{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:07:30Z","timestamp":1789106850360,"version":"build-2803163510"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014718","name":"Innovative Research Group Project of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82574543, 81173486"],"award-info":[{"award-number":["82574543, 81173486"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006407","name":"Natural Science Foundation of Henan Province","doi-asserted-by":"publisher","award":["252300423157, 232301420078"],"award-info":[{"award-number":["252300423157, 232301420078"]}],"id":[{"id":"10.13039\/501100006407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Plant Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Isodon rubescens<\/jats:italic>\n                      f. lushanensis, a typical form of\n                      <jats:italic>I. rubescens<\/jats:italic>\n                      , is characterized by its natural deficiency in oridonin and the presence of a unique ent-kaurane diterpenoid, lushanrubescensin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To elucidate the molecular basis underlying the distinct chemical profiles between\n                      <jats:italic>I. rubescens<\/jats:italic>\n                      f. lushanensis and\n                      <jats:italic>I. rubescens<\/jats:italic>\n                      (Hemsl.) Hara, we conducted a comprehensive analysis utilizing high-quality genomic and transcriptomic data of\n                      <jats:italic>I. rubescens<\/jats:italic>\n                      f. lushanensis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Through a genome-wide survey, our study identified 83 terpene synthase (\n                      <jats:italic>TPS<\/jats:italic>\n                      ) genes, including 13\n                      <jats:italic>TPS<\/jats:italic>\n                      -C and 9\n                      <jats:italic>TPS-e<\/jats:italic>\n                      \/f subfamily genes, which are implicated in diterpenoid biosynthesis. By integrating conserved motif analysis, differential expression profiling (FPKM), and RT-qPCR validation, we successfully screened key candidate genes. Subsequent heterologous expression in\n                      <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                      enabled the functional characterization of five diterpene synthase genes, specifically CPS and KSL enzymes, involved in the central modules of diterpenoid synthesis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These findings not only expand the repertoire of known biosynthetic genes in\n                      <jats:italic>I. rubescens<\/jats:italic>\n                      but also offer valuable insights into the divergent biosynthetic pathways of oridonin and lushanrubescensin, paving the way for future metabolic engineering and synthetic biology studies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fpls.2026.1937259","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:30:30Z","timestamp":1789104630000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genome-wide analysis of TPS family reveals kaurene synthase-like genes in Isodon rubescens f. lushanensis"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Yang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan","place":["Hangzhou, China"]},{"name":"Co-Construction Collaborative Innovation Centre for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of China, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conglong","family":"Lian","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan","place":["Hangzhou, China"]},{"name":"Co-Construction Collaborative Innovation Centre for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of China, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Zhejiang","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Zhejiang","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuyu","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Xue","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan","place":["Hangzhou, China"]},{"name":"Co-Construction Collaborative Innovation Centre for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of China, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoya","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan","place":["Hangzhou, China"]},{"name":"Co-Construction Collaborative Innovation Centre for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of China, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lipeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfan","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Fu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lidan","family":"Ye","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Zhejiang","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suiqing","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan Key Laboratory of Chinese Medicine Resources and Chemistry, Henan University of Chinese Medicine, Henan","place":["Zhengzhou, China"]},{"name":"Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Henan","place":["Hangzhou, China"]},{"name":"Co-Construction Collaborative Innovation Centre for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of China, Henan","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2417","DOI":"10.1002\/prot.22751","article-title":"Diterpene cyclases and the nature of the isoprene fold","volume":"78","author":"Cao","year":"2010","journal-title":"Proteins"},{"key":"B2","doi-asserted-by":"publisher","first-page":"122","DOI":"10.13422\/j.cnki.syfjx.2011.17.052","article-title":"Qualitative evaluation of Rabdosiae rubescentis herba from different place and origin","volume":"17","author":"Chen","year":"2011","journal-title":"Chin. J. Exp. Tradit. Med. Formulae"},{"key":"B3","first-page":"5","article-title":"Molecular analysis of different origin of Rabdosia rubescens germplasm resources","volume":"12","author":"Chen","year":"2016","journal-title":"Asia Pac. Tradit. Med."},{"key":"B4","first-page":"15","article-title":"New taxa of Rabdosia rubescens","volume":"24","author":"Gao","year":"1986","journal-title":"J. Syst. Evol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"269","DOI":"10.3987\/com-02-9688","article-title":"Ent-kaurane diterpenoids from Isodon rubescens var. lushanensis","volume":"51","author":"Han","year":"2003","journal-title":"Chem. Pharm. Bull."