{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:29:19Z","timestamp":1792610959271,"version":"4.5.0"},"reference-count":155,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100008460","name":"National Center for Complementary and Integrative Health","doi-asserted-by":"publisher","award":["NIH-2R15AT008277-02"],"award-info":[{"award-number":["NIH-2R15AT008277-02"]}],"id":[{"id":"10.13039\/100008460","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Planta"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1007\/s00425-021-03676-3","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T23:39:16Z","timestamp":1626305956000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":71,"title":["Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches"],"prefix":"10.1007","volume":"254","author":[{"given":"Kaiser Iqbal","family":"Wani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadaf","family":"Choudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andleeb","family":"Zehra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Naeem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Weathers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5927-719X","authenticated-orcid":false,"given":"Tariq","family":"Aftab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"3676_CR1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s11738-015-1771-5","volume":"37","author":"MZ Abdin","year":"2015","unstructured":"Abdin MZ, Alam P (2015) Genetic engineering of artemisinin biosynthesis: prospects to improve its production. Acta Physiol Plant 37:33. https:\/\/doi.org\/10.1007\/s11738-015-1771-5","journal-title":"Acta Physiol Plant"},{"key":"3676_CR2","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1055\/s-2003-38871","volume":"69","author":"MZ Abdin","year":"2003","unstructured":"Abdin MZ, Israr M, Rehman RU, Jain SK (2003) Artemisinin, a novel antimalarial drug: biochemical and molecular approaches for enhanced production. Planta Med 69:289\u2013299. https:\/\/doi.org\/10.1055\/s-2003-38871","journal-title":"Planta Med"},{"key":"3676_CR3","first-page":"25","volume":"5","author":"T Aftab","year":"2010","unstructured":"Aftab T, Khan MMA, Idrees M, Naeem M, Hashmi N (2010a) Effects of gibberellic acid on growth, photosynthetic efficiency and artemisinin content of Artemisia annua L. Med Aromat Plant Sci Biotechnol 5:25\u201329","journal-title":"Med Aromat Plant Sci Biotechnol"},{"key":"3676_CR4","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1080\/17429141003647137","volume":"5","author":"T Aftab","year":"2010","unstructured":"Aftab T, Khan MMA, Idrees M, Naeem M, Singh M, Ram M (2010b) Stimulation of crop productivity, photosynthesis and artemisinin production in Artemisia annua L. by triacontanol and gibberellic acid application. J Plant Interact 5:273\u2013281. https:\/\/doi.org\/10.1080\/17429141003647137","journal-title":"J Plant Interact"},{"key":"3676_CR5","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1111\/j.1439-037X.2010.00427.x","volume":"196","author":"T Aftab","year":"2010","unstructured":"Aftab T, Khan MMA, Idrees M, Naeem M, Ram M (2010c) Boron induced oxidative stress, antioxidant defence response and changes in artemisinin content in Artemisia annua L. J Agron Crop Sci 196:423\u2013430. https:\/\/doi.org\/10.1111\/j.1439-037X.2010.00427.x","journal-title":"J Agron Crop Sci"},{"key":"3676_CR6","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s00344-011-9205-0","volume":"30","author":"T Aftab","year":"2011","unstructured":"Aftab T, Khan MMA, da Silva JAT, Idrees M, Naeem M (2011a) Role of salicylic acid in promoting salt stress tolerance and enhanced artemisinin production in Artemisia annua L. J Plant Growth Regul 30:425\u2013435. https:\/\/doi.org\/10.1007\/s00344-011-9205-0","journal-title":"J Plant Growth Regul"},{"key":"3676_CR7","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1007\/s00709-010-0218-5","volume":"248","author":"T Aftab","year":"2011","unstructured":"Aftab T, Khan MMA, Idrees M, Naeem M, Hashmi N (2011b) Methyl jasmonate counteracts boron toxicity by preventing oxidative stress and regulating antioxidant enzyme activities and artemisinin biosynthesis in Artemisia annua L. Protoplasma 248:601\u2013612. https:\/\/doi.org\/10.1007\/s00709-010-0218-5","journal-title":"Protoplasma"},{"key":"3676_CR8","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1007\/s00299-011-1099-6","volume":"30","author":"P Alam","year":"2011","unstructured":"Alam P, Abdin M (2011) Over-expression of HMG-CoA reductase and amorpha-4, 11-diene synthase genes in Artemisia annua L. and its influence on artemisinin content. Plant Cell Rep 30:1919\u20131928. https:\/\/doi.org\/10.1007\/s00299-011-1099-6","journal-title":"Plant Cell Rep"},{"key":"3676_CR9","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1007\/s00425-011-1430-z","volume":"234","author":"F Alejos-Gonzalez","year":"2011","unstructured":"Alejos-Gonzalez F, Qu GS, Zhou LL, Saravitz CH, Shurtleff JL, Xie DY (2011) Characterization of development and artemisinin biosynthesis in self-pollinated Artemisia annua plants. Planta 234:685\u2013697. https:\/\/doi.org\/10.1007\/s00425-011-1430-z","journal-title":"Planta"},{"key":"3676_CR10","doi-asserted-by":"publisher","first-page":"2206","DOI":"10.4236\/ajps.2013.411274","volume":"4","author":"F Alejos-Gonzalez","year":"2013","unstructured":"Alejos-Gonzalez F, Perkins K, Winston MI, Xie DY (2013) Efficient somatic embryogenesis and organogenesis of self-pollination Artemisia annua progeny and artemisinin formation in regenerated plants. Am J Plant Sci 4:2206. https:\/\/doi.org\/10.4236\/ajps.2013.411274","journal-title":"Am J Plant Sci"},{"key":"3676_CR11","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s11274-015-1972-5","volume":"32","author":"M Arora","year":"2016","unstructured":"Arora M, Saxena P, Choudhary DK, Abdin MZ, Varma A (2016) Dual symbiosis between Piriformospora indica and Azotobacter chroococcum enhances the artemisinin content in Artemisia annua L. World J Microbiol Biotechnol 32:19. https:\/\/doi.org\/10.1007\/s11274-015-1972-5","journal-title":"World J Microbiol Biotechnol"},{"key":"3676_CR12","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1007\/s13199-017-0519-y","volume":"75","author":"M Arora","year":"2018","unstructured":"Arora M, Saxena P, Abdin MZ, Varma A (2018) Interaction between Piriformospora indica and Azotobacter chroococcum governs better plant physiological and biochemical parameters in Artemisia annua L. plants grown under in vitro conditions. Symbiosis 75:103\u2013112. https:\/\/doi.org\/10.1007\/s13199-017-0519-y","journal-title":"Symbiosis"},{"key":"3676_CR13","doi-asserted-by":"publisher","first-page":"2302","DOI":"10.3390\/molecules15042302","volume":"15","author":"PR Arsenault","year":"2010","unstructured":"Arsenault PR, Vail DR, Wobbe KK, Weathers PJ (2010) Effect of sugars on artemisinin production in Artemisia annua L. transcription and metabolite measurements. Molecules 15:2302\u20132318. https:\/\/doi.org\/10.3390\/molecules15042302","journal-title":"Molecules"},{"key":"3676_CR14","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.apsoil.2011.06.005","volume":"49","author":"A Awasthi","year":"2011","unstructured":"Awasthi A, Bharti N, Nair P, Singh R, Shukla AK, Gupta MM, Kalra A (2011) Synergistic effect of Glomus mosseae and nitrogen fixing Bacillus subtilis strain Daz26 on artemisinin content in Artemisia annua L. Appl Soil Ecol 49:125\u2013130. https:\/\/doi.org\/10.1016\/j.apsoil.2011.06.005","journal-title":"Appl Soil Ecol"},{"key":"3676_CR15","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1007\/s11240-010-9775-8","volume":"103","author":"W Banyai","year":"2010","unstructured":"Banyai W, Kirdmanee C, Mii M, Supaibulwatana K (2010a) Overexpression of farnesyl pyrophosphate synthase (FPS) gene affected artemisinin content and growth of Artemisia annua L. Plant Cell Tissue Organ Cult 103:255\u2013265. https:\/\/doi.org\/10.1007\/s11240-010-9775-8","journal-title":"Plant Cell Tissue Organ Cult"},{"key":"3676_CR16","doi-asserted-by":"publisher","first-page":"427","DOI":"10.5511\/plantbiotechnology.10.0726a","volume":"27","author":"W Banyai","year":"2010","unstructured":"Banyai W, Sangthong R, Karaket N, Inthima P, Mii M, Supaibulwatana K (2010b) Overproduction of artemisinin in tetraploid Artemisia annua L. Plant Biotechnol 27:427\u2013433. https:\/\/doi.org\/10.5511\/plantbiotechnology.10.0726a","journal-title":"Plant