{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T10:34:49Z","timestamp":1788345289740,"version":"build-2803163510"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Salicylic acid (SA) and its methyl ester, methyl salicylate (MeSA) are well known inducers of local and systemic plant defense responses, respectively. MeSA is a major mediator of systemic acquired resistance (SAR) and its conversion back into SA is thought to be required for SAR. In many plant species, conversion of MeSA into SA is mediated by MeSA esterases of the SABP2 family. Here we show that the <jats:italic>Citrus sinensis<\/jats:italic> SABP2 homologue protein CsMES1 catalyzes the hydrolysis of MeSA into SA. Molecular modeling studies suggest that CsMES1 shares the same structure and SA-binding mode with tobacco SABP2. However, an amino acid polymorphism in the active site of CsMES1-related proteins suggested an important role in enzyme regulation. We present evidence that the side chain of this polymorphic residue directly influences enzyme activity and SA binding affinity in CsMES proteins. We also show that SA and CsMES1 transcripts preferentially accumulate during the incompatible interaction between <jats:italic>Xanthomonas aurantifolii<\/jats:italic> pathotype C and sweet orange plants. Moreover, we demonstrate that SA and MeSA inhibited citrus canker caused by <jats:italic>Xanthomonas citri<\/jats:italic>, whereas an inhibitor of CsMES1 enhanced canker formation, suggesting that CsMES1 and SA play a role in the local defense against citrus canker bacteria.<\/jats:p>","DOI":"10.1038\/s41598-019-40552-3","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T11:03:04Z","timestamp":1551956584000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Structure-function relationship of a citrus salicylate methylesterase and role of salicylic acid in citrus canker resistance"],"prefix":"10.1038","volume":"9","author":[{"given":"Caio Cesar de","family":"Lima Silva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo Massayoshi","family":"Shimo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"de Fel\u00edcio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Fernando","family":"Mercaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana Aparecida","family":"Rocco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-0256","authenticated-orcid":false,"given":"Celso Eduardo","family":"Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"40552_CR1","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1134\/S0003683807040011","volume":"43","author":"NI Vasyukova","year":"2007","unstructured":"Vasyukova, N. I. & Ozeretskovskaya, O. L. Induced plant resistance and salicylic acid: A review. Applied Biochem. Microbiol. 43, 367\u2013373 (2007).","journal-title":"Applied Biochem. Microbiol."},{"key":"40552_CR2","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1146\/annurev.phyto.050908.135202","volume":"47","author":"AC Vlot","year":"2009","unstructured":"Vlot, A. C., Dempsey, D. A. & Klessig, D. F. Salicylic Acid, a multifaceted hormone to combat disease. Annu Rev Phytopathol. 47, 177\u2013206 (2009).","journal-title":"Annu Rev Phytopathol."},{"key":"40552_CR3","doi-asserted-by":"publisher","first-page":"e0156","DOI":"10.1199\/tab.0156","volume":"9","author":"DA Dempsey","year":"2011","unstructured":"Dempsey, D. A., Vlot, A. C., Wildermuth, M. C. & Klessig, D. F. Salicylic Acid biosynthesis and metabolism. Arabidopsis Book. 9, e0156 (2011).","journal-title":"Arabidopsis Book."},{"key":"40552_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-017-0364-8","volume":"15","author":"DA Dempsey","year":"2017","unstructured":"Dempsey, D. A. & Klessig, D. F. How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans? BMC Biol. 15, 23 (2017).","journal-title":"BMC Biol."},{"key":"40552_CR5","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.celrep.2012.05.008","volume":"1","author":"Y Wu","year":"2012","unstructured":"Wu, Y. et al. The Arabidopsis NPR1 protein is a receptor for the plant defense hormone salicylic acid. Cell Rep. 1, 639\u2013647 (2012).","journal-title":"Cell Rep."