{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T04:44:48Z","timestamp":1789533888727,"version":"build-2803163510"},"reference-count":137,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T00:00:00Z","timestamp":1665705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Project","award":["2017YFC1702800"],"award-info":[{"award-number":["2017YFC1702800"]}]},{"name":"National Key Research and Development Project","award":["2019YFC1708802"],"award-info":[{"award-number":["2019YFC1708802"]}]},{"name":"National Key Research and Development Project","award":["171100310500"],"award-info":[{"award-number":["171100310500"]}]},{"name":"National Key Research and Development Project","award":["ZYQR201810080"],"award-info":[{"award-number":["ZYQR201810080"]}]},{"name":"National Key Research and Development Project","award":["2021GGJS086"],"award-info":[{"award-number":["2021GGJS086"]}]},{"name":"Major Science and Technology Project in Henan Province","award":["2017YFC1702800"],"award-info":[{"award-number":["2017YFC1702800"]}]},{"name":"Major Science and Technology Project in Henan Province","award":["2019YFC1708802"],"award-info":[{"award-number":["2019YFC1708802"]}]},{"name":"Major Science and Technology Project in Henan Province","award":["171100310500"],"award-info":[{"award-number":["171100310500"]}]},{"name":"Major Science and Technology Project in Henan Province","award":["ZYQR201810080"],"award-info":[{"award-number":["ZYQR201810080"]}]},{"name":"Major Science and Technology Project in Henan Province","award":["2021GGJS086"],"award-info":[{"award-number":["2021GGJS086"]}]},{"name":"Henan Province High-Level Personnel Special Support \u201cZhongYuan One Thousand People Plan\u201d","award":["2017YFC1702800"],"award-info":[{"award-number":["2017YFC1702800"]}]},{"name":"Henan Province High-Level Personnel Special Support \u201cZhongYuan One Thousand People Plan\u201d","award":["2019YFC1708802"],"award-info":[{"award-number":["2019YFC1708802"]}]},{"name":"Henan Province High-Level Personnel Special Support \u201cZhongYuan One Thousand People Plan\u201d","award":["171100310500"],"award-info":[{"award-number":["171100310500"]}]},{"name":"Henan Province High-Level Personnel Special Support \u201cZhongYuan One Thousand People Plan\u201d","award":["ZYQR201810080"],"award-info":[{"award-number":["ZYQR201810080"]}]},{"name":"Henan Province High-Level Personnel Special Support \u201cZhongYuan One Thousand People Plan\u201d","award":["2021GGJS086"],"award-info":[{"award-number":["2021GGJS086"]}]},{"name":"Training Program for Young Teachers in Colleges and Universities of Henan Province","award":["2017YFC1702800"],"award-info":[{"award-number":["2017YFC1702800"]}]},{"name":"Training Program for Young Teachers in Colleges and Universities of Henan Province","award":["2019YFC1708802"],"award-info":[{"award-number":["2019YFC1708802"]}]},{"name":"Training Program for Young Teachers in Colleges and Universities of Henan Province","award":["171100310500"],"award-info":[{"award-number":["171100310500"]}]},{"name":"Training Program for Young Teachers in Colleges and Universities of Henan Province","award":["ZYQR201810080"],"award-info":[{"award-number":["ZYQR201810080"]}]},{"name":"Training Program for Young Teachers in Colleges and Universities of Henan Province","award":["2021GGJS086"],"award-info":[{"award-number":["2021GGJS086"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Malaria is a life-threatening disease. Artemisinin-based combination therapy (ACT) is the preferred choice for malaria treatment recommended by the World Health Organization. At present, the main source of artemisinin is extracted from Artemisia annua; however, the artemisinin content in A. annua is only 0.1\u20131%, which cannot meet global demand. Meanwhile, the chemical synthesis of artemisinin has disadvantages such as complicated steps, high cost and low yield. Therefore, the application of the synthetic biology approach to produce artemisinin in vivo has magnificent prospects. In this review, the biosynthesis pathway of artemisinin was summarized. Then we discussed the advances in the heterologous biosynthesis of artemisinin using microorganisms (Escherichia coli and Saccharomyces cerevisiae) as chassis cells. With yeast as the cell factory, the production of artemisinin was transferred from plant to yeast. Through the optimization of the fermentation process, the yield of artemisinic acid reached 25 g\/L, thereby producing the semi-synthesis of artemisinin. Moreover, we reviewed the genetic engineering in A. annua to improve the artemisinin content, which included overexpressing artemisinin biosynthesis pathway genes, blocking key genes in competitive pathways, and regulating the expression of transcription factors related to artemisinin biosynthesis. Finally, the research progress of artemisinin production in other plants (Nicotiana, Physcomitrella, etc.) was discussed. The current advances in artemisinin biosynthesis may help lay the foundation for the remarkable up-regulation of artemisinin production in A. annua through gene editing or molecular design breeding in the future.