Biotechnol"},{"key":"3676_CR17","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1007\/s10725-010-9510-9","volume":"63","author":"W Banyai","year":"2011","unstructured":"Banyai W, Mii M, Supaibulwatana K (2011) Enhancement of artemisinin content and biomass in Artemisia annua by exogenous GA3 treatment. Plant Growth Regul 63:45\u201354. https:\/\/doi.org\/10.1007\/s10725-010-9510-9","journal-title":"Plant Growth Regul"},{"key":"3676_CR18","doi-asserted-by":"publisher","first-page":"3594","DOI":"10.1128\/JCM.37.11.3594-3600.1999","volume":"37","author":"G Berg","year":"1999","unstructured":"Berg G, Roskot N, Smalla K (1999) Genotypic and phenotypic relationships between clinical and environmental isolates of Stenotrophomonas maltophilia. J Clin Microbiol 37:3594\u20133600. https:\/\/doi.org\/10.1128\/JCM.37.11.3594-3600.1999","journal-title":"J Clin Microbiol"},{"key":"3676_CR19","unstructured":"Bhakuni RS, Jain DC, Sharma RP, Kumar S (2001) Secondary metabolites of Artemisia annua and their biological activity. Curr Sci 35\u201348"},{"key":"3676_CR20","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/S0031-9422(99)00206-X","volume":"52","author":"HJ Bouwmeester","year":"1999","unstructured":"Bouwmeester HJ, Wallaart TE, Janssen MH, van Loo B, Jansen BJ, Posthumus MA, Franssen MC (1999) Amorpha-4, 11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry 52:843\u2013854. https:\/\/doi.org\/10.1016\/S0031-9422(99)00206-X","journal-title":"Phytochemistry"},{"key":"3676_CR21","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.indcrop.2012.02.018","volume":"39","author":"EA Brisibe","year":"2012","unstructured":"Brisibe EA, Udensi O, Chukwurah PN, de Magalh\u00e4es PM, Figueira GM, Ferreira JF (2012) Adaptation and agronomic performance of Artemisia annua L. under lowland humid tropical conditions. Ind Crops Prod 39:190\u2013197. https:\/\/doi.org\/10.1016\/j.indcrop.2012.02.018","journal-title":"Ind Crops Prod"},{"key":"3676_CR22","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1016\/S0031-9422(02)00265-0","volume":"61","author":"Y Cai","year":"2002","unstructured":"Cai Y, Jia JW, Crock J, Lin ZX, Chen XY, Croteau R (2002) A cDNA clone for \u03b2-caryophyllene synthase from Artemisia annua. Phytochemistry 61:523\u2013529. https:\/\/doi.org\/10.1016\/S0031-9422(02)00265-0","journal-title":"Phytochemistry"},{"key":"3676_CR23","doi-asserted-by":"publisher","first-page":"893","DOI":"10.3389\/fmicb.2015.00893","volume":"6","author":"YT Chang","year":"2015","unstructured":"Chang YT, Lin CY, Chen YH, Hsueh PR (2015) Update on infections caused by Stenotrophomonas maltophilia with particular attention to resistance mechanisms and therapeutic options. Front Microbiol 6:893. https:\/\/doi.org\/10.3389\/fmicb.2015.00893","journal-title":"Front Microbiol"},{"key":"3676_CR24","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.apsoil.2008.04.003","volume":"40","author":"V Chaudhary","year":"2008","unstructured":"Chaudhary V, Kapoor R, Bhatnagar AK (2008) Effectiveness of two arbuscular mycorrhizal fungi on concentrations of essential oil and artemisinin in three accessions of Artemisia annua L. Appl Soil Ecol 40:174\u2013181. https:\/\/doi.org\/10.1016\/j.apsoil.2008.04.003","journal-title":"Appl Soil Ecol"},{"key":"3676_CR25","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/S0168-9452(00)00217-X","volume":"155","author":"DH Chen","year":"2000","unstructured":"Chen DH, Ye HC, Li GF (2000) Expression of a chimeric farnesyl diphosphate synthase gene in Artemisia annua L. transgenic plants via Agrobacterium tumefaciens-mediated transformation. Plant Sci 155:179\u2013185. https:\/\/doi.org\/10.1016\/S0168-9452(00)00217-X","journal-title":"Plant Sci"},{"key":"3676_CR26","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1055\/s-0030-1271038","volume":"77","author":"JL Chen","year":"2011","unstructured":"Chen JL, Fang HM, Ji YP, Pu GB, Guo YW, Huang LL, Du ZG, Liu BY, Ye HC, Li GF, Wang H (2011) Artemisinin biosynthesis enhancement in transgenic Artemisia annua plants by downregulation of the \u03b2-caryophyllene synthase gene. Planta Med 77:1759\u20131765. https:\/\/doi.org\/10.1055\/s-0030-1271038","journal-title":"Planta Med"},{"key":"3676_CR27","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1007\/s11816-012-0262-z","volume":"7","author":"Y Chen","year":"2012","unstructured":"Chen Y, Shen Q, Wang Y, Wang T, Wu S, Zhang L, Gao E (2012) The stacked over-expression of FPS, CYP71AV1 and CPR genes leads to the increase of artemisinin level in Artemisia annua L. Plant Biotechnol Rep 7:287\u2013295. https:\/\/doi.org\/10.1007\/s11816-012-0262-z","journal-title":"Plant Biotechnol Rep"},{"key":"3676_CR28","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.2174\/0929867013371563","volume":"8","author":"P Christen","year":"2001","unstructured":"Christen P, Veuthey JL (2001) New trends in extraction, identification and quantification of artemisinin and its derivatives. Curr Med Chem 8:1827\u20131839. https:\/\/doi.org\/10.2174\/0929867013371563","journal-title":"Curr Med Chem"},{"key":"3676_CR29","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1017\/S1479262112000159","volume":"10","author":"J Cockram","year":"2012","unstructured":"Cockram J, Hill C, Burns C, Arroo RR, Woolley JG, Flockart I, Greenland AJ (2012) Screening a diverse collection of Artemisia annua germplasm accessions for the antimalarial compound, artemisinin. Plant Genet Resour 10:152\u2013154. https:\/\/doi.org\/10.1017\/S1479262112000159","journal-title":"Plant Genet Resour"},{"key":"3676_CR30","doi-asserted-by":"publisher","first-page":"594565","DOI":"10.3389\/fpls.2020.594565","volume":"11","author":"T Czechowski","year":"2020","unstructured":"Czechowski T, Weathers PJ, Brodelius PE, Brown GD, Graham IA (2020) Editorial: artemisinin\u2014from traditional chinese medicine to artemisinin combination therapies; four decades of research on the biochemistry, physiology, and breeding of Artemisia annua. Front Plant Sci 11:594565. https:\/\/doi.org\/10.3389\/fpls.2020.594565","journal-title":"Front Plant Sci"},{"key":"3676_CR31","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.phymed.2017.04.006","volume":"32","author":"NB Daddy","year":"2017","unstructured":"Daddy NB, Kalisya LM, Bagire PG, Watt RL, Towler MJ, Weathers PJ (2017) Artemisia annua dried leaf tablets treated malaria resistant to ACT and iv artesunate. Phytomedicine 32:37\u201340. https:\/\/doi.org\/10.1016\/j.phymed.2017.04.006","journal-title":"Phytomedicine"},{"key":"3676_CR32","first-page":"2","volume":"8","author":"BS Darki","year":"2019","unstructured":"Darki BS, Shabani L, Pourvaez R, Mostafa S (2019) Effects of CuSO4 and AgNO3 on artemisinin and phenolic compound in shoot cultures of Artemisia annua L. J Plant Proc Func 8:2","journal-title":"J Plant Proc Func"},{"key":"3676_CR33","doi-asserted-by":"publisher","first-page":"1795","DOI":"10.2174\/0929867013371635","volume":"8","author":"N Delabays","year":"2001","unstructured":"Delabays N, Simonnet X, Gaudin M (2001) The genetics of artemisinin content in Artemisia annua L. and the breeding of high yielding cultivars. Curr Med Chem 8:1795\u20131801. https:\/\/doi.org\/10.2174\/0929867013371635","journal-title":"Curr Med Chem"},{"key":"3676_CR34","doi-asserted-by":"publisher","first-page":"254","DOI":"10.3390\/biom10020254","volume":"10","author":"MR Desrosiers","year":"2020","unstructured":"Desrosiers MR, Mittelman A, Weathers PJ (2020) Dried leaf Artemisia Annua improves bioavailability of artemisinin via cytochrome P450 inhibition and enhances artemisinin efficacy downstream. Biomolecules 10:254. https:\/\/doi.org\/10.3390\/biom10020254","journal-title":"Biomolecules"},{"key":"3676_CR35","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1016\/j.apsb.2020.09.001","volume":"11","author":"D Dolivo","year":"2021","unstructured":"Dolivo D, Weathers P, Dominko T (2021) Artemisinin and artemisinin derivatives as antifibrotic therapeutics. Acta Pharm Sin B.