},{"key":"40552_CR6","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/35107108","volume":"414","author":"MC Wildermuth","year":"2001","unstructured":"Wildermuth, M. C., Dewdney, J., Wu, G. & Ausubel, F. M. Isochorismate synthase is required to synthesize salicylic acid for plant defence. Nature 414, 562\u2013565 (2001).","journal-title":"Nature"},{"key":"40552_CR7","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.pbi.2007.08.008","volume":"10","author":"G Loake","year":"2007","unstructured":"Loake, G. & Grant, M. Salicylic acid in plant defence - the players and protagonists. Curr Opin Plant Biol. 10, 466\u2013472 (2007).","journal-title":"Curr Opin Plant Biol."},{"key":"40552_CR8","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1111\/nph.14078","volume":"212","author":"MB Shine","year":"2016","unstructured":"Shine, M. B. et al. Cooperative functioning between phenylalanine ammonia lyase and isochorismate synthase activities contributes to salicylic acid biosynthesis in soybean. New Phytol. 212, 627\u2013636 (2016).","journal-title":"New Phytol."},{"key":"40552_CR9","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1126\/science.1147113","volume":"318","author":"SW Park","year":"2007","unstructured":"Park, S. W., Kaimoyo, E., Kumar, D., Mosher, S. & Klessig, D. F. Methyl salicylate is a critical mobile signal for plant systemic acquired resistance. Science 318, 113\u2013116 (2007).","journal-title":"Science"},{"key":"40552_CR10","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3389\/fpls.2013.00030","volume":"4","author":"J Shah","year":"2013","unstructured":"Shah, J. & Zeier, J. Long-distance communication and signal amplification in systemic acquired resistance. Front Plant Sci. 4, 30 (2013).","journal-title":"Front Plant Sci."},{"key":"40552_CR11","first-page":"95","volume":"37","author":"JC D\u2019Auria","year":"2003","unstructured":"D\u2019Auria, J. C., Chen, F. & Pichersky, E. The SABATH family of methyltransferases in Arabidopsis thaliana and other plant species. Rec. Adv. Phytochem. 37, 95\u2013125 (2003).","journal-title":"Rec. Adv. Phytochem."},{"key":"40552_CR12","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1105\/tpc.014548","volume":"15","author":"C Zubieta","year":"2003","unstructured":"Zubieta, C. et al. Structural basis for substrate recognition in the salicylic acid carboxyl methyltransferase family. Plant Cell. 15, 1704\u20131716 (2003).","journal-title":"Plant Cell."},{"key":"40552_CR13","doi-asserted-by":"publisher","first-page":"7307","DOI":"10.1074\/jbc.M807968200","volume":"284","author":"SW Park","year":"2009","unstructured":"Park, S. W. et al. Use of a synthetic salicylic acid analog to investigate the roles of methyl salicylate and its esterases in plant disease resistance. J Biol Chem. 284, 7307\u20137317 (2009).","journal-title":"J Biol Chem."},{"key":"40552_CR14","doi-asserted-by":"publisher","first-page":"1773","DOI":"10.1073\/pnas.0409227102","volume":"102","author":"F Forouhar","year":"2005","unstructured":"Forouhar, F. et al. Structural and biochemical studies identify tobacco SABP2 as a methyl salicylate esterase and implicate it in plant innate immunity. Proc Natl Acad Sci USA 102, 1773\u20131778 (2005).","journal-title":"Proc Natl Acad Sci USA"},{"key":"40552_CR15","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1111\/j.1365-313X.2008.03618.x","volume":"56","author":"AC Vlot","year":"2008","unstructured":"Vlot, A. C. et al. Identification of likely orthologs of tobacco salicylic acid-binding protein 2 and their role in systemic acquired resistance in Arabidopsis thaliana. Plant J. 56, 445\u2013456 (2008).","journal-title":"Plant J."},{"key":"40552_CR16","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1016\/j.phytochem.2008.11.014","volume":"70","author":"N Zhao","year":"2009","unstructured":"Zhao, N. et al. Two poplar methyl salicylate esterases display comparable biochemical properties but divergent expression patterns. Phytochemistry 70, 32\u201339 (2009).","journal-title":"Phytochemistry"},{"key":"40552_CR17","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1094\/MPMI-23-9-1151","volume":"23","author":"PM Manosalva","year":"2010","unstructured":"Manosalva, P. M. et al. Methyl esterase 1 (StMES1) is required for systemic acquired resistance in potato. Mol Plant Microbe Interact. 23, 1151\u20131163 (2010).","journal-title":"Mol Plant Microbe Interact."},{"key":"40552_CR18","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1104\/pp.113.4.1319","volume":"113","author":"H Du","year":"1997","unstructured":"Du, H. & Klessig, D. F. Identification of a soluble, high-affinity salicylic acid-binding protein in tobacco. Plant Physiol. 