator><creator>Manoj, Vaishnervi</creator><creator>Khan, Zahra</creator><creator>Lai, Soak Kuan</creator><creator>Yang, Lay K.</creator><creator>Beh, Ing T.</creator><creator>Dziekan, Jerzy</creator><creator>Lim, Yoon P.</creator><creator>Lim, Shen K.</creator><creator>Low, Yee W.</creator><creator>Lam, Yuen I.</creator><creator>Tjia, Seth</creator><creator>Mu, Yuguang</creator><creator>Tan, Qiao W.</creator><creator>Nuc, Przemyslaw</creator><creator>Choo, Le M.</creator><creator>Khew, Gillian</creator><creator>Shining, Loo</creator><creator>Kam, Antony</creator><creator>Tam, James P.</creator><creator>Bozdech, Zbynek</creator><creator>Schmidt, Maximilian</creator><creator>Usadel, Bjoern</creator><creator>Kanagasundaram, Yoganathan</creator><creator>Alseekh, Saleh</creator><creator>Fernie, Alisdair</creator><creator>Li, Hoi Y.</creator><creator>Mutwil, Marek</creator><general>Wiley Subscription Services, Inc</general><general>Department of Biochemistry,National University of Singapore,Singapore 117596,Singapore%Singapore Botanic Gardens,Singapore 259569,Singapore%Department of Gene Expression,Faculty of Biology,Institute of Molecular Biology and Biotechnology,Adam Mickiewicz University,Poznan 61-614,Poland%School of Biological Sciences,Nanyang Technological University,Singapore 639798,Singapore</general><general>School of Biological Sciences,Nanyang Technological University,Singapore 639798,Singapore%Shared Analytics,Singapore Institute of Food and Biotechnology Innovation(SIFBI),Agency for Science,Technology and Research(ASTAR),Singapore 138671,Singapore%Department of Biochemistry,National University of Singapore,Singapore 117596,Singapore%School of Biological Sciences,Nanyang Technological University,Singapore 639798,Singapore</general><general>Singapore Botanic Gardens,Singapore 259569,Singapore%IBG-4 Bioinformatics,Forschungszentrum Jülich,Jülich 52428,Germany%Max-Planck-Institut für Molekulare Pflanzenphysiologie,Potsdam-Golm 14476,Germany</general><general>Center of Plant Systems Biology and Biotechnology,Plovdiv 4000,Bulgaria</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope><orcidid>https://orcid.org/0000-0001-6946-5576</orcidid><orcidid>https://orcid.org/0000-0002-7848-0126</orcidid><orcidid>https://orcid.org/0000-0001-5690-7478</orcidid><orcidid>https://orcid.org/0000-0002-1332-7948</orcidid></search><sort><creationdate>202306</creationdate><title>Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti‐cancer metabolites</title><author>Julca, Irene ; Mutwil‐Anderwald, Daniela ; Manoj, Vaishnervi ; Khan, Zahra ; Lai, Soak Kuan ; Yang, Lay K. ; Beh, 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T.</au><au>Dziekan, Jerzy</au><au>Lim, Yoon P.</au><au>Lim, Shen K.</au><au>Low, Yee W.</au><au>Lam, Yuen I.</au><au>Tjia, Seth</au><au>Mu, Yuguang</au><au>Tan, Qiao W.</au><au>Nuc, Przemyslaw</au><au>Choo, Le M.</au><au>Khew, Gillian</au><au>Shining, Loo</au><au>Kam, Antony</au><au>Tam, James P.</au><au>Bozdech, Zbynek</au><au>Schmidt, Maximilian</au><au>Usadel, Bjoern</au><au>Kanagasundaram, Yoganathan</au><au>Alseekh, Saleh</au><au>Fernie, Alisdair</au><au>Li, Hoi Y.</au><au>Mutwil, Marek</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti‐cancer metabolites</atitle><jtitle>Journal of integrative plant biology</jtitle><addtitle>J Integr Plant Biol</addtitle><date>2023-06</date><risdate>2023</risdate><volume>65</volume><issue>6</issue><spage>1442</spage><epage>1466</epage><pages>1442-1466</pages><issn>1672-9072</issn><eissn>1744-7909</eissn><abstract>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.
Traditional Chinese medicine uses Oldenlandia corymbosa against several forms of cancer. O. orymbose contains ursolic acid (UA), which causes mitotic catastrophe, and CETSA‐MS and molecular docking identified several high‐confidence protein targets of UA. Moreover, genome sequencing and analysis of O. corymbosa identified the genes involved in UA biosynthesis.</abstract><cop>China (Republic : 1949- )</cop><pub>Wiley Subscription Services, Inc</pub><pmid>36807520</pmid><doi>10.1111/jipb.13469</doi><tpages>25</tpages><orcidid>https://orcid.org/0000-0001-6946-5576</orcidid><orcidid>https://orcid.org/0000-0002-7848-0126</orcidid><orcidid>https://orcid.org/0000-0001-5690-7478</orcidid><orcidid>https://orcid.org/0000-0002-1332-7948</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1672-9072 |
| ispartof | Journal of integrative plant biology, 2023-06, Vol.65 (6), p.1442-1466 |
| issn | 1672-9072 1744-7909 |
| language | eng |
| recordid | cdi_wanfang_journals_zwxb202306008 |
| source | Wiley-Blackwell Journals; MEDLINE; Alma/SFX Local Collection |
| subjects | Acids Biosynthesis Cancer Gene expression genome Genomics medicinal Metabolites Metabolomics Mode of action Natural resources Oldenlandia - chemistry Oldenlandia corymbosa Secondary metabolites Transcriptome Transcriptomics Tumor cell lines Ursolic Acid |
| title | Genomic, transcriptomic, and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti‐cancer metabolites |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-01T10%3A52%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-wanfang_jour_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Genomic,%20transcriptomic,%20and%20metabolomic%20analysis%20of%20Oldenlandia%20corymbosa%20reveals%20the%20biosynthesis%20and%20mode%20of%20action%20of%20anti%E2%80%90cancer%20metabolites&rft.jtitle=Journal%20of%20integrative%20plant%20biology&rft.au=Julca,%20Irene&rft.date=2023-06&rft.volume=65&rft.issue=6&rft.spage=1442&rft.epage=1466&rft.pages=1442-1466&rft.issn=1672-9072&rft.eissn=1744-7909&rft_id=info:doi/10.1111/jipb.13469&rft_dat=%3Cwanfang_jour_proqu%3Ezwxb202306008%3C/wanfang_jour_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2827613012&rft_id=info:pmid/36807520&rft_wanfj_id=zwxb202306008&rfr_iscdi=true |