\u00a011:322-339. https:\/\/doi.org\/10.1016\/j.apsb.2020.09.001","journal-title":"Acta Pharm Sin B"},{"key":"3676_CR36","doi-asserted-by":"publisher","first-page":"478","DOI":"10.3389\/fpls.2018.00478","volume":"9","author":"E Domokos","year":"2018","unstructured":"Domokos E, Jakab-Farkas L, Dark\u00f3 B, B\u00edr\u00f3-Janka B, Mara G, Albert C, Balog A (2018) Increase in Artemisia annua plant biomass artemisinin content and guaiacol peroxidase activity using the arbuscular mycorrhizal fungus Rhizophagus irregularis. Front Plant Sci 9:478. https:\/\/doi.org\/10.3389\/fpls.2018.00478","journal-title":"Front Plant Sci"},{"key":"3676_CR37","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1086\/297173","volume":"155","author":"MV Duke","year":"1994","unstructured":"Duke MV, Paul RN, Elsohly HN, Sturtz G, Duke SO (1994) Localization of artemisinin and artemisitene in foliar tissues of glanded and glandless biotypes of Artemisia annua L. Int J Plant Sci 155:365\u2013372. https:\/\/doi.org\/10.1086\/297173","journal-title":"Int J Plant Sci"},{"key":"3676_CR38","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1038\/nrmicro2239","volume":"7","author":"RT Eastman","year":"2009","unstructured":"Eastman RT, Fidock DA (2009) Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nat Rev Microbiol 7:864\u2013874. https:\/\/doi.org\/10.1038\/nrmicro2239","journal-title":"Nat Rev Microbiol"},{"key":"3676_CR39","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.semcancer.2017.02.009","volume-title":"Seminars in cancer biology","author":"T Efferth","year":"2017","unstructured":"Efferth T (2017) From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy. Seminars in cancer biology, vol 46. Academic Press, Cambridge, pp 65\u201383. https:\/\/doi.org\/10.1016\/j.semcancer.2017.02.009"},{"key":"3676_CR40","doi-asserted-by":"publisher","first-page":"1730","DOI":"10.1016\/j.biotechadv.2018.01.001","volume":"36","author":"T Efferth","year":"2018","unstructured":"Efferth T (2018) Beyond malaria: the inhibition of viruses by artemisinin-type compounds. Biotechnol Adv 36:1730\u20131737. https:\/\/doi.org\/10.1016\/j.biotechadv.2018.01.001","journal-title":"Biotechnol Adv"},{"key":"3676_CR41","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1086\/591195","volume":"47","author":"T Efferth","year":"2008","unstructured":"Efferth T, Romero MR, Wolf DG, Stamminger T, Marin JJ, Marschall M (2008) The antiviral activities of artemisinin and artesunate. Clin Infect Dis 47:804\u2013811. https:\/\/doi.org\/10.1086\/591195","journal-title":"Clin Infect Dis"},{"key":"3676_CR42","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1073\/pnas.1413127112","volume":"112","author":"MA Elfawal","year":"2015","unstructured":"Elfawal MA, Towler MJ, Reich NG, Weathers PJ, Rich SM (2015) Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin. PNAS 112:821\u2013826. https:\/\/doi.org\/10.1073\/pnas.1413127112","journal-title":"PNAS"},{"key":"3676_CR43","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1126\/science.307.5706.33","volume":"307","author":"M Enserink","year":"2005","unstructured":"Enserink M (2005) Source of new hope against malaria is in short supply: new drugs based on an old Chinese cure could save countless lives in Africa, if health agencies and companies can find ways to make enough. Science 307:33","journal-title":"Science"},{"key":"3676_CR44","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.plantsci.2009.03.014","volume":"177","author":"LL Feng","year":"2009","unstructured":"Feng LL, Yang RY, Yang XQ, Zeng XM, Lu WJ, Zeng QP (2009) Synergistic re-channeling of mevalonate pathway for enhanced artemisinin production in transgenic Artemisia annua. Plant Sci 177:57\u201367. https:\/\/doi.org\/10.1016\/j.plantsci.2009.03.014","journal-title":"Plant Sci"},{"key":"3676_CR45","doi-asserted-by":"publisher","first-page":"397","DOI":"10.3390\/antibiotics4030397","volume":"4","author":"J Feng","year":"2015","unstructured":"Feng J, Weitner M, Shi W, Zhang S, Sullivan D, Zhang Y (2015) Identification of additional anti-persister activity against Borrelia burgdorferi from an FDA drug library. Antibiotics 4:397\u2013410. https:\/\/doi.org\/10.3390\/antibiotics4030397","journal-title":"Antibiotics"},{"key":"3676_CR46","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/BF00048526","volume":"44","author":"JFS Ferreira","year":"1996","unstructured":"Ferreira JFS, Janick J (1996) Roots as an enhancing factor for the production of artemisinin in shoot cultures of Artemisia annua. Plant Cell Tiss Org 44:211\u2013217. https:\/\/doi.org\/10.1007\/BF00048526","journal-title":"Plant Cell Tiss Org"},{"key":"3676_CR47","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1021\/jf903222j","volume":"58","author":"JFS Ferreira","year":"2010","unstructured":"Ferreira JFS, Luthria DL (2010) Drying affects artemisinin, dihydroartemisinic acid, artemisinic acid, and the antioxidant capacity of Artemisia annua L. leaves. J Agric Food Chem 58:1691\u20131698. https:\/\/doi.org\/10.1021\/jf903222j","journal-title":"J Agric Food Chem"},{"key":"3676_CR48","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1079\/PGR200585","volume":"3","author":"JFS Ferreira","year":"2005","unstructured":"Ferreira JFS, Laughlin J, Delabays N, De Magalh\u00e3es PM (2005) Cultivation and genetics of Artemisia annua L. for increased production of the antimalarial artemisinin. Plant Genet Resour 3:206\u2013229. https:\/\/doi.org\/10.1079\/PGR200585","journal-title":"Plant Genet Resour"},{"key":"3676_CR49","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.3389\/fpls.2018.01096","volume":"9","author":"JF Ferreira","year":"2018","unstructured":"Ferreira JF, Benedito VA, Sandhu D, Marchese JA, Liu S (2018) Seasonal and differential sesquiterpene accumulation in Artemisia annua suggest selection based on both artemisinin and dihydroartemisinic acid may increase artemisinin in planta. Front Plant Sci 9:1096","journal-title":"Front Plant Sci"},{"key":"3676_CR50","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.gene.2008.10.016","volume":"429","author":"OV Fursova","year":"2009","unstructured":"Fursova OV, Pogorelko GV, Tarasov VA (2009) Identification of ICE2, a gene involved in cold acclimation which determines freezing tolerance in Arabidopsis thaliana. Gene 429:98\u2013103. https:\/\/doi.org\/10.1016\/j.gene.2008.10.016","journal-title":"Gene"},{"key":"3676_CR51","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1126\/science.1182612","volume":"327","author":"IA Graham","year":"2010","unstructured":"Graham IA, Besser K, Blumer S, Branigan CA, Czechowski T, Elias L, Larson TR (2010) The genetic map of Artemisia annua L. identifies loci affecting yield of the antimalarial drug artemisinin. Science 327:328\u2013331. https:\/\/doi.org\/10.1126\/science.1182612","journal-title":"Science"},{"key":"3676_CR52","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1007\/s11101-019-09645-9","volume":"18","author":"BM Gruessner","year":"2019","unstructured":"Gruessner BM, Cornet-Vernet L, Desrosiers MR, Lutgen P, Towler MJ, Weathers PJ (2019) It is not just artemisinin: Artemisia sp. for treating diseases including malaria and schistosomiasis. Phytochem Rev 18:1509\u20131527. https:\/\/doi.org\/10.1007\/s11101-019-09645-9","journal-title":"Phytochem Rev"},{"key":"3676_CR53","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/s11274-016-2130-4","volume":"32","author":"R Gupta","year":"2016","unstructured":"Gupta R, Singh A, Gupta MM, Pandey R (2016) Cumulative role of bioinoculants on growth, antioxidant potential and artemisinin content in Artemisia annua L. under organic field conditions. World J Microb Biot 32:167. https:\/\/doi.org\/10.1007\/s11274-016-2130-4","journal-title":"World J Microb Biot"},{"key":"3676_CR54","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1093\/pcp\/pcz084","volume":"60","author":"X Hao","year":"2019","unstructured":"Hao X, Zhong Y, N\u00fctzmann HW, Fu X, Yan T, Shen Q, Tang K (2019) Light-induced artemisinin biosynthesis is regulated by the bZIP transcription factor AaHY5 in Artemisia annua. Plant Cell Physiol 60:1747\u20131760. https:\/\/doi.org\/10.1093\/pcp\/pcz084","journal-title":"Plant Cell Physiol"},{"key":"3676_CR55","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1111\/j.1365-2125.2006.02673.x","volume":"61","author":"E Hsu","year":"2006","unstructured":"Hsu E (2006) Reflections on the \u2018discovery\u2019of the antimalarial qinghao. Br J Clin Pharmacol 61:666\u2013670. https:\/\/doi.org\/10.1111\/j.1365-2125.2006.02673.x","journal-title":"Br J Clin Pharmacol"},{"key":"3676_CR56","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.3389\/fpls.2017.01966","volume":"8","author":"NK Ikram","year":"2017","unstructured":"Ikram NK, Simonsen HT (2017) A review of biotechnological artemisinin production in plants. Front Plant Sci 8:1966","journal-title":"Front Plant Sci"},{"key":"3676_CR57","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3389\/fbioe.2017.00047","volume":"5","author":"NKB