<\/jats:p>","DOI":"10.3390\/molecules27206888","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T03:43:58Z","timestamp":1665978238000},"page":"6888","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":66,"title":["From Plant to Yeast\u2014Advances in Biosynthesis of Artemisinin"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1213-1126","authenticated-orcid":false,"given":"Le","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P. R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhao","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P. R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Jia","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongguang","family":"Han","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P. R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Materials Engineering, Beijing Technology and Business University, Beijing 100048, China"},{"name":"Beijing Key Laboratory of Plant Research and Development, Beijing Technology and Business University, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisheng","family":"Feng","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Co-Construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan and Education Ministry of P. R. China, Henan University of Chinese Medicine, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11434-015-0929-2","article-title":"Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants","volume":"61","author":"Yang","year":"2016","journal-title":"Sci. Bull."},{"key":"ref_2","first-page":"1","article-title":"Plant terpenoids: Applications and future potentials","volume":"3","author":"Zwenger","year":"2008","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110457","DOI":"10.1016\/j.plantsci.2020.110457","article-title":"Advances in biosynthesis, regulation, and metabolic engineering of plant specialized terpenoids","volume":"294","author":"Nagegowda","year":"2020","journal-title":"Plant Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/bs.podrm.2018.11.001","article-title":"Chapter Three\u2014Paclitaxel","volume":"Volume 44","author":"Alqahtani","year":"2019","journal-title":"Profiles of Drug Substances, Excipients and Related Methodology"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hewlings, S.J., and Kalman, D.S. (2017). Curcumin: A review of its effects on human health. Foods, 6.","DOI":"10.3390\/foods6100092"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Khan, M., Ali, S., Manghwar, H., Saqib, S., Ullah, F., Ayaz, A., and Zaman, W. (2022). Melatonin function and crosstalk with other phytohormones under normal and stressful conditions. Genes, 13.","DOI":"10.3390\/genes13101699"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1038\/nm.2471","article-title":"The discovery of artemisinin (qinghaosu) and gifts from Chinese medicine","volume":"17","author":"Tu","year":"2011","journal-title":"Nat. Med."},{"key":"ref_8","unstructured":"World Health Organization (2021, December 06). World Malaria Report 2021. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2021."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1002\/med.21446","article-title":"Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action","volume":"37","author":"Wong","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cell.2016.11.010","article-title":"Artemisinins target GABAA receptor signaling and impair \u03b1 cell identity","volume":"168","author":"Li","year":"2017","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nchembio.2259","article-title":"Inhibitors of Mycobacterium tuberculosis DosRST signaling and persistence","volume":"13","author":"Zheng","year":"2017","journal-title":"Nat. Chem. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1055\/s-2000-11115","article-title":"Seasonal variation of artemisinin and its biosynthetic precursors in plants of Artemisia annua of different geographical origin: Proof for the existence of chemotypes","volume":"66","author":"Wallaart","year":"2000","journal-title":"Planta Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1021\/ja00341a054","article-title":"Total synthesis of qinghaosu","volume":"105","author":"Schmid","year":"1983","journal-title":"J. Am. Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100229","DOI":"10.1016\/j.xplc.2021.100229","article-title":"Synthetic biology of plant natural products: From pathway elucidation to engineered biosynthesis in plant cells","volume":"2","author":"Zhu","year":"2021","journal-title":"Plant Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1146\/annurev-arplant-050312-120116","article-title":"Network analysis of the MVA and MEP pathways for isoprenoid synthesis","volume":"64","author":"Coman","year":"2013","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1006\/abbi.2000.1962","article-title":"Molecular cloning, expression, and characterization of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L.","volume":"381","author":"Mercke","year":"2000","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/j.febslet.2006.01.065","article-title":"Artemisia annua L. (Asteraceae) trichome-specific cDNAs reveal CYP71AV1, a cytochrome P450 with a key role in the biosynthesis of the antimalarial sesquiterpene lactone artemisinin","volume":"580","author":"Teoh","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/nature04640","article-title":"Production of the antimalarial drug precursor artemisinic acid in engineered yeast","volume":"440","author":"Ro","year":"2006","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1139\/B09-032","article-title":"Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin biosynthesis in Artemisia annua","volume":"87","author":"Teoh","year":"2009","journal-title":"Botany"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"21501","DOI":"10.1074\/jbc.M803090200","article-title":"The molecular cloning of artemisinic aldehyde \u039411(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua","volume":"283","author":"Zhang","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.3389\/fpls.2017.01966","article-title":"A review of biotechnological artemisinin production in plants","volume":"8","author":"Ikram","year":"2017","journal-title":"Front. Plant Sci."