113, 1319\u20131327 (1997).","journal-title":"Plant Physiol."},{"key":"40552_CR19","doi-asserted-by":"publisher","first-page":"16101","DOI":"10.1073\/pnas.0307162100","volume":"100","author":"D Kumar","year":"2003","unstructured":"Kumar, D. & Klessig, D. F. High-affinity salicylic acid-binding protein 2 is required for plant innate immunity and has salicylic acid-stimulated lipase activity. Proc Natl Acad Sci USA 100, 16101\u201316106 (2003).","journal-title":"Proc Natl Acad Sci USA"},{"key":"40552_CR20","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1111\/j.1365-313X.2005.02645.x","volume":"45","author":"D Kumar","year":"2006","unstructured":"Kumar, D., Gustafsson, C. & Klessig, D. F. Validation of RNAi silencing specificity using synthetic genes: salicylic acid-binding protein 2 is required for innate immunity in plants. Plant J. 45, 863\u2013868 (2006).","journal-title":"Plant J."},{"key":"40552_CR21","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1111\/j.1364-3703.2008.00486.x","volume":"9","author":"RA Cernadas","year":"2008","unstructured":"Cernadas, R. A., Camillo, L. R. & Benedetti, C. E. Transcriptional analysis of the sweet orange interaction with the citrus canker pathogens Xanthomonas axonopodis pv. citri and Xanthomonas axonopodis pv. aurantifolii. Mol Plant Pathol. 9, 609\u2013631 (2008).","journal-title":"Mol Plant Pathol."},{"key":"40552_CR22","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1111\/mpp.12359","volume":"17","author":"VY Abe","year":"2016","unstructured":"Abe, V. Y. & Benedetti, C. E. Additive roles of PthAs in bacterial growth and pathogenicity associated with nucleotide polymorphisms in effector-binding elements of citrus canker susceptibility genes. Mol Plant Pathol. 17, 1223\u20131236 (2016).","journal-title":"Mol Plant Pathol."},{"key":"40552_CR23","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1034\/j.1399-3054.2001.1130215.x","volume":"113","author":"GY Zhong","year":"2001","unstructured":"Zhong, G. Y., Goren, R., Riov, J., Sisler, E. C. & Holland, D. Characterization of an ethylene-induced esterase gene isolated from Citrus sinensis by competitive hybridization. Physiol. Plantarum 113, 267\u2013274 (2001).","journal-title":"Physiol. Plantarum"},{"key":"40552_CR24","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1104\/pp.108.118224","volume":"147","author":"Y Yang","year":"2008","unstructured":"Yang, Y. et al. Inactive methyl indole-3-acetic acid ester can be hydrolyzed and activated by several esterases belonging to the AtMES esterase family of Arabidopsis. Plant Physiol. 147, 1034\u20131045 (2008).","journal-title":"Plant Physiol."},{"key":"40552_CR25","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1023\/A:1011625619713","volume":"46","author":"C Betz","year":"2001","unstructured":"Betz, C., McCollum, T. G. & Mayer, R. T. Differential expression of two cinnamate 4-hydroxylase genes in \u2018Valencia\u2019 orange (Citrus sinensis Osbeck). Plant Mol Biol. 46, 741\u2013748 (2001).","journal-title":"Plant Mol Biol."},{"key":"40552_CR26","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1021\/jp1086812","volume":"115","author":"J Yao","year":"2011","unstructured":"Yao, J., Xu, Q., Chen, F. & Guo, H. QM\/MM free energy simulations of salicylic acid methyltransferase: effects of stabilization of TS-like structures on substrate specificity. J Phys Chem B. 115, 389\u2013396 (2011).","journal-title":"J Phys Chem B."},{"key":"40552_CR27","doi-asserted-by":"publisher","first-page":"14807","DOI":"10.1073\/pnas.1302702110","volume":"110","author":"K Zhang","year":"2013","unstructured":"Zhang, K., Halitschke, R., Yin, C., Liu, C. J. & Gan, S. S. Salicylic acid 3-hydroxylase regulates Arabidopsis leaf longevity by mediating salicylic acid catabolism. Proc. Natl. Acad. Sci. USA 110, 14807\u201314812 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"40552_CR28","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1104\/pp.17.00695","volume":"175","author":"Y Zhang","year":"2017","unstructured":"Zhang, Y. et al. S5H\/DMR6 Encodes a Salicylic Acid 5-Hydroxylase that fine-tunes Salicylic Acid homeostasis. Plant Physiol. 175, 1082\u20131093 (2017).","journal-title":"Plant Physiol."