{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:05:51Z","timestamp":1790877951507,"version":"4.1.0"},"reference-count":70,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of Jiangsu Food and Pharmaceutical Science College","award":["No. JSFPC2025007"],"award-info":[{"award-number":["No. JSFPC2025007"]}],"id":[{"id":"https:\/\/ror.org\/03ksbpa13","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n \n Eupatorium lindleyanum<\/jats:italic>\n is a medicinal plant rich in bioactive sesquiterpenoids, yet the genetic and regulatory basis underlying their biosynthesis remains completely unexplored. In particular, the marked tissue-specific accumulation of these compounds\u2014abundant in aerial organs but scarce in roots\u2014lacks a molecular explanation.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Here, we integrated UPLC-MS\/MS-based metabolomics with RNA-Seq transcriptomics to comprehensively profile sesquiterpenoid metabolites and their associated gene expression signatures across root, stem, leaf, and flower tissues of\n Eupatorium lindleyanum<\/jats:italic>\n . A total of 321 sesquiterpenoids were identified, exhibiting distinct tissue-specific accumulation patterns with highest abundance in flower, followed by leaf. Comparative analysis revealed 299 differentially accumulated sesquiterpenoid metabolites (DSMs), which were clustered into three major groups with preferential accumulation in leaf (Cluster 1), flower (Cluster 2), and root (Cluster 3). Transcriptome sequencing generated 99.43 Gb of clean data, yielding 147743 unigenes. Integration of metabolomic and transcriptomic datasets screened 20 structural genes (88 unigenes) involved in sesquiterpenoid biosynthesis, including MVA pathway genes (\n ACAT<\/jats:italic>\n ,\n HMGCS<\/jats:italic>\n ,\n HMGCR<\/jats:italic>\n ,\n MVK<\/jats:italic>\n ,\n PMK<\/jats:italic>\n ,\n MVD<\/jats:italic>\n ), MEP pathway genes (\n dxs<\/jats:italic>\n ,\n dxr<\/jats:italic>\n ,\n ispD<\/jats:italic>\n ,\n ispE<\/jats:italic>\n ,\n ispF<\/jats:italic>\n ,\n ispG<\/jats:italic>\n ,\n ispH<\/jats:italic>\n ), and downstream modification genes (\n FDPS<\/jats:italic>\n ,\n IDI<\/jats:italic>\n ,\n GAS<\/jats:italic>\n ,\n GDS<\/jats:italic>\n ,\n NES1<\/jats:italic>\n ,\n GAO<\/jats:italic>\n ,\n FLDH<\/jats:italic>\n ). Weighted gene co-expression network analysis (WGCNA) further prioritized hub genes within modules significantly correlated with key sesquiterpenoids. Additionally, five transcription factor families (\n AP2\/ERF<\/jats:italic>\n ,\n NAC<\/jats:italic>\n ,\n WRKY<\/jats:italic>\n ,\n MYB<\/jats:italic>\n , and\n bHLH<\/jats:italic>\n ) were identified as potential regulators based on strong correlations with DSMs accumulation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This study provides the first comprehensive view of tissue-specific sesquiterpenoid biosynthesis in\n Eupatorium lindleyanum<\/jats:italic>\n , establishing a prioritized set of candidate genes and regulators for functional validation. Our findings offer a foundational resource for metabolic engineering and molecular breeding aimed at enhancing the production of pharmacologically active sesquiterpenoids in this medicinal species.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0359566","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T17:29:11Z","timestamp":1790875751000},"page":"e0359566","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics integration reveals tissue-specific biosynthesis of sesquiterpenoids in the medicinal plant Eupatorium lindleyanum"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8782-1068","authenticated-orcid":true,"given":"Yingzhe","family":"Wang","sequence":"first","affiliation":[{"name":"Jiangsu Food and Pharmaceutical Science College","place":["Huaian, China"],"department":["School of Pharmacy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangsu Food and Pharmaceutical Science College","place":["Huaian, China"],"department":["School of Pharmacy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqiu","family":"Yuan","sequence":"additional","affiliation":[{"name":"Jiangsu Food and Pharmaceutical Science College","place":["Huaian, China"],"department":["School of Pharmacy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghan","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Traditional Chinese Medicine, Jilin Agricultural Science and Technology College","place":["Jilin City, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Food and Pharmaceutical Science College","place":["Huaian, China"],"department":["School of Pharmaceutical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Guo","sequence":"additional","affiliation":[{"name":"Jiangsu Food and Pharmaceutical Science College","place":["Huaian, China"],"department":["School of Pharmaceutical Engineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"issue":"3","key":"pone.0359566.ref001","doi-asserted-by":"crossref","first-page":"43","DOI":"10.5897\/JMPR2016.6313","article-title":"The genus Eupatorium L. 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