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Al-Khayri, J.M., Sudheer, W.N., Lakshmaiah, V.V., Mukherjee, E., Nizam, A., Thiruvengadam, M., Nagella, P., Alessa, F.M., Al-Mssallem, M.Q., and Rezk, A.A. (2022). Biotechnological approaches for production of artemisinin, an anti-malarial drug from Artemisia annua L.. Molecules, 27.","DOI":"10.3390\/molecules27093040"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bryant, L., Flatley, B., Patole, C., Brown, G.D., and Cramer, R. (2015). Proteomic analysis of Artemisia annua\u2014Towards elucidating the biosynthetic pathways of the antimalarial pro-drug artemisinin. BMC Plant Biol., 15.","DOI":"10.1186\/s12870-015-0565-7"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.tplants.2021.10.006","article-title":"Twenty years of plant genome sequencing: Achievements and challenges","volume":"27","author":"Sun","year":"2022","journal-title":"Trends Plant Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nbt833","article-title":"Engineering a mevalonate pathway in Escherichia coli for production of terpenoids","volume":"21","author":"Martin","year":"2003","journal-title":"Nat. Biotechnol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1002\/bit.21017","article-title":"High-level production of amorpha-4,11-diene in a two-phase partitioning bioreactor of metabolically engineered Escherichia coli","volume":"95","author":"Newman","year":"2006","journal-title":"Biotechnol. Bioeng."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tsuruta, H., Paddon, C.J., Eng, D., Lenihan, J.R., Horning, T., Anthony, L.C., Regentin, R., Keasling, J.D., Renninger, N.S., and Newman, J.D. (2009). High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0004489"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/nchembio875","article-title":"Engineering Escherichia coli for production of functionalized terpenoids using plant P450s","volume":"3","author":"Chang","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.ymben.2008.07.007","article-title":"Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4,11-diene","volume":"11","author":"Anthony","year":"2009","journal-title":"Metab. Eng."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"E111","DOI":"10.1073\/pnas.1110740109","article-title":"Production of amorphadiene in yeast, and its conversion to dihydroartemisinic acid, precursor to the antimalarial agent artemisinin","volume":"109","author":"Westfall","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1038\/nature12051","article-title":"High-level semi-synthetic production of the potent antimalarial artemisinin","volume":"496","author":"Paddon","year":"2013","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1126\/science.1182612","article-title":"The genetic map of Artemisia annua L. identifies loci affecting yield of the antimalarial drug artemisinin","volume":"327","author":"Graham","year":"2010","journal-title":"Science"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.molp.2018.03.015","article-title":"The genome of Artemisia annua provides insight into the evolution of asteraceae family and artemisinin biosynthesis","volume":"11","author":"Shen","year":"2018","journal-title":"Mol. Plant"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1007\/s11738-010-0470-5","article-title":"HMG-CoA reductase limits artemisinin biosynthesis and accumulation in Artemisia annua L. plants","volume":"32","author":"Ram","year":"2010","journal-title":"Acta Physiol. Plant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s11816-010-0156-x","article-title":"Enhancement of artemisinin content by constitutive expression of the HMG-CoA reductase gene in high-yielding strain of Artemisia annua L.","volume":"5","author":"Nafis","year":"2011","journal-title":"Plant Biotechnol. Rep."},{"key":"ref_36","first-page":"503","article-title":"Enhancement of artemisinin biosynthesis by overexpressing dxr, cyp71av1 and cpr in the plants of Artemisia annua L.","volume":"5","author":"Xiang","year":"2012","journal-title":"Plant Omics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fpls.2017.00077","article-title":"Overexpression and suppression of Artemisia annua 4-Hydroxy-3-methylbut-2-enyl diphosphate reductase 1 gene (AaHDR1) differentially regulate artemisinin and terpenoid biosynthesis","volume":"8","author":"Ma","year":"2017","journal-title":"Front. Plant Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/tpj.13583","article-title":"Overexpression of a type-I isopentenyl pyrophosphate isomerase of Artemisia annua in the cytosol leads to high arteannuin B production and artemisinin increase","volume":"91","author":"Ma","year":"2017","journal-title":"Plant J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0378-1119(96)00054-6","article-title":"Cloning and analysis of a cDNA encoding farnesyl diphosphate synthase from Artemisia annua","volume":"172","author":"Matsushita","year":"1996","journal-title":"Gene"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/j.1744-7909.2006.00208.x","article-title":"Effects of overexpression of the endogenous farnesyl diphosphate synthase on the artemisinin content in Artemisia annua L.","volume":"48","author":"Han","year":"2006","journal-title":"J. Integr. Plant Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s11240-010-9775-8","article-title":"Overexpression of farnesyl pyrophosphate synthase (FPS) gene affected artemisinin content and growth of Artemisia annua L.","volume":"103","author":"Banyai","year":"2010","journal-title":"Plant Cell Tissue Organ Cult."