},{"key":"40552_CR29","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1111\/mpp.12489","volume":"18","author":"RA Roeschlin","year":"2017","unstructured":"Roeschlin, R. A. et al. Resistance to citrus canker induced by a variant of Xanthomonas citri ssp. citri is associated with a hypersensitive cell death response involving autophagy-associated vacuolar processes. Mol Plant Pathol. 18, 1267\u20131281 (2017).","journal-title":"Mol Plant Pathol."},{"key":"40552_CR30","doi-asserted-by":"publisher","first-page":"1143","DOI":"10.1016\/j.jplph.2012.03.018","volume":"169","author":"Y Wang","year":"2012","unstructured":"Wang, Y. & Liu, J. H. Exogenous treatment with salicylic acid attenuates occurrence of citrus canker in susceptible navel orange (Citrus sinensis Osbeck). J Plant Physiol. 169, 1143\u20131149 (2012).","journal-title":"J Plant Physiol."},{"key":"40552_CR31","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1007\/s10658-010-9633-x","volume":"128","author":"X Zhang","year":"2010","unstructured":"Zhang, X. et al. Over-expression of the Arabidopsis NPR1 gene in citrus increases resistance to citrus canker. Eur. J. Plant Pathol. 128, 91\u2013100 (2010).","journal-title":"Eur. J. Plant Pathol."},{"key":"40552_CR32","first-page":"1","volume":"1","author":"RL Boscariol-Camargo","year":"2016","unstructured":"Boscariol-Camargo, R. L., Takita, M. A. & Machado, M. A. Bacterial resistance in AtNPR1 transgenic sweet orange is mediated by priming and involves EDS1 and PR2. Tropical. Plant Pathology 1, 1\u20139 (2016).","journal-title":"Plant Pathology"},{"key":"40552_CR33","doi-asserted-by":"publisher","first-page":"e31130","DOI":"10.1371\/journal.pone.0031130","volume":"7","author":"C An","year":"2012","unstructured":"An, C. & Mou, Z. Non-host defense response in a novel Arabidopsis-Xanthomonas citri subsp. citri pathosystem. PLoS One. 7, e31130 (2012).","journal-title":"PLoS One."},{"key":"40552_CR34","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1094\/PDIS.2004.88.7.745","volume":"88","author":"JH Graham","year":"2004","unstructured":"Graham, J. H. & Leite, R. P. Jr. Lack of control of Citrus Canker by induced systemic resistance compounds. Plant Disease 88, 745\u2013750 (2004).","journal-title":"Plant Disease"},{"key":"40552_CR35","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/s10658-008-9415-x","volume":"124","author":"MI Francis","year":"2009","unstructured":"Francis, M. I., Redondo, A., Burns, J. K. & Graham, J. H. Soil application of imidacloprid and related SAR-inducing compounds produces effective and persistent control of citrus canker. Eur. J. Plant Pathol. 124, 283\u2013292 (2009).","journal-title":"Eur. J. Plant Pathol."},{"key":"40552_CR36","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1094\/PDIS-09-10-0653","volume":"95","author":"JH Graham","year":"2011","unstructured":"Graham, J. H. & Myers, M. E. Soil application of SAR inducers imidacloprid, thiamethoxam, and acibenzolar-S-methyl for Citrus Canker control in young grapefruit trees. Plant Disease 95, 725\u2013728 (2011).","journal-title":"Plant Disease"},{"key":"40552_CR37","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.cropro.2013.09.002","volume":"54","author":"JH Graham","year":"2013","unstructured":"Graham, J. H. & Myers, M. E. Integration of soil applied neonicotinoid insecticides and acibenzolar-S-methyl for systemic acquired resistance (SAR) control of citrus canker on young citrus trees. Crop Protection 54, 239\u2013243 (2013).","journal-title":"Crop Protection"},{"key":"40552_CR38","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1094\/MPMI-04-13-0122-R","volume":"26","author":"MLP de Oliveira","year":"2013","unstructured":"de Oliveira, M. L. P. et al. Increased resistance against citrus canker mediated by a citrus mitogen-activated protein kinase. Mol. Plant-Microbe Interact. 26, 1190\u20131199 (2013).","journal-title":"Mol. Plant-Microbe Interact."},{"key":"40552_CR39","first-page":"4959","volume":"7","author":"SU Park","year":"2008","unstructured":"Park, S. U., Uddin, R., Xu, H., Kim, Y. K. & Lee, S. Y. Biotechnological applications for rosmarinic acid production in plant. African J. Biotechnol. 7, 4959\u20134965 (2008).","journal-title":"African J. Biotechnol."