{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T21:37:08Z","timestamp":1779313028558,"version":"3.51.4"},"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/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":["81403038"],"award-info":[{"award-number":["81403038"]}],"id":[{"id":"10.13039\/100014718","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Salvia miltiorrhiza<\/jats:italic> is a model plant for Chinese herbal medicine with significant pharmacologic effects due to its tanshinone components. Our previous study indicated that nitrogen starvation stress increased its tanshinone content. However, the molecular mechanism of this low nitrogen-induced tanshinone biosynthesis is still unclear. Thus, this study aimed to elucidate the molecular mechanism of tanshinone biosynthesis in <jats:italic>S<\/jats:italic>. <jats:italic>miltiorrhiza<\/jats:italic> under different N conditions [N-free (N0), low-N (Nl), and full-N (Nf, as control) conditions] by using transcriptome and metabolome analyses. Our results showed 3,437 and 2,274 differentially expressed unigenes between N0 and Nf as well as Nl and Nf root samples, respectively. N starvation (N0 and Nl) promoted the expression of the genes involved in the MVA and MEP pathway of tanshinone and terpenoid backbone biosynthesis. Gene ontology and KEGG analyses revealed that terpenoid backbone biosynthesis, hormone signal transduction, and phenylpropanoid biosynthesis were promoted under N starvation conditions, whereas starch and sucrose metabolisms, nitrogen and phosphorus metabolisms, as well as membrane development were inhibited. Furthermore, metabolome analysis showed that metabolite compounds and biosynthesis of secondary metabolites were upregulated. This study provided a novel insight into the molecular mechanisms of tanshinone production in <jats:italic>S<\/jats:italic>. <jats:italic>miltiorrhiza<\/jats:italic> in response to nitrogen stress.<\/jats:p>","DOI":"10.1371\/journal.pone.0273495","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T17:40:16Z","timestamp":1661449216000},"page":"e0273495","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Integrative transcriptomic and metabolomic analyses unveil tanshinone biosynthesis in Salvia miltiorrhiza root under N starvation stress"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4317-0029","authenticated-orcid":true,"given":"Li-Lan","family":"Lu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Xiu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Fang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"pone.0273495.ref001","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1177\/0091270005282630","article-title":"Danshen: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use","volume":"45","author":"L Zhou","year":"2005","journal-title":"J Clin Pharm"},{"issue":"1","key":"pone.0273495.ref002","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1002\/med.20077","article-title":"New developments in the chemistry and biology of the bioactive constituents of Tanshen","volume":"27","author":"X Wang","year":"2007","journal-title":"Med Res Rev"},{"key":"pone.0273495.ref003","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1007\/s11033-007-9130-2","article-title":"Characterization and expression profiling of tyrosine aminotransferase gene from Salvia miltiorrhiza (Dan-shen) in rosmarinic acid biosynthesis pathway","volume":"35","author":"B Huang","year":"2008","journal-title":"Mol Biol Rep"},{"key":"pone.0273495.ref004","doi-asserted-by":"crossref","first-page":"e29713","DOI":"10.1371\/journal.pone.0029713","article-title":"The c4h, tat, hppr and hppd genes prompted engineering of rosmarinic acid biosynthetic pathway in Salvia miltiorrhiza hairy root cultures","volume":"6","author":"Y Xiao","year":"2011","journal-title":"PLoS One"},{"issue":"11","key":"pone.0273495.ref005","doi-asserted-by":"crossref","first-page":"1941","DOI":"10.1016\/j.chroma.2008.12.032","article-title":"Advancement in analysis of Salviae miltiorrhizae Radix et Rhizoma (Danshen)","volume":"1216","author":"YG Li","year":"2009","journal-title":"J Chrom A"},{"key":"pone.0273495.ref006","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.lfs.2008.08.003","article-title":"Tanshinone IIA reduces macrophage death induced by hydrogen peroxide by upregulating glutathione peroxidase","volume":"83","author":"YI Li","year":"2008","journal-title":"Life Sci"},{"issue":"7378","key":"pone.0273495.ref007","doi-asserted-by":"crossref","first-page":"S90","DOI":"10.1038\/480S90a","article-title":"Modernization: One step at a time","volume":"480","author":"Z. 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