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0168-9452(00)00217-X","article-title":"Expression of a chimeric farnesyl diphosphate synthase gene in Artemisia annua L. transgenic plants via Agrobacterium tumefaciens-mediated transformation","volume":"155","author":"Chen","year":"2000","journal-title":"Plant Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"619","DOI":"10.4236\/ajps.2011.24073","article-title":"Trichome-specific expression of amorpha-4,11-diene synthase, a key enzyme of artemisinin biosynthesis in Artemisia annua L., as reported by a promoter-GUS fusion","volume":"2","author":"Wang","year":"2011","journal-title":"Am. J. Plant Sci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1016\/j.molp.2022.05.013","article-title":"Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield","volume":"15","author":"Liao","year":"2022","journal-title":"Mol. Plant"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1007\/s11306-009-0170-6","article-title":"Terpenoid metabolic profiling analysis of transgenic Artemisia annua L. by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry","volume":"5","author":"Ma","year":"2009","journal-title":"Metabolomics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/bab.1234","article-title":"Overexpression of artemisinic aldehyde \u039411 (13) reductase gene\u2013enhanced artemisinin and its relative metabolite biosynthesis in transgenic Artemisia annua L.","volume":"62","author":"Yuan","year":"2015","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1007\/s00299-011-1099-6","article-title":"Over-expression of HMG-CoA reductase and amorpha-4,11-diene synthase genes in Artemisia annua L. and its influence on artemisinin content","volume":"30","author":"Alam","year":"2011","journal-title":"Plant Cell Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.molp.2016.03.004","article-title":"Promoting artemisinin biosynthesis in Artemisia annua plants by substrate channeling","volume":"9","author":"Han","year":"2016","journal-title":"Mol. Plant"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3298","DOI":"10.4238\/2012.September.12.13","article-title":"Overexpression of the cytochrome P450 monooxygenase (cyp71av1) and cytochrome P450 reductase (cpr) genes increased artemisinin content in Artemisia annua (Asteraceae)","volume":"11","author":"Shen","year":"2012","journal-title":"Genet. Mol. Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s11816-012-0262-z","article-title":"The stacked over-expression of FPS, CYP71AV1 and CPR genes leads to the increase of artemisinin level in Artemisia annua L.","volume":"7","author":"Chen","year":"2013","journal-title":"Plant Biotechnol. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s11240-017-1173-z","article-title":"Promotion of artemisinin content in Artemisia annua by overexpression of multiple artemisinin biosynthetic pathway genes","volume":"129","author":"Shi","year":"2017","journal-title":"Plant Cell Tissue Organ Cult."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1055\/s-0029-1185775","article-title":"Overexpression of the HMG-CoA reductase gene leads to enhanced artemisinin biosynthesis in transgenic Artemisia annua plants","volume":"75","author":"Aquil","year":"2009","journal-title":"Planta Med."},{"key":"ref_53","unstructured":"Tang, K., Shen, Q., Chen, Y., Wang, T., Wu, S., and Lu, X. (2015). Overexpression DBR2 Gene Increased Artemisinin Content in Artemisia annua L.. (CN201210014227), China Patent Application."},{"key":"ref_54","unstructured":"Tang, K., Chen, Y., Shen, Q., Wang, T., Wu, S., and Wang, G. (2012). Overexpression ALDH1 Gene Increased Artemisinin Content in Artemisia annua L.. (CN201210014242), China Patent Application."},{"key":"ref_55","first-page":"3396","article-title":"Co-overexpression of the HMGR and FPS genes enhances artemisinin content in Artemisia annua L.","volume":"5","author":"Wang","year":"2011","journal-title":"J. Med. Plants Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.indcrop.2013.04.045","article-title":"Promotion of artemisinin biosynthesis in transgenic Artemisia annua by overexpressing ADS, CYP71AV1 and CPR genes","volume":"49","author":"Lu","year":"2013","journal-title":"Ind. Crops Prod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/BA20080068","article-title":"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","volume":"52","author":"Zhang","year":"2009","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1055\/s-0030-1271038","article-title":"Artemisinin biosynthesis enhancement in transgenic Artemisia annua plants by downregulation of the \u03b2-caryophyllene synthase