},{"key":"40552_CR40","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1016\/j.phytochem.2009.05.010","volume":"70","author":"M Petersen","year":"2009","unstructured":"Petersen, M. et al. Evolution of rosmarinic acid biosynthesis. Phytochemistry 70, 1663\u20131679 (2009).","journal-title":"Phytochemistry"},{"issue":"409","key":"40552_CR41","doi-asserted-by":"publisher","first-page":"ra1","DOI":"10.1126\/scisignal.aaa8271","volume":"9","author":"A Corral-Lugo","year":"2016","unstructured":"Corral-Lugo, A., Daddaoua, A., Ortega, A., Espinosa-Urgel, M. & Krell, T. Rosmarinic acid is a homoserine lactone mimic produced by plants that activates a bacterial quorum-sensing regulator. Sci Signal. 9(409), ra1 (2016).","journal-title":"Sci Signal."},{"issue":"W1","key":"40552_CR42","doi-asserted-by":"publisher","first-page":"W296","DOI":"10.1093\/nar\/gky427","volume":"46","author":"A Waterhouse","year":"2018","unstructured":"Waterhouse, A. et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 46(W1), W296\u2013W303 (2018).","journal-title":"Nucleic Acids Res."},{"key":"40552_CR43","doi-asserted-by":"publisher","first-page":"2785","DOI":"10.1002\/jcc.21256","volume":"16","author":"GM Morris","year":"2009","unstructured":"Morris, G. M. et al. Autodock4 and AutoDockTools4: automated docking with selective receptor flexibility. J. Computational Chemistry. 16, 2785\u201391 (2009).","journal-title":"J. Computational Chemistry."},{"key":"40552_CR44","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","volume":"3","author":"NM O\u2019Boyle","year":"2011","unstructured":"O\u2019Boyle, N. M. et al. Open Bable: An open chemical toolbox. J. Cheminform. 3, 33 (2011).","journal-title":"J. Cheminform."},{"key":"40552_CR45","doi-asserted-by":"publisher","first-page":"1360","DOI":"10.1016\/j.str.2017.07.004","volume":"25","author":"AS Soprano","year":"2017","unstructured":"Soprano, A. S. et al. Crystal structure and regulation of the citrus Pol III repressor MAF1 by auxin and phosphorylation. Structure 25, 1360\u20131370 (2017).","journal-title":"Structure"},{"key":"40552_CR46","doi-asserted-by":"publisher","first-page":"e31263","DOI":"10.1371\/journal.pone.0031263","volume":"7","author":"V Mafra","year":"2012","unstructured":"Mafra, V. et al. Reference genes for accurate transcript normalization in citrus genotypes under different experimental conditions. PLoS ONE 7, e31263 (2012).","journal-title":"PLoS ONE"},{"key":"40552_CR47","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.1021\/np400413s","volume":"76","author":"JY Yang","year":"2013","unstructured":"Yang, J. Y. et al. Molecular networking as a dereplication strategy. J Nat Prod. 76, 1686\u201399 (2013).","journal-title":"J Nat Prod."},{"key":"40552_CR48","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nbt.3597","volume":"34","author":"M Wang","year":"2016","unstructured":"Wang, M. et al. Sharing and community curation of mass spectrometry data with Global Natural Products Social molecular metworking. Nat Biotechnol. 34, 828\u2013837 (2016).","journal-title":"Nat Biotechnol."},{"key":"40552_CR49","doi-asserted-by":"publisher","first-page":"3317","DOI":"10.1021\/acs.analchem.5b04804","volume":"88","author":"PM Allard","year":"2016","unstructured":"Allard, P. M. et al. Integration of molecular networking and in-silico MS\/MS fragmentation for natural products dereplication. Anal Chem. 88, 3317\u20133323 (2016).","journal-title":"Anal Chem."},{"key":"40552_CR50","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1021\/acs.jnatprod.7b00737","volume":"81","author":"LF Nothias","year":"2018","unstructured":"Nothias, L. F. et al. Bioactivity-based molecular networking for the discovery of drug leads in natural product bioassay-guided fractionation. J Nat Prod. 81, 758\u2013767 (2018).","journal-title":"J Nat Prod."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40552-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40552-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40552-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T07:12:14Z","timestamp":1671261134000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-40552-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,7]]},"references-count":50,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["40552"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-40552-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,7]]},"assertion":[{"value":"14 November 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"3901"}}