Ikram","year":"2017","unstructured":"Ikram NKB, Kashkooli AB, Peramuna AV, van der Krol AR, Bouwmeester H, Simonsen HT (2017) Stable production of the antimalarial drug artemisinin in the Moss Physcomitrella patens. Front Bioeng Biotechnol 5:47. https:\/\/doi.org\/10.3389\/fbioe.2017.00047","journal-title":"Front Bioeng Biotechnol"},{"key":"3676_CR58","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1007\/s11240-017-1171-1","volume":"129","author":"P Inthima","year":"2017","unstructured":"Inthima P, Nakano M, Otani M, Niki T, Nishijima T, Koshioka M, Supaibulwatana K (2017) Overexpression of the gibberellin 20-oxidase gene from Torenia fournieri resulted in modified trichome formation and terpenoid metabolities of Artemisia annua L. Plant Cell Tissue Organ Cult 129:223\u2013236. https:\/\/doi.org\/10.1007\/s11240-017-1171-1","journal-title":"Plant Cell Tissue Organ Cult"},{"key":"3676_CR59","doi-asserted-by":"publisher","first-page":"1592","DOI":"10.1093\/pcp\/pcu090","volume":"55","author":"Y Ji","year":"2014","unstructured":"Ji Y, Xiao J, Shen Y, Ma D, Li Z, Pu G, Wang H (2014) Cloning and characterization of AabHLH1, a bHLH transcription factor that positively regulates artemisinin biosynthesis in Artemisia annua. Plant Cell Physiol 55:1592\u20131604. https:\/\/doi.org\/10.1093\/pcp\/pcu090","journal-title":"Plant Cell Physiol"},{"key":"3676_CR60","doi-asserted-by":"publisher","first-page":"319","DOI":"10.2478\/s11756-009-0040-8","volume":"64","author":"F Jing","year":"2009","unstructured":"Jing F, Zhang L, Li M, Tang Y, Wang Y, Wang Y, Tang K (2009) Abscisic acid (ABA) treatment increases artemisinin content in Artemisia annua by enhancing the expression of genes in artemisinin biosynthetic pathway. Biologia 64:319\u2013323. https:\/\/doi.org\/10.2478\/s11756-009-0040-8","journal-title":"Biologia"},{"key":"3676_CR61","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/j.molp.2019.02.011","volume":"12","author":"R Judd","year":"2019","unstructured":"Judd R, Bagley MC, Li M, Zhu Y, Lei C, Yuzuak S et al (2019) Artemisinin biosynthesis in non-glandular trichome cells of Artemisia annua. Mol Plant 12:704\u2013714. https:\/\/doi.org\/10.1016\/j.molp.2019.02.011","journal-title":"Mol Plant"},{"key":"3676_CR62","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s00572-007-0135-4","volume":"17","author":"R Kapoor","year":"2007","unstructured":"Kapoor R, Chaudhary V, Bhatnagar AK (2007) Effects of arbuscular mycorrhiza and phosphorus application on artemisinin concentration in Artemisia annua L. Mycorrhiza 17:581\u2013587. https:\/\/doi.org\/10.1007\/s00572-007-0135-4","journal-title":"Mycorrhiza"},{"key":"3676_CR63","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.1002\/bmc.3465","volume":"29","author":"S Khan","year":"2015","unstructured":"Khan S, Ali A, Ahmad S, Abdin MZ (2015) Affordable and rapid HPTLC method for the simultaneous analysis of artemisinin and its metabolite artemisinic acid in Artemisia annua L. Biomed Chromatogr 29:1594\u20131603. https:\/\/doi.org\/10.1002\/bmc.3465","journal-title":"Biomed Chromatogr"},{"key":"3676_CR64","doi-asserted-by":"publisher","DOI":"10.1093\/aobpla\/pls018","author":"A Kj\u00e6r","year":"2012","unstructured":"Kj\u00e6r A, Grevsen K, Jensen M (2012) Effect of external stress on density and size of glandular trichomes in full-grown Artemisia annua, the source of anti-malarial artemisinin. AoB Plants. https:\/\/doi.org\/10.1093\/aobpla\/pls018","journal-title":"AoB Plants"},{"key":"3676_CR65","doi-asserted-by":"publisher","first-page":"12028","DOI":"10.1088\/1755-1315\/482\/1\/012028","volume":"482","author":"S Koerniati","year":"2020","unstructured":"Koerniati S, Simanjuntak G (2020) CRISPR\/Cas9 system for disruption of biochemical pathway for sterol synthesis in Artemisia annua L. IOP Conf Series Earth Environ Sci 482:12028. https:\/\/doi.org\/10.1088\/1755-1315\/482\/1\/012028","journal-title":"IOP Conf Series Earth Environ Sci"},{"key":"3676_CR66","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/s1473-3099(03)00657-1","volume":"3","author":"EL Korenromp","year":"2003","unstructured":"Korenromp EL, Williams BG, Gouws E, Dye C, Snow RW (2003) Measurement of trends in childhood malaria mortality in Africa: an assessment of progress toward targets based on verbal autopsy. Lancet Infect Dis 3:349\u2013358. https:\/\/doi.org\/10.1016\/s1473-3099(03)00657-1","journal-title":"Lancet Infect Dis"},{"key":"3676_CR67","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1016\/j.jpba.2009.01.025","volume":"49","author":"AA Lapkin","year":"2009","unstructured":"Lapkin AA, Walker A, Sullivan N, Khambay B, Mlambo B, Chemat S (2009) Development of HPLC analytical protocols for quantification of artemisinin in biomass and extracts. J Pharmaceut Biomed 49:908\u2013915. https:\/\/doi.org\/10.1016\/j.jpba.2009.01.025","journal-title":"J Pharmaceut Biomed"},{"key":"3676_CR68","first-page":"67","volume":"390","author":"JC Laughlin","year":"1994","unstructured":"Laughlin JC (1994) The influence of distribution of antimalarial constituents in Artemisia annua L. on time and method of harvest. Internat Symp Med Aromat Plants 390:67\u201374","journal-title":"Internat Symp Med Aromat Plants"},{"key":"3676_CR69","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1002\/bab.1733","volume":"66","author":"L Li","year":"2019","unstructured":"Li L, Hao X, Liu H, Wang W, Fu X, Ma Y, Tang K (2019) Jasmonic acid-responsive AabHLH1 positively regulates artemisinin biosynthesis in Artemisia annua. Biotechnol Appl Biochem 66:369\u2013375. https:\/\/doi.org\/10.1002\/bab.1733","journal-title":"Biotechnol Appl Biochem"},{"key":"3676_CR70","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s00253-006-0452-0","volume":"72","author":"C Liu","year":"2006","unstructured":"Liu C, Zhao Y, Wang Y (2006) Artemisinin: current state and perspectives for biotechnological production of an antimalarial drug. Appl Microbiol Biot 72:11\u201320. https:\/\/doi.org\/10.1007\/s00253-006-0452-0","journal-title":"Appl Microbiol Biot"},{"key":"3676_CR71","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1002\/bab.1493","volume":"64","author":"W Liu","year":"2017","unstructured":"Liu W, Wang H, Chen Y, Zhu S, Chen M, Lan X, Liao Z (2017) Cold stress improves the production of artemisinin depending on the increase in endogenous jasmonate. Biotechnol Appl Bioc 64:305\u2013314. https:\/\/doi.org\/10.1002\/bab.1493","journal-title":"Biotechnol Appl Bioc"},{"key":"3676_CR72","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1104\/pp.15.00636","volume":"169","author":"LG Lowder","year":"2015","unstructured":"Lowder LG, Zhang D, Baltes NJ, Paul JW, Tang X, Zheng X, Voytas DF, Hsieh T, Zhang Y, Qi Y (2015) A CRISPR\/Cas9 toolbox for multiplexed plant genome editing and transcriptional regulation. Plant Physiol 169:971\u2013985","journal-title":"Plant Physiol"},{"key":"3676_CR73","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/med.2610070103","volume":"7","author":"XD Luo","year":"1987","unstructured":"Luo XD, Shen CC (1987) The chemistry, pharmacology, and clinical applications of qinghaosu (artemisinin) and its derivatives. Med Res Rev 7:29\u201352. https:\/\/doi.org\/10.1002\/med.2610070103","journal-title":"Med Res Rev"},{"key":"3676_CR74","doi-asserted-by":"publisher","first-page":"e1366398","DOI":"10.1080\/15592324.2017.1366398","volume":"12","author":"Z Lv","year":"2017","unstructured":"Lv Z, Zhang L, Tang K (2017) New insights into artemisinin regulation. Plant Signal Behav 12:e1366398. https:\/\/doi.org\/10.1080\/15592324.2017.1366398","journal-title":"Plant Signal Behav"},{"key":"3676_CR75","doi-asserted-by":"publisher","first-page":"3969","DOI":"10.1093\/jxb\/erz166","volume":"70","author":"Z Lv","year":"2019","unstructured":"Lv Z, Guo Z, Zhang L, Zhang F, Jiang W, Shen Q, Ma Y (2019) Interaction of bZIP transcription factor TGA6 with salicylic acid signaling modulates artemisinin biosynthesis in Artemisia annua. J Exp Bot 70:3969\u20133979. https:\/\/doi.org\/10.1093\/jxb\/erz166","journal-title":"J Exp Bot"},{"key":"3676_CR76","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s11306-009-0170-6","volume":"5","author":"C Ma","year":"2009","unstructured":"Ma C, Wang H, Lu X, Wang H, Xu G, Liu B (2009a) Terpenoid metabolic profiling analysis of transgenic Artemisia annua L. by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry. Metabolomics 