gene","volume":"77","author":"Chen","year":"2011","journal-title":"Planta Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1093\/pcp\/pcw014","article-title":"Branch pathway blocking in Artemisia annua is a useful method for obtaining high yield artemisinin","volume":"57","author":"Lv","year":"2016","journal-title":"Plant Cell Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s00299-014-1566-y","article-title":"Transgenic approach to increase artemisinin content in Artemisia annua L.","volume":"33","author":"Tang","year":"2014","journal-title":"Plant Cell Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/s00425-021-03676-3","article-title":"Enhancing artemisinin content in and delivery from Artemisia annua: A review of alternative, classical, and transgenic approaches","volume":"254","author":"Wani","year":"2021","journal-title":"Planta"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/S0031-9422(02)00265-0","article-title":"A cDNA clone for \u03b2-caryophyllene synthase from Artemisia annua","volume":"61","author":"Cai","year":"2002","journal-title":"Phytochemistry"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1055\/s-0030-1249930","article-title":"The molecular cloning of dihydroartemisinic aldehyde reductase and its implication in artemisinin biosynthesis in Artemisia annua","volume":"76","author":"Quax","year":"2010","journal-title":"Planta Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1016\/j.indcrop.2015.07.077","article-title":"Expression of artemisinin biosynthesis genes in eight Artemisia species at three developmental stages","volume":"76","author":"Ranjbar","year":"2015","journal-title":"Ind. Crops Prod."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.tplants.2010.02.006","article-title":"WRKY transcription factors","volume":"15","author":"Rushton","year":"2010","journal-title":"Trends Plant Sci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s42483-019-0022-x","article-title":"WRKY transcription factors: Evolution, binding, and action","volume":"1","author":"Chen","year":"2019","journal-title":"Phytopathol. Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1093\/pcp\/pcp149","article-title":"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","volume":"50","author":"Ma","year":"2009","journal-title":"Plant Cell Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7314971","DOI":"10.1155\/2016\/7314971","article-title":"Overexpression of AaWRKY1 leads to an enhanced content of artemisinin in Artemisia annua","volume":"2016","author":"Jiang","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1007\/s11240-021-02049-8","article-title":"AaWRKY4 upregulates artemisinin content through boosting the expressions of key enzymes in artemisinin biosynthetic pathway","volume":"146","author":"Huang","year":"2021","journal-title":"Plant Cell Tissue Organ Cult."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1111\/nph.17453","article-title":"AaWRKY9 contributes to light- and jasmonate-mediated to regulate the biosynthesis of artemisinin in Artemisia annua","volume":"231","author":"Fu","year":"2021","journal-title":"New Phytol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1038\/s41438-021-00652-6","article-title":"AaWRKY17, a positive regulator of artemisinin biosynthesis, is involved in resistance to Pseudomonas syringae in Artemisia annua","volume":"8","author":"Chen","year":"2021","journal-title":"Hortic. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1111\/nph.14373","article-title":"GLANDULAR TRICHOME-SPECIFIC WRKY 1 promotes artemisinin biosynthesis in Artemisia annua","volume":"214","author":"Chen","year":"2017","journal-title":"New Phytol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1111\/pbi.13561","article-title":"Jasmonate- and abscisic acid-activated AaGSW1-AaTCP15\/AaORA transcriptional cascade promotes artemisinin biosynthesis in Artemisia annua","volume":"19","author":"Ma","year":"2021","journal-title":"Plant Biotechnol. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/jxb\/eraa523","article-title":"The WRKY transcription factor AaGSW2 promotes glandular trichome initiation in Artemisia annua","volume":"72","author":"Xie","year":"2021","journal-title":"J. Exp. Bot."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.bbrc.2018.07.123","article-title":"Transcriptional regulation of bHLH during plant response to stress","volume":"503","author":"Sun","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1093\/pcp\/pcu090","article-title":"Cloning and characterization of AabHLH1, a bHLH transcription factor that positively regulates artemisinin biosynthesis in Artemisia annua","volume":"55","author":"Ji","year":"2014","journal-title":"Plant Cell Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/bab.1733","article-title":"Jasmonic acid-responsive AabHLH1 positively regulates artemisinin biosynthesis in Artemisia annua","volume":"66","author":"Li","year":"2019","journal-title":"Biotechnol. Appl. Biochem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1111\/nph.13874","article-title":"The jasmonate-responsive AaMYC2 transcription factor positively regulates artemisinin biosynthesis in Artemisia annua","volume":"210","author":"Shen","year":"2016","journal-title":"New Phytol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"4835","DOI":"10.1093\/jxb\/erz220","article-title":"The cold-induced transcription factor bHLH112 promotes artemisinin biosynthesis indirectly via ERF1 in Artemisia annua","volume":"70","author":"Xiang","year":"2019","journal-title":"J. Exp. Bot."