},{"key":"B6","doi-asserted-by":"publisher","first-page":"6175","DOI":"10.1016\/j.febslet.2006.10.018","article-title":"Identification and functional analysis of bifunctional ent-kaurene synthase from the moss Physcomitrella patens","volume":"580","author":"Hayashi","year":"2006","journal-title":"FEBS Lett."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1111\/j.1365-313X.2011.04756.x","article-title":"Domain loss has independently occurred multiple times in plant terpene synthase evolution","volume":"68","author":"Hillwig","year":"2011","journal-title":"Plant J."},{"key":"B8","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1007\/s11427-018-9472-y","article-title":"Herbgenomics: a stepping stone for research into herbal medicine","volume":"62","author":"Hu","year":"2019","journal-title":"Sci. China Life Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/gbe\/evz142","article-title":"A comprehensive survey on the terpene synthase gene family provides new insight into its evolutionary patterns","volume":"11","author":"Jiang","year":"2019","journal-title":"Genome Biol. Evol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1104\/pp.17.00202","article-title":"Functional diversification of kaurene synthase-like genes in Isodon rubescens","volume":"174","author":"Jin","year":"2017","journal-title":"Plant Physiol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0266546","article-title":"Comparative analysis of chloroplast genomes reveals phylogenetic relationships and intraspecific variation in the medicinal plant Isodon rubescens","volume":"17","author":"Lian","year":"2022","journal-title":"PloS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12870-025-07460-3","article-title":"Multi-combination comparative transcriptome analysis response to MeJA and identifies genes putatively involved in oridonin biosynthesis in Isodon rubescens","volume":"25","author":"Lian","year":"2025","journal-title":"BMC Plant Biol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.70322\/sbe.2026.10006","article-title":"Emerging technologies empowering the biosynthesis of paclitaxel","volume":"4","author":"Liu","year":"2026","journal-title":"Synth. Biol. Eng."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232314652","article-title":"Molecular docking and dynamics simulation revealed the potential inhibitory activity of new drugs against human topoisomerase I receptor","volume":"23","author":"Madeddu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/nmeth.1226","article-title":"Mapping and quantifying mammalian transcriptomes by RNA-Seq","volume":"5","author":"Mortazavi","year":"2008","journal-title":"Nat. Methods"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pone.0176507","article-title":"Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases","volume":"12","author":"Pelot","year":"2017","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/elsc.70018","article-title":"Engineering caffeic acid O-methyltransferase for efficient de novo ferulic acid synthesis","volume":"25","author":"Shang","year":"2025","journal-title":"Eng. Life Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"14991","DOI":"10.1038\/s41598-017-15005-4","article-title":"Engineering Saccharomyces cerevisiae for geranylgeraniol overproduction by combinatorial design","volume":"7","author":"Song","year":"2017","journal-title":"Sci. Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/j.molp.2022.12.007","article-title":"A chromosome-level genome assembly reveals that tandem-duplicated CYP706V oxidase genes control oridonin biosynthesis in the shoot apex of Isodon rubescens","volume":"16","author":"Sun","year":"2023","journal-title":"Mol. Plant"},{"key":"B20","doi-asserted-by":"publisher","first-page":"372","DOI":"10.13705\/j.issn.1671-6825.1987.04.012","article-title":"Study of the antitumor action of lushanrubescensin","volume":"22","author":"Wang","year":"1987","journal-title":"Henan Inst. Med. Sci."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.70322\/sbe.2026.10009","article-title":"Advances in gastrodin production: from native to engineered biosynthesis","volume":"4","author":"Wang","year":"2026","journal-title":"Synth. Biol. Eng."},{"key":"B22","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1016\/j.molp.2023.04.012","article-title":"Dynamic evolution of terpenoid biosynthesis in the Lamiaceae","volume":"16","author":"Wang","year":"2023","journal-title":"Mol. Plant"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2--a multiple sequence alignment editor and analysis workbench","volume":"25","author":"Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1002\/bit.25002","article-title":"Construction of a controllable beta-carotene biosynthetic pathway by decentralized assembly strategy in Saccharomyces cerevisiae","volume":"111","author":"Xie","year":"2014","journal-title":"Biotechnol. Bioeng."},{"key":"B25","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.ymben.2014.11.007","article-title":"Sequential control of biosynthetic pathways for balanced utilization of metabolic intermediates in Saccharomyces cerevisiae","volume":"28","author":"Xie","year":"2015","journal-title":"Metab. Eng."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giae075","article-title":"High-quality assembly of the T2T genome for Isodon rubescens f. lushanensis reveals genomic structure variations between 2 typical forms of Isodon rubescens","volume":"13","author":"Yang","year":"2024","journal-title":"GigaScience"},{"key":"B26","doi-asserted-by":"publisher","first-page":"506","DOI":"10.12677\/tcm.2020.96076","article-title":"Current situation and prospective on resource evaluation and sustainable utilization of Rabdosiae rubescentis Herba","volume":"9","author":"Yang","year":"2020","journal-title":"Tradit. Chin. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"241","DOI":"10.14146\/j.cnki.cjp.2007.05.015","article-title":"Freeze-drying of oridonin-loaded solid lipid nanoparticles","volume":"5","author":"Zhao","year":"2007","journal-title":"Chin. J. Pharm."}],"container-title":["Frontiers in Plant Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2026.1937259\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:30:35Z","timestamp":1789104635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpls.2026.1937259\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":28,"alternative-id":["10.3389\/fpls.2026.1937259"],"URL":"https:\/\/doi.org\/10.3389\/fpls.2026.1937259","relation":{},"ISSN":["1664-462X"],"issn-type":[{"value":"1664-462X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]},"article-number":"1937259"}}