5:497\u2013506. https:\/\/doi.org\/10.1007\/s11306-009-0170-6","journal-title":"Metabolomics"},{"key":"3676_CR77","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1093\/pcp\/pcp149","volume":"50","author":"D Ma","year":"2009","unstructured":"Ma D, Pu G, Lei C, Ma L, Wang H, Guo Y, Ye H (2009b) Isolation and characterization of AaWRKY1, an Artemisia annua transcription factor that regulates the amorpha-4, 11-diene synthase gene, a key gene of artemisinin biosynthesis. Plant Cell Physiol 50:2146\u20132161. https:\/\/doi.org\/10.1093\/pcp\/pcp149","journal-title":"Plant Cell Physiol"},{"key":"3676_CR78","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1016\/j.molp.2015.07.004","volume":"8","author":"DM Ma","year":"2015","unstructured":"Ma DM, Wang Z, Wang L, Alejos-Gonzales F, Sun MA, Xie DY (2015) A genome-wide scenario of terpene pathways in self-pollinated Artemisia annua. Mol Plant 8:1580\u20131598. https:\/\/doi.org\/10.1016\/j.molp.2015.07.004","journal-title":"Mol Plant"},{"key":"3676_CR79","doi-asserted-by":"publisher","first-page":"9357","DOI":"10.1126\/sciadv.aas9357","volume":"4","author":"YN Ma","year":"2018","unstructured":"Ma YN, Xu DB, Li L, Zhang F, Fu XQ, Shen Q, Hao XL (2018) Jasmonate promotes artemisinin biosynthesis by activating the TCP14-ORA complex in Artemisia annua. Sci Adv 4:9357. https:\/\/doi.org\/10.1126\/sciadv.aas9357","journal-title":"Sci Adv"},{"key":"3676_CR80","doi-asserted-by":"publisher","DOI":"10.1186\/s13020-020-00344-8","author":"T Ma","year":"2020","unstructured":"Ma T, Gao H, Zhang D, Shi Y, Zhang T, Shen X, Chen S (2020) Transcriptome analyses revealed the ultraviolet B irradiation and phytohormone gibberellins coordinately promoted the accumulation of artemisinin in Artemisia Annua L. Chinese Med. https:\/\/doi.org\/10.1186\/s13020-020-00344-8","journal-title":"Chinese Med"},{"key":"3676_CR81","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1111\/j.1469-8137.2010.03466.x","volume":"189","author":"L Maes","year":"2011","unstructured":"Maes L, Van Nieuwerburgh FC, Zhang Y, Reed DW, Pollier J, Vande Casteele SR, Inz\u00e9 D, Covello PS, Deforce DL, Goossens A (2011) Dissection of the phytohormonal regulation of trichome formation and biosynthesis of the antimalarial compound artemisinin in Artemisia annua plants. New Phytol 189:176\u2013189. https:\/\/doi.org\/10.1111\/j.1469-8137.2010.03466.x","journal-title":"New Phytol"},{"key":"3676_CR82","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00572-014-0614-3","volume":"25","author":"S Mandal","year":"2015","unstructured":"Mandal S, Upadhyay S, Wajid S, Ram M, Jain DC, Singh VP, Kapoor R (2015) Arbuscular mycorrhiza increase artemisinin accumulation in Artemisia annua by higher expression of key biosynthesis genes via enhanced jasmonic acid levels. Mycorrhiza 25:345\u2013357. https:\/\/doi.org\/10.1007\/s00572-014-0614-3","journal-title":"Mycorrhiza"},{"key":"3676_CR83","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s00299-009-0807-y","volume":"29","author":"A Mannan","year":"2010","unstructured":"Mannan A, Liu C, Arsenault PR, Towler MJ, Vail DR, Lorence A, Weathers PJ (2010) DMSO triggers the generation of ROS leading to an increase in artemisinin and dihydroartemisinic acid in Artemisia annua shoot cultures. Plant Cell Rep 29:143\u2013152. https:\/\/doi.org\/10.1007\/s00299-009-0807-y","journal-title":"Plant Cell Rep"},{"key":"3676_CR84","doi-asserted-by":"publisher","first-page":"113191","DOI":"10.1016\/j.jep.2020.113191","volume":"262","author":"MC Martini","year":"2020","unstructured":"Martini MC, Zhang T, Williams JT, Abramovitch R, Weathers PJ, Shell S (2020) Artemisia annua and Artemisia afra extracts exhibit strong bactericidal activity against Mycobacterium tuberculosis.\u00a0J Ethnopharmacol 262:113191","journal-title":"J Ethnopharmacol"},{"key":"3676_CR85","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/0378-1119(96)00054-6","volume":"172","author":"Y Matsushita","year":"1996","unstructured":"Matsushita Y, Kang W, Charlwood BV (1996) Cloning and analysis of a cDNA encoding farnesyl diphosphate synthase from Artemisia annua. Gene 172:207\u2013209. https:\/\/doi.org\/10.1016\/0378-1119(96)00054-6","journal-title":"Gene"},{"key":"3676_CR86","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1006\/abbi.2000.1962","volume":"381","author":"P Mercke","year":"2000","unstructured":"Mercke P, Bengtsson M, Bouwmeester HJ, Posthumus MA, Brodelius PE (2000) Molecular cloning, expression, and characterization of amorpha-4, 11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L. Arch Biochem Biophys 381:173\u2013180. https:\/\/doi.org\/10.1006\/abbi.2000.1962","journal-title":"Arch Biochem Biophys"},{"key":"3676_CR87","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1590\/0037-8682-0457-2016","volume":"50","author":"LE Mesa","year":"2017","unstructured":"Mesa LE, Vasquez D, Lutgen P, Restrepo AM, Ortiz I, Robledo SM (2017) In vitro and in vivo antileishmanial activity of Artemisia annua L. leaves powder and its potential usefulness in the treatment of uncomplicated cutaneous leishmaniasis in humans. Rev Soc Bras Med Trop 50:52\u201360. https:\/\/doi.org\/10.1590\/0037-8682-0457-2016","journal-title":"Rev Soc Bras Med Trop"},{"key":"3676_CR88","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.cell.2011.08.024","volume":"146","author":"LH Miller","year":"2011","unstructured":"Miller LH, Su X (2011) Artemisinin: discovery from the Chinese herbal garden. Cell 146:855\u2013858. https:\/\/doi.org\/10.1016\/j.cell.2011.08.024","journal-title":"Cell"},{"key":"3676_CR89","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.phymed.2018.10.014","volume":"51","author":"J Munyangi","year":"2018","unstructured":"Munyangi J, Cornet-Vernet L, Idumbo M, Chen L, Lutgen P, Perronne C, Ngombe N, Bianga J, Mupenda B, Lalukala P, Mergeai G, Mumba D, Towler MJ, Weathers PJ (2018) Effect of Artemisia annua and Artemisia afra tea infusions on schistosomiasis in a large clinical trial. Phytomedicine 51:233\u2013240. https:\/\/doi.org\/10.1016\/j.phymed.2018.10.014","journal-title":"Phytomedicine"},{"key":"3676_CR90","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.phymed.2018.12.002","volume":"57","author":"J Munyangi","year":"2019","unstructured":"Munyangi J, Cornet-Vernet L, Idumbo M, Chen L, Lutgen P, Perronne C, Ngombe N, Bianga J, Mupenda B, Lalukala P, Mergeai G, Mumba D, Towler MJ, Weathers PJ (2019) Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial. Phytomedicine 57:49\u201356. https:\/\/doi.org\/10.1016\/j.phymed.2018.12.002","journal-title":"Phytomedicine"},{"key":"3676_CR91","first-page":"19","volume":"7","author":"M Naeem","year":"2019","unstructured":"Naeem M, Aftab T, Ansari AA, Shabbir A, Khan MMA, Uddin M (2019) Arsenic exposure modulates physiological attributes and artemisinin biosynthesis in Artemisia annua L. Int J Herb Med 7:19\u201326","journal-title":"Int J Herb Med"},{"key":"3676_CR92","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s11816-010-0156-x","volume":"5","author":"T Nafis","year":"2011","unstructured":"Nafis T, Akmal M, Ram M, Alam P, Ahlawat S, Mohd A, Abdin MZ (2011) Enhancement of artemisinin content by constitutive expression of the HMG-CoA reductase gene in high-yielding strain of Artemisia annua L. Plant Biotechnol Rep 5:53\u201360. https:\/\/doi.org\/10.1007\/s11816-010-0156-x","journal-title":"Plant Biotechnol Rep"},{"key":"3676_CR93","doi-asserted-by":"publisher","first-page":"114016","DOI":"10.1016\/j.jep.2021.114016","volume":"274","author":"MS Nair","year":"2021","unstructured":"Nair MS, Huang Y, Fidock DA, Polyak SJ, Wagoner J, Towler MJ, Weathers PJ (2021) Artemisia annua L. extracts prevent in vitro replication of SARS-CoV-2 and two of its variants. J Ethnopharmacol 274:114016. https:\/\/doi.org\/10.1016\/j.jep.2021.114016","journal-title":"J Ethnopharmacol"},{"key":"3676_CR94","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.phymed.2018.06.002","volume":"47","author":"J Na\u00df","year":"2018","unstructured":"Na\u00df J, Efferth T (2018) The activity of Artemisia spp and their constituents against trypanosomiasis. Phytomedicine 47:184\u2013191. https:\/\/doi.org\/10.1016\/j.phymed.2018.06.002","journal-title":"Phytomedicine"},{"key":"3676_CR95","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s00299-012-1355-4","volume":"32","author":"KT Nguyen","year":"2013","unstructured":"Nguyen KT, Towler MJ, Weathers PJ (2013) The effect of roots and media constituents on trichomes and artemisinin production in Artemisia