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/mp\/ssr087","article-title":"The jasmonate-responsive AP2\/ERF transcription factors AaERF1 and AaERF2 positively regulate artemisinin biosynthesis in Artemisia annua L.","volume":"5","author":"Yu","year":"2012","journal-title":"Mol. Plant"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"885622","DOI":"10.3389\/fpls.2022.885622","article-title":"Basic helix-loop-helix transcription factors AabHLH2 and AabHLH3 function antagonistically with AaMYC2 and are negative regulators in artemisinin biosynthesis","volume":"13","author":"Shen","year":"2022","journal-title":"Front. Plant Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/nph.12207","article-title":"AaORA, a trichome-specific AP2\/ERF transcription factor of Artemisia annua, is a positive regulator in the artemisinin biosynthetic pathway and in disease resistance to Botrytis cinerea","volume":"198","author":"Lu","year":"2013","journal-title":"New Phytol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1016\/j.molp.2015.04.002","article-title":"TRICHOME AND ARTEMISININ REGULATOR 1 is required for trichome development and artemisinin biosynthesis in Artemisia annua","volume":"8","author":"Tan","year":"2015","journal-title":"Mol. Plant"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.molp.2014.12.004","article-title":"A basic leucine zipper transcription factor, AabZIP1, connects abscisic acid signaling with artemisinin biosynthesis in Artemisia annua","volume":"8","author":"Zhang","year":"2015","journal-title":"Mol. Plant"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/j.apsb.2021.09.026","article-title":"Molecular insights into AabZIP1-mediated regulation on artemisinin biosynthesis and drought tolerance in Artemisia annua","volume":"12","author":"Shu","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.3389\/fpls.2019.01294","article-title":"The transcription factor AabZIP9 positively regulates the biosynthesis of artemisinin in Artemisia annua","volume":"10","author":"Shen","year":"2019","journal-title":"Front. Plant Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1093\/pcp\/pcz084","article-title":"Light-induced artemisinin biosynthesis is regulated by the bZIP transcription factor AaHY5 in Artemisia annua","volume":"60","author":"Hao","year":"2019","journal-title":"Plant Cell Physiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.1093\/jxb\/erz166","article-title":"Interaction of bZIP transcription factor TGA6 with salicylic acid signaling modulates artemisinin biosynthesis in Artemisia annua","volume":"70","author":"Lv","year":"2019","journal-title":"J. Exp. Bot."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1111\/tpj.13509","article-title":"AaMYB1 and its orthologue AtMYB61 affect terpene metabolism and trichome development in Artemisia annua and Arabidopsis thaliana","volume":"90","author":"Jiang","year":"2017","journal-title":"Plant J."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/nph.14789","article-title":"The roles of AaMIXTA1 in regulating the initiation of glandular trichomes and cuticle biosynthesis in Artemisia annua","volume":"217","author":"Shi","year":"2018","journal-title":"New Phytol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/nph.16777","article-title":"TRICHOME AND ARTEMISININ REGULATOR 2 positively regulates trichome development and artemisinin biosynthesis in Artemisia annua","volume":"228","author":"Zhou","year":"2020","journal-title":"New Phytol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1111\/nph.17514","article-title":"An HD-ZIP-MYB complex regulates glandular secretory trichome initiation in Artemisia annua","volume":"231","author":"Xie","year":"2021","journal-title":"New Phytol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"657156","DOI":"10.3389\/fpls.2021.657156","article-title":"An R2R3-MYB transcription factor positively regulates the glandular secretory trichome initiation in Artemisia annua L.","volume":"12","author":"Qin","year":"2021","journal-title":"Front. Plant Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"110920","DOI":"10.1016\/j.plantsci.2021.110920","article-title":"AaMYB15, an R2R3-MYB TF in Artemisia annua, acts as a negative regulator of artemisinin biosynthesis","volume":"308","author":"Wu","year":"2021","journal-title":"Plant Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1111\/jipb.13258","article-title":"The transcription factors TLR1 and TLR2 negatively regulate trichome density and artemisinin levels in Artemisia annua","volume":"64","author":"Lv","year":"2022","journal-title":"J. Integr. Plant Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1007\/s00425-022-03892-5","article-title":"Isolation and characterization of AaZFP1, a C2H2 zinc finger protein that regulates the AaIPPI1 gene involved in artemisinin biosynthesis in Artemisia annua","volume":"255","author":"Deng","year":"2022","journal-title":"Planta"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"111172","DOI":"10.1016\/j.plantsci.2021.111172","article-title":"AaSPL9 affects glandular trichomes initiation by positively regulating expression of AaHD1 in Artemisia annua L.","volume":"317","author":"He","year":"2022","journal-title":"Plant Sci."