annua L. Plant Cell Rep 32:207\u2013218. https:\/\/doi.org\/10.1007\/s00299-012-1355-4","journal-title":"Plant Cell Rep"},{"key":"3676_CR96","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1016\/j.phytochem.2009.07.009","volume":"70","author":"ME Olsson","year":"2009","unstructured":"Olsson ME, Olofsson LM, Lindahl AL, Lundgren A, Brodelius M, Brodelius PE (2009) Localization of enzymes of artemisinin biosynthesis to the apical cells of glandular secretory trichomes of Artemisia annua L. Phytochemistry 70:1123\u20131128. https:\/\/doi.org\/10.1016\/j.phytochem.2009.07.009","journal-title":"Phytochemistry"},{"key":"3676_CR97","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.4172\/2167-0412.1000125","volume":"2","author":"M Onimus","year":"2013","unstructured":"Onimus M, Carteron S, Lutgen P (2013) The surprising efficiency of Artemisia annua powder capsules. Med Aromat Plants 2:2167\u20132412. https:\/\/doi.org\/10.4172\/2167-0412.1000125","journal-title":"Med Aromat Plants"},{"key":"3676_CR98","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1038\/nrmicro3240","volume":"12","author":"CJ Paddon","year":"2014","unstructured":"Paddon CJ, Keasling JD (2014) Semi-synthetic artemisinin: a model for the use of synthetic biology in pharmaceutical development. Nat Rev Microbiol 12:355\u2013367. https:\/\/doi.org\/10.1038\/nrmicro3240","journal-title":"Nat Rev Microbiol"},{"key":"3676_CR99","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1038\/nature12051","volume":"496","author":"CJ Paddon","year":"2013","unstructured":"Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496:528\u2013532. https:\/\/doi.org\/10.1038\/nature12051","journal-title":"Nature"},{"key":"3676_CR100","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1007\/s00299-009-0713-3","volume":"28","author":"GB Pu","year":"2009","unstructured":"Pu GB, Ma DM, Chen JL, Ma LQ, Wang H, Li GF, Liu BY (2009) Salicylic acid activates artemisinin biosynthesis in Artemisia annua L. Plant Cell Rep 28:1127\u20131135. https:\/\/doi.org\/10.1007\/s00299-009-0713-3","journal-title":"Plant Cell Rep"},{"key":"3676_CR101","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3389\/fpls.2016.00329","volume":"7","author":"G Pulice","year":"2016","unstructured":"Pulice G, Pelaz S, Mat\u00edas-Hern\u00e1ndez L (2016) Molecular farming in Artemisia annua, a promising approach to improve anti-malarial drug production. Front Plant Sci 7:329. https:\/\/doi.org\/10.3389\/fpls.2016.00329","journal-title":"Front Plant Sci"},{"key":"3676_CR102","unstructured":"Qian Z, Gong K, Zhang L, Lv J, Jing F, Wang Y, Tang K (2007) A simple and efficient procedure to enhance artemisinin content in Artemisia annua L. by seeding to salinity stress. Afr J Biotechnol 6."},{"key":"3676_CR103","doi-asserted-by":"publisher","first-page":"560","DOI":"10.3389\/fpls.2021.657156","volume":"12","author":"W Qin","year":"2021","unstructured":"Qin W, Xie L, Li Y, Liu H, Fu X, Chen T, Tang K (2021) An R2R3-MYB transcription factor positively regulates the glandular secretory trichome initiation in Artemisia annua L. Front Plant Sci 12:560. https:\/\/doi.org\/10.3389\/fpls.2021.657156","journal-title":"Front Plant Sci"},{"key":"3676_CR104","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.envexpbot.2004.03.014","volume":"53","author":"MI Qureshi","year":"2005","unstructured":"Qureshi MI, Israr M, Abdin MZ, Iqbal M (2005) Responses of Artemisia annua L. to lead and salt-induced oxidative stress. Environ Exp Bot 53:185\u2013193. https:\/\/doi.org\/10.1016\/j.envexpbot.2004.03.014","journal-title":"Environ Exp Bot"},{"key":"3676_CR105","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1007\/s11738-010-0470-5","volume":"32","author":"M Ram","year":"2010","unstructured":"Ram M, Khan MA, Jha P, Khan S, Kiran U, Ahmad MM, Abdin MZ (2010) HMG-CoA reductase limits artemisinin biosynthesis and accumulation in Artemisia annua L. plants. Acta Physiol Plant 32:859\u2013866. https:\/\/doi.org\/10.1007\/s11738-010-0470-5","journal-title":"Acta Physiol Plant"},{"key":"3676_CR106","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1038\/nature04640","volume":"440","author":"DK Ro","year":"2006","unstructured":"Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Chang MC (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940\u2013943. https:\/\/doi.org\/10.1038\/nature04640","journal-title":"Nature"},{"key":"3676_CR107","doi-asserted-by":"publisher","first-page":"12659","DOI":"10.1038\/s41598-018-31079-0","volume":"8","author":"M Salehi","year":"2018","unstructured":"Salehi M, Karimzadeh G, Naghavi MR, Badi HN, Monfared SR (2018) Expression of key genes affecting artemisinin content in five Artemisia species. Sci Rep 8:12659. https:\/\/doi.org\/10.1038\/s41598-018-31079-0","journal-title":"Sci Rep"},{"key":"3676_CR108","first-page":"1","volume":"37","author":"NS Sangwan","year":"2010","unstructured":"Sangwan NS, Kumar R, Srivastava S, Kumar A, Gupta A, Sangwan RS (2010) Recent developments on secondary metabolite biosynthesis in Artemisia annua L. J Plant Biol 37:1\u201324","journal-title":"J Plant Biol"},{"key":"3676_CR109","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.phytochem.2009.10.015","volume":"71","author":"N Schramek","year":"2010","unstructured":"Schramek N, Wang H, R\u00f6misch-Margl W, Keil B, Radykewicz T, Winzenh\u00f6rlein B, Liu B (2010) Artemisinin biosynthesis in growing plants of Artemisia annua. A 13CO2 study. Phytochemistry 71:179\u2013187. https:\/\/doi.org\/10.1016\/j.phytochem.2009.10.015","journal-title":"Phytochemistry"},{"key":"3676_CR110","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1111\/nph.13874","volume":"210","author":"Q Shen","year":"2016","unstructured":"Shen Q, Lu X, Yan T, Fu X, Lv Z, Zhang F, Tang K (2016) The jasmonate-responsive Aa MYC 2 transcription factor positively regulates artemisinin biosynthesis in Artemisia annua. New Phytol 210:1269\u20131281. https:\/\/doi.org\/10.1111\/nph.13874","journal-title":"New Phytol"},{"key":"3676_CR111","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/435713","author":"C Shi","year":"2015","unstructured":"Shi C, Li H, Yang Y, Hou L (2015) Anti-inflammatory and immunoregulatory functions of artemisinin and its derivatives. Med Inflamm. https:\/\/doi.org\/10.1155\/2015\/435713","journal-title":"Med Inflamm"},{"key":"3676_CR112","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/BF00024071","volume":"11","author":"A Shukla","year":"1992","unstructured":"Shukla A, Farooqi AA, Shukla YN, Sharma S (1992) Effect of triacontanol and chlormequat on growth, plant hormones and artemisinin yield in Artemisia annua L. Plant Growth Regul 11:165\u2013171. https:\/\/doi.org\/10.1007\/BF00024071","journal-title":"Plant Growth Regul"},{"key":"3676_CR113","doi-asserted-by":"publisher","first-page":"1034","DOI":"10.1111\/pbi.12476","volume":"14","author":"ND Singh","year":"2016","unstructured":"Singh ND, Kumar S, Daniell H (2016) Expression of \u03b2-glucosidase increases trichome density and artemisinin content in transgenic Artemisia annua plants. Plant Biotechnol J 14:1034\u20131045. https:\/\/doi.org\/10.1111\/pbi.12476","journal-title":"Plant Biotechnol J"},{"key":"3676_CR114","doi-asserted-by":"publisher","first-page":"161","DOI":"10.3390\/pr6090161","volume":"6","author":"M Sixt","year":"2018","unstructured":"Sixt M, Schmidt A, Mestm\u00e4cker F, Huter MJ, Uhlenbrock L, Strube J (2018) Systematic and model-assisted process design for the extraction and purification of Artemisinin from Artemisia annua L.\u2014Part I: conceptual process design and cost estimation. Processes 6:161. https:\/\/doi.org\/10.3390\/pr6090161","journal-title":"Processes"},{"key":"3676_CR115","first-page":"99","volume":"101","author":"LMJ Smith","year":"2010","unstructured":"Smith LMJ, Bentley S, Jones H, Burns C, Aroo RRJ, Woolley JG (2010) Developing an alternative UK industrial crop Artemisia annua, for the extraction of artemisinin to treat multi-drug resistant malaria. Asp Appl Biol 101:99\u2013106","journal-title":"Asp Appl Biol"},{"key":"3676_CR116","doi-asserted-by":"publisher","first-page":"113638","DOI":"10.1016\/j.jep.2020.113638","volume":"268","author":"D Snider","year":"2021","unstructured":"Snider D, Weathers PJ (2021) In vitro reduction of Plasmodium falciparum gametocytes: Artemisia spp tea infusions vs artemisinin. J Ethnopharmacol 268:113638. https:\/\/doi.org\/10.1016\/j.jep.2020.113638","journal-title":"J Ethnopharmacol"},{"key":"3676_CR117","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1002\/2211-5463.12184","volume":"7","author":"P Soni","year":"2017","unstructured":"Soni P, Abdin MZ (2017) Water deficit-induced oxidative stress affects artemisinin content and expression of proline metabolic genes in Artemisia annua L. FEBS Open Bio 7:367\u2013381. https:\/\/doi.org\/10.1002\/2211-5463.12184","journal-title":"FEBS Open Bio"},{"key":"3676_CR118","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1016\/j.jpba.2015.10.003","volume":"117","author":"J Suberu","year":"2016","unstructured":"Suberu J, Gromski PS, Nordon A, Lapkin A (2016) Multivariate data analysis and metabolic profiling of artemisinin and related compounds in high yielding varieties of Artemisia annua field-grown in Madagascar. J Pharm Biomed Anal 117:522\u2013531. https:\/\/doi.org\/10.1016\/j.jpba.2015.10.003","journal-title":"J Pharm Biomed Anal"},{"key":"3676_CR119","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-019-00678-2","author":"W Sun","year":"2019","unstructured":"Sun W, Han X, Wu S, Wu J, Yang C, Li X (2019) Unexpected mechanism of colitis amelioration by artesunate, a natural product from Artemisia annua L. Inflammopharmacology. https:\/\/doi.org\/10.1007\/s10787-019-00678-2","journal-title":"Inflammopharmacology"},{"key":"3676_CR120","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1007\/s00299-014-1566-y","volume":"33","author":"K Tang","year":"2014","unstructured":"Tang K, Shen Q, Yan T, Fu X (2014) Transgenic approach to increase artemisinin content in Artemisia annua L. Plant Cell Rep 33:605\u2013615. https:\/\/doi.org\/10.1007\/s00299-014-1566-y","journal-title":"Plant Cell Rep"},{"key":"3676_CR121","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1023\/A:1026430019738","volume":"226","author":"A Torelli","year":"2000","unstructured":"Torelli A, Trotta A, Acerbi I, Arcidiacono G, Berta G, Branca C (2000) IAA and ZR content in leek (Allium porrum L.) as influenced by P-nutrition and arbuscular mycorrhizae, in relation to plant development. Plant Soil 226:29\u201335. https:\/\/doi.org\/10.1023\/A:1026430019738","journal-title":"Plant Soil"},{"key":"3676_CR122","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1007\/s00299-007-0420-x","volume":"26","author":"MJ Towler","year":"2007","unstructured":"Towler MJ, Weathers PJ (2007) Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways. Plant Cell Rep 26:2129\u20132136. https:\/\/doi.org\/10.1007\/s00299-007-0420-x","journal-title":"Plant Cell Rep"},{"key":"3676_CR123","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.indcrop.2015.01.007","volume":"67","author":"MJ Towler","year":"2015","unstructured":"Towler MJ, Weathers PJ (2015) Variations in key artemisinic and other metabolites throughout plant development in a clonal cultivar of Artemisia annua for possible therapeutic use. Ind Crops Prod 67:185\u2013191. https:\/\/doi.org\/10.1016\/j.indcrop.2015.01.007","journal-title":"Ind Crops Prod"},{"key":"3676_CR124","doi-asserted-by":"publisher","first-page":"e61989","DOI":"10.1371\/journal.pone.0061989","volume":"8","author":"T Townsend","year":"2013","unstructured":"Townsend T, Segura V, Chigeza G, Penfield T, Rae A, Harvey D et al (2013) The use of combining ability analysis to identify elite parents for Artemisia annua F1 hybrid production. PLoS ONE 8:e61989. https:\/\/doi.org\/10.1371\/journal.pone.0061989","journal-title":"PLoS ONE"},{"key":"3676_CR125","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-018-21598-1","volume":"8","author":"D Vashisth","year":"2018","unstructured":"Vashisth D, Kumar R, Rastogi S, Patel VK, Kalra A, Gupta MM, Shasany AK (2018) Transcriptome changes induced by abiotic stresses in Artemisia annua. Sci Rep 8:1\u201314. https:\/\/doi.org\/10.1038\/s41598-018-21598-1","journal-title":"Sci Rep"},{"key":"3676_CR126","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1023\/A:1013786332363","volume":"23","author":"Y Wang","year":"2001","unstructured":"Wang Y, Zhang H, Zhao B, Yuan X (2001) Improved growth of Artemisia annua L. hairy roots and artemisinin production under red light conditions. Biotechnol Lett 23:1971\u20131973. https:\/\/doi.org\/10.1023\/A:1013786332363","journal-title":"Biotechnol Lett"},{"key":"3676_CR127","doi-asserted-by":"publisher","first-page":"3396","DOI":"10.5897\/JMPR.9000369","volume":"5","author":"Y Wang","year":"2011","unstructured":"Wang Y, Jing F, Yu S et al (2011) Co-overexpression of the HMGR and FPS genes enhances artemisinin content in Artemisia annua L. J Med Plants Res 5:3396\u20133403. https:\/\/doi.org\/10.5897\/JMPR.9000369","journal-title":"J Med Plants Res"},{"key":"3676_CR128","doi-asserted-by":"publisher","first-page":"1987","DOI":"10.1080\/00397911.2014.884225","volume":"44","author":"Z Wang","year":"2014","unstructured":"Wang Z, Yang L, Yang X, Zhang X (2014) Advances in the chemical synthesis of artemisinin. Synth Commun 44:1987\u20132003. https:\/\/doi.org\/10.1080\/00397911.2014.884225","journal-title":"Synth Commun"},{"key":"3676_CR129","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1007\/s00425-016-2560-0","volume":"244","author":"S Wang","year":"2016","unstructured":"Wang S, Towler MJ, Weathers PJ (2016) Root regulation of artemisinin production in Artemisia annua: trichome and metabolite evidence. Planta 244:999\u20131010. https:\/\/doi.org\/10.1007\/s00425-016-2560-0","journal-title":"Planta"},{"key":"3676_CR130","doi-asserted-by":"publisher","first-page":"358","DOI":"10.3389\/fpls.2018.00358","volume":"9","author":"HY Wetzstein","year":"2018","unstructured":"Wetzstein HY, Porter JA, Janick J, Ferreira JF, Mutui TM (2018) Selection and clonal propagation of high artemisinin genotypes of Artemisia annua. Front Plant Sci 9:358. https:\/\/doi.org\/10.3389\/fpls.2018.00358","journal-title":"Front Plant Sci"},{"key":"3676_CR131","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1126\/science.1155165","volume":"320","author":"NJ White","year":"2008","unstructured":"White NJ (2008) Qinghaosu (Artemisinin) the price of success. Science 320:331\u2013334. https:\/\/doi.org\/10.1126\/science.1155165","journal-title":"Science"},{"key":"3676_CR132","unstructured":"WHO (2006) WHO monograph on good agricultural and collection practices (GACP) for Artemisia annua L. World Health Organization."},{"key":"3676_CR133","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1080\/10826070701451555","volume":"30","author":"V Widmer","year":"2007","unstructured":"Widmer V, Handloser D, Reich E (2007) Quantitative HPTLC analysis of artemisinin in dried Artemisia annua L.: a practical approach. J Liq Chromatogr Relat Technol 30:2209\u20132219. https:\/\/doi.org\/10.1080\/10826070701451555","journal-title":"J Liq Chromatogr Relat Technol"},{"key":"3676_CR134","doi-asserted-by":"publisher","DOI":"10.1016\/j.plantsci.2021.110920","author":"Z Wu","year":"2021","unstructured":"Wu Z, Li L, Liu H, Yan X, Ma Y, Li Y, Tang K (2021) AaMYB15, an R2R3-MYB TF in Artemisia annua, acts as a negative regulator of artemisinin biosynthesis. Plant Sci. https:\/\/doi.org\/10.1016\/j.plantsci.2021.110920","journal-title":"Plant Sci"},{"key":"3676_CR135","first-page":"503","volume":"5","author":"L Xiang","year":"2012","unstructured":"Xiang L, Zeng L, Yuan Y, Chen M, Wang F, Liu X, Liao Z (2012) Enhancement of artemisinisn biosynthesis by overexpressing dxr, cyp71av1 and cpr in the plants of Artemisia annua L. Plant Omics 5:503","journal-title":"Plant Omics"},{"key":"3676_CR136","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s10725-014-0004-z","volume":"75","author":"L Xiang","year":"2015","unstructured":"Xiang L, Zhu S, Zhao T, Zhang M, Liu W, Chen M, Liao Z (2015) Enhancement of artemisinin content and relative expression of genes of artemisinin biosynthesis in Artemisia annua by exogenous MeJA treatment. Plant Growth Regul 75:435\u2013441. https:\/\/doi.org\/10.1007\/s10725-014-0004-z","journal-title":"Plant Growth Regul"},{"key":"3676_CR137","doi-asserted-by":"publisher","first-page":"4835","DOI":"10.1093\/jxb\/erz220","volume":"70","author":"L Xiang","year":"2019","unstructured":"Xiang L, Jian D, Zhang F, Yang C, Bai G, Lan X, Liao Z (2019) The cold-induced transcription factor bHLH112 promotes artemisinin biosynthesis indirectly via ERF1 in Artemisia annua. J Exp Bot 70:4835\u20134848. https:\/\/doi.org\/10.1093\/jxb\/erz220","journal-title":"J Exp Bot"},{"key":"3676_CR138","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1007\/s11101-016-9480-2","volume":"15","author":"DY