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"982317","DOI":"10.3389\/fpls.2022.982317","article-title":"MADS-box gene AaSEP4 promotes artemisinin biosynthesis in Artemisia annua","volume":"13","author":"Chen","year":"2022","journal-title":"Front. Plant Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1007\/s00299-006-0204-8","article-title":"Role of DREB transcription factors in abiotic and biotic stress tolerance in plants","volume":"25","author":"Agarwal","year":"2006","journal-title":"Plant Cell Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1104\/pp.105.073783","article-title":"Genome-wide analysis of the ERF gene family in Arabidopsis and rice","volume":"140","author":"Nakano","year":"2006","journal-title":"Plant Physiol."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Song, X., Li, Y., and Hou, X. (2013). Genome-wide analysis of the AP2\/ERF transcription factor superfamily in Chinese cabbage (Brassica rapa ssp. pekinensis). BMC Genom., 14.","DOI":"10.1186\/1471-2164-14-573"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Lu, X., Jiang, W., Zhang, L., Zhang, F., Zhang, F., Shen, Q., Wang, G., and Tang, K. (2013). AaERF1 positively regulates the resistance to Botrytis cinerea in Artemisia annua. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0057657"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"eaas9357","DOI":"10.1126\/sciadv.aas9357","article-title":"Jasmonate promotes artemisinin biosynthesis by activating the TCP14-ORA complex in Artemisia annua","volume":"4","author":"Ma","year":"2018","journal-title":"Sci. Adv."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Wang, S., Zhang, X., Li, B., Zhao, X., Shen, Y., and Yuan, Z. (2022). Genome-wide identification and characterization of bZIP gene family and cloning of candidate genes for anthocyanin biosynthesis in pomegranate (Punica granatum). BMC Plant Biol., 22.","DOI":"10.1186\/s12870-022-03560-6"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.3389\/fpls.2020.01258","article-title":"Regulation mechanisms of plant basic leucine zippers to various abiotic stresses","volume":"11","author":"Yu","year":"2020","journal-title":"Front. Plant Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S1360-1385(01)02223-3","article-title":"bZIP transcription factors in Arabidopsis","volume":"7","author":"Jakoby","year":"2002","journal-title":"Trends Plant Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1723","DOI":"10.1074\/jbc.275.3.1723","article-title":"ABFs, a family of ABA-responsive element binding factors","volume":"275","author":"Choi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1096\/fasebj.8.2.8119490","article-title":"Plant bZIP proteins gather at ACGT elements","volume":"8","author":"Foster","year":"1994","journal-title":"FASEB J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"319","DOI":"10.2478\/s11756-009-0040-8","article-title":"Abscisic acid (ABA) treatment increases artemisinin content in Artemisia annua by enhancing the expression of genes in artemisinin biosynthetic pathway","volume":"64","author":"Jing","year":"2009","journal-title":"Biologia"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1007\/s00299-009-0713-3","article-title":"Salicylic acid activates artemisinin biosynthesis in Artemisia annua L.","volume":"28","author":"Pu","year":"2009","journal-title":"Plant Cell Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.tplants.2010.06.005","article-title":"MYB transcription factors in Arabidopsis","volume":"15","author":"Dubos","year":"2010","journal-title":"Trends Plant Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.pbi.2009.07.015","article-title":"One, two, three\u2026 models for trichome patterning in Arabidopsis?","volume":"12","author":"Pesch","year":"2009","journal-title":"Curr. Opin. Plant Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/pbi.13448","article-title":"R2R3 MYB-dependent auxin signalling regulates trichome formation, and increased trichome density confers spider mite tolerance on tomato","volume":"19","author":"Yuan","year":"2021","journal-title":"Plant Biotechnol. J."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1111\/j.1365-313X.2008.03564.x","article-title":"MYBL2 is a new regulator of flavonoid biosynthesis in Arabidopsis thaliana","volume":"55","author":"Dubos","year":"2008","journal-title":"Plant J."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Zhang, L., Liu, Y., Shang, X., and Fang, S. (2022). Identification and expression analysis of R2R3-MYB family genes associated with salt tolerance in Cyclocarya paliurus. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23073429"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.tplants.2020.01.001","article-title":"Parallel transcriptional regulation of artemisinin and flavonoid biosynthesis","volume":"25","author":"Hassani","year":"2020","journal-title":"Trends Plant Sci."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.tibtech.2020.11.012","article-title":"Engineering metabolism in Nicotiana species: A promising future","volume":"39","author":"Demurtas","year":"2021","journal-title":"Trends Biotech."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1007\/s004250000428","article-title":"Amorpha-4,11-diene synthase: Cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisinin","volume":"212","author":"Wallaart","year":"2001","journal-title":"Planta"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/j.1467-7652.2010.00556.x","article-title":"The production of artemisinin precursors in tobacco","volume":"9","author":"Zhang","year":"2011","journal-title":"Plant Biotechnol. J."