Xie","year":"2016","unstructured":"Xie DY, Ma DM, Judd R, Jones AL (2016) Artemisinin biosynthesis in Artemisia annua and metabolic engineering: questions, challenges, and perspectives. Phytochem Rev 15:1093\u20131114. https:\/\/doi.org\/10.1007\/s11101-016-9480-2","journal-title":"Phytochem Rev"},{"key":"3676_CR139","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.plaphy.2013.10.023","volume":"74","author":"RK Yadav","year":"2014","unstructured":"Yadav RK, Sangwan RS, Sabir F, Srivastava AK, Sangwan NS (2014) Effect of prolonged water stress on specialized secondary metabolites, peltate glandular trichomes, and pathway gene expression in Artemisia annua L. Plant Physiol Biochem 74:70\u201383. https:\/\/doi.org\/10.1016\/j.plaphy.2013.10.023","journal-title":"Plant Physiol Biochem"},{"key":"3676_CR140","first-page":"608","volume":"45","author":"L Yan","year":"2003","unstructured":"Yan L, He-Chun Y, Hong W et al (2003) Molecular cloning, Escherichia coli expression and genomic organization of squalene synthase gene from Artemisia annua. Acta Bot Sin 45:608\u2013613","journal-title":"Acta Bot Sin"},{"key":"3676_CR141","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1055\/s-0029-1240620","volume":"76","author":"RY Yang","year":"2010","unstructured":"Yang RY, Zeng XM, Lu YY, Lu WJ, Feng LL, Yang XQ, Zeng QP (2010) Senescent leaves of Artemisia annua are one of the most active organs for overexpression of artemisinin biosynthesis responsible genes upon burst of singlet oxygen. Planta Med 76:734\u2013742. https:\/\/doi.org\/10.1055\/s-0029-1240620","journal-title":"Planta Med"},{"key":"3676_CR142","doi-asserted-by":"publisher","first-page":"7489","DOI":"10.1038\/s41598-017-07871-9","volume":"7","author":"H Yang","year":"2017","unstructured":"Yang H, Wu J, Tang T, Liu K, Dai C (2017) CRISPR\/Cas9-mediated genome editing efficiently creates specific mutations at multiple loci using one sgRNA in Brassica napus. Sci Rep 7:7489","journal-title":"Sci Rep"},{"key":"3676_CR143","unstructured":"Yin LL, Zhao C, Huang Y, Yang RY, Zeng QP (2008) Abiotic stress-induced expression of artemisinin biosynthesis genes in Artemisia annua L. \u61c9\u7528\u8207\u74b0\u5883\u751f\u7269\u5b78\u5831 14:1\u20135."},{"key":"3676_CR144","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1093\/mp\/ssr087","volume":"5","author":"ZX Yu","year":"2012","unstructured":"Yu ZX, Li JX, Yang CQ, Hu WL, Wang LJ, Chen XY (2012) The jasmonate-responsive AP2\/ERF transcription factors AaERF1 and AaERF2 positively regulate artemisinin biosynthesis in Artemisia annua L. Mol Plant 5:353\u2013365. https:\/\/doi.org\/10.1093\/mp\/ssr087","journal-title":"Mol Plant"},{"key":"3676_CR145","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14715\/cmb\/2018.64.9.1","volume":"64","author":"A Zebarjadi","year":"2018","unstructured":"Zebarjadi A, Dianatkhah S, Mohammadi PP, Qaderi A (2018) Influence of abiotic elicitors on improvement production of artemisinin in cell culture of Artemisia annua L. Cell Mol Biol 64:1\u20135","journal-title":"Cell Mol Biol"},{"key":"3676_CR146","doi-asserted-by":"publisher","DOI":"10.1016\/j.plaphy.2020.08.048","author":"A Zehra","year":"2020","unstructured":"Zehra A, Choudhary S, Wani KI, Naeem M, Khan MMA, Aftab T (2020) Exogenous abscisic acid mediates ROS homeostasis and maintains glandular trichome to enhance artemisinin biosynthesis in Artemisia annua under copper toxicity. Plant Physiol Biochem. https:\/\/doi.org\/10.1016\/j.plaphy.2020.08.048","journal-title":"Plant Physiol Biochem"},{"key":"3676_CR147","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.3978\/j.issn.2072-1439.2015.07.05","volume":"7","author":"AH Zeng","year":"2015","unstructured":"Zeng AH, Ou YY, Guo MM, Dai X, Zhou DZ, Chen R (2015) Human embryonic lung fibroblasts treated with artesunate exhibit reduced rates of proliferation and human cytomegalovirus infection in vitro. J Thorac Dis 7:1151\u20131157. https:\/\/doi.org\/10.3978\/j.issn.2072-1439.2015.07.05","journal-title":"J Thorac Dis"},{"key":"3676_CR148","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1042\/BA20080068","volume":"52","author":"L Zhang","year":"2009","unstructured":"Zhang L, Jing F, Li F, Li M, Wang Y, Wang G, Tang K (2009) Development of transgenic Artemisia annua (Chinese wormwood) plants with an enhanced content of artemisinin, an effective anti-malarial drug, by hairpin-RNA-mediated gene silencing. Biotechnol Appl Biochem 52:199\u2013207. https:\/\/doi.org\/10.1042\/BA20080068","journal-title":"Biotechnol Appl Biochem"},{"key":"3676_CR149","doi-asserted-by":"publisher","first-page":"e56697","DOI":"10.1371\/journal.pone.0056697","volume":"8","author":"F Zhang","year":"2013","unstructured":"Zhang F, Lu X, Lv Z, Zhang L, Zhu M, Jiang W, Tang K (2013) Overexpression of the Artemisia orthologue of ABA receptor, AaPYL9, enhances ABA sensitivity and improves artemisinin content in Artemisia annua L. PLoS ONE 8:e56697. https:\/\/doi.org\/10.1371\/journal.pone.0056697","journal-title":"PLoS ONE"},{"key":"3676_CR150","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.molp.2014.12.004","volume":"8","author":"F Zhang","year":"2015","unstructured":"Zhang F, Fu X, Lv Z, Lu X, Shen Q, Zhang L, Tang K (2015) A basic leucine zipper transcription factor, AabZIP1, connects abscisic acid signaling with artemisinin biosynthesis in Artemisia annua. Mol Plant 8:163\u2013175. https:\/\/doi.org\/10.1016\/j.molp.2014.12.004","journal-title":"Mol Plant"},{"key":"3676_CR151","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/nchembio.2259","volume":"13","author":"H Zheng","year":"2017","unstructured":"Zheng H, Colvin CJ, Johnson BK, Kirchhoff PD, Wilson M, Jorgensen-Muga K, Larsen SD, Abramovitch RB (2017) Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence. Nat Chem Biol 13:218. https:\/\/doi.org\/10.1038\/nchembio.2259","journal-title":"Nat Chem Biol"},{"key":"3676_CR152","doi-asserted-by":"publisher","first-page":"1777","DOI":"10.3389\/fpls.2018.01777","volume":"9","author":"Y Zhong","year":"2018","unstructured":"Zhong Y, Li L, Hao X, Fu X, Ma Y, Xie L, Tang K (2018) AaABF3, an abscisic acid\u2013responsive transcription factor, positively regulates artemisinin biosynthesis in Artemisia annua. Front Plant Sci 9:1777. https:\/\/doi.org\/10.3389\/fpls.2018.01777","journal-title":"Front Plant Sci"},{"key":"3676_CR153","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.biotechadv.2016.02.004","volume":"34","author":"M Zhou","year":"2016","unstructured":"Zhou M, Memelink J (2016) Jasmonate-responsive transcription factors regulating plant secondary metabolism. Biotechnol Adv 34:441\u2013449. https:\/\/doi.org\/10.1016\/j.biotechadv.2016.02.004","journal-title":"Biotechnol Adv"},{"key":"3676_CR154","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/s11684-016-0486-3","volume":"11","author":"L Zhou","year":"2017","unstructured":"Zhou L, Yang G, Sun H, Tang J, Yang J, Wang Y, Guo L (2017) Effects of different doses of cadmium on secondary metabolites and gene expression in Artemisia annua L. Front Med 11:137\u2013146. https:\/\/doi.org\/10.1007\/s11684-016-0486-3","journal-title":"Front Med"},{"key":"3676_CR155","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1111\/nph.16777","volume":"228","author":"Z Zhou","year":"2020","unstructured":"Zhou Z, Tan H, Li Q, Li Q, Wang Y, Bu Q, Zhang L (2020) Trichome and artemisinin regulator 2 positively regulates trichome development and artemisinin biosynthesis in Artemisia annua. New Phytol 228:932\u2013945. https:\/\/doi.org\/10.1111\/nph.16777","journal-title":"New Phytol"}],"container-title":["Planta"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00425-021-03676-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00425-021-03676-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00425-021-03676-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,7]],"date-time":"2025-04-07T16:07:03Z","timestamp":1744042023000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00425-021-03676-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,15]]},"references-count":155,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["3676"],"URL":"https:\/\/doi.org\/10.1007\/s00425-021-03676-3","relation":{},"ISSN":["0032-0935","1432-2048"],"issn-type":[{"value":"0032-0935","type":"print"},{"value":"1432-2048","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,15]]},"assertion":[{"value":"10 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"29"}}