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1038\/nbt.2054","article-title":"Generation of the potent anti-malarial drug artemisinin in tobacco","volume":"29","author":"Farhi","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Van Herpen, T.W.J.M., Cankar, K., Nogueira, M., Bosch, D., Bouwmeester, H.J., and Beekwilder, J. (2010). Nicotiana benthamiana as a production platform for artemisinin precursors. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014222"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/nph.12274","article-title":"The metabolite chemotype of Nicotiana benthamiana transiently expressing artemisinin biosynthetic pathway genes is a function of CYP71AV1 type and relative gene dosage","volume":"199","author":"Ting","year":"2013","journal-title":"New Phytol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.ymben.2016.07.004","article-title":"Transient production of artemisinin in Nicotiana benthamiana is boosted by a specific lipid transfer protein from A. annua","volume":"38","author":"Wang","year":"2016","journal-title":"Metab. Eng."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s12038-013-9402-z","article-title":"Metabolic engineering of chloroplasts for artemisinic acid biosynthesis and impact on plant growth","volume":"39","author":"Saxena","year":"2014","journal-title":"J. Biosci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"e13664","DOI":"10.7554\/eLife.13664","article-title":"A new synthetic biology approach allows transfer of an entire metabolic pathway from a medicinal plant to a biomass crop","volume":"5","author":"Fuentes","year":"2016","journal-title":"eLife"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1016\/j.molp.2016.09.013","article-title":"Compartmentalized metabolic engineering for artemisinin biosynthesis and effective malaria treatment by oral delivery of plant cells","volume":"9","author":"Malhotra","year":"2016","journal-title":"Mol. Plant"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3389\/fbioe.2017.00047","article-title":"Stable production of the antimalarial drug artemisinin in the moss Physcomitrella patens","volume":"5","author":"Peramuna","year":"2017","journal-title":"Front. Bioeng. Biotech."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Ikram, N.K., Kashkooli, A.B., Peramuna, A., Krol, A.R.v.d., Bouwmeester, H., and Simonsen, H.T. (2019). Insights into heterologous biosynthesis of arteannuin B and artemisinin in Physcomitrella patens. Molecules, 24.","DOI":"10.3390\/molecules24213822"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Firsov, A., Pushin, A., Motyleva, S., Pigoleva, S., Shaloiko, L., Vainstein, A., and Dolgov, S. (2021). Heterologous biosynthesis of artemisinin in Chrysanthemum morifolium Ramat. Separations, 8.","DOI":"10.3390\/separations8060075"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1007\/s00299-018-2293-6","article-title":"Physcomitrella patens, a versatile synthetic biology chassis","volume":"37","author":"Reski","year":"2018","journal-title":"Plant Cell Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1126\/science.1150646","article-title":"The Physcomitrella genome reveals evolutionary insights into the conquest of land by plants","volume":"319","author":"Rensing","year":"2008","journal-title":"Science"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1111\/tpj.13801","article-title":"The Physcomitrella patens chromosome-scale assembly reveals moss genome structure and evolution","volume":"93","author":"Lang","year":"2018","journal-title":"Plant J."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"25030","DOI":"10.1038\/srep25030","article-title":"In vivo assembly of DNA-fragments in the moss, Physcomitrella patens","volume":"6","author":"King","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1111\/pbi.12401","article-title":"Moss-made pharmaceuticals: From bench to bedside","volume":"13","author":"Reski","year":"2015","journal-title":"Plant Biotechnol. J."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s11248-009-9252-5","article-title":"Production of taxa-4(5),11(12)-diene by transgenic Physcomitrella patens","volume":"18","author":"Anterola","year":"2009","journal-title":"Transgenic Res."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Yang, L., Nuerbiye, A., Cheng, P., Wang, J.H., and Li, H. (2017). Analysis of floral volatile components and antioxidant activity of different varieties of Chrysanthemum morifolium. Molecules, 22.","DOI":"10.3390\/molecules22101790"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Firsov, A., Mitiouchkina, T., Shaloiko, L., Pushin, A., Vainstein, A., and Dolgov, S. (2020). Agrobacterium-mediated transformation of Chrysanthemum with artemisinin biosynthesis pathway genes. Plants, 9.","DOI":"10.3390\/plants9040537"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6888\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:53:53Z","timestamp":1760144033000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/20\/6888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,14]]},"references-count":137,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["molecules27206888"],"URL":"https:\/\/doi.org\/10.3390\/molecules27206888","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,14]]}}}