Skip to main content
SpringerLink
Log in

Transgenic approach to increase artemisinin content in Artemisia annua L.

  • Review
  • Published:
Plant Cell Reports Aims and scope Submit manuscript

Abstract

Artemisinin, the endoperoxide sesquiterpene lactone, is an effective antimalarial drug isolated from the Chinese medicinal plant Artemisia annua L. Due to its effectiveness against multi-drug-resistant cerebral malaria, it becomes the essential components of the artemisinin-based combination therapies which are recommended by the World Health Organization as the preferred choice for malaria tropica treatments. To date, plant A. annua is still the main commercial source of artemisinin. Although semi-synthesis of artemisinin via artemisinic acid in yeast is feasible at present, another promising approach to reduce the price of artemisinin is using plant metabolic engineering to obtain a higher content of artemisinin in transgenic plants. In the past years, an Agrobacterium-mediated transformation system of A. annua has been established by which a number of genes related to artemisinin biosynthesis have been successfully transferred into A. annua plants. In this review, the progress on increasing artemisinin content in A. annua by transgenic approach and its future prospect are summarized and discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Alam P, Abdin MZ (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 30:1919–1928

    Article  PubMed  CAS  Google Scholar 

  • Anthony JR, Anthony LC, Nowroozi F, Kwon G, Newman JD, Keasling JD (2009) Optimization of the mevalonate-based isoprenoid biosynthetic pathway in Escherichia coli for production of the anti-malarial drug precursor amorpha-4, 11-diene. Metab Eng 11:13–19

    Article  PubMed  CAS  Google Scholar 

  • Aquil S, Husaini AM, Abdin MZ, Rather GM (2009) Overexpression of the HMG-CoA reductase gene leads to enhanced artemisinin biosynthesis in transgenic Artemisia annua plants. Planta Med 75:1453–1458

    Article  PubMed  CAS  Google Scholar 

  • Arsenault PR, Wobbe KK, Weathers PJ (2008) Recent advances in artemisinin production through heterologous expression. Curr Med Chem 15:2886

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Arsenault PR, Vail DR, Wobbe KK, Erickson K, Weathers PJ (2010) Reproductive development modulates gene expression and metabolite levels with possible feedback inhibition of artemisinin in Artemisia annua L. Plant Physiol 154:958–968

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Avery MA, Chong WK, Jennings-White C (1992) Stereoselective total synthesis of (+)-artemisinin, the antimalarial constituent of Artemisia annua L. J Am Chem Soc 114:974–979

    Article  CAS  Google Scholar 

  • Banyai W, Kirdmanee C, Mii M, Supaibulwatana K (2010) Overexpression of farnesyl pyrophosphate synthase (FPS) gene affected artemisinin content and growth of Artemisia annua L. Plant Cell Tiss Org Cult 103:255–265

    Article  CAS  Google Scholar 

  • Banyai W, Mii M, Supaibulwatana K (2011) Enhancement of artemisinin content and biomass in Artemisia annua by exogenous GA3 treatment. Plant Growth Regul 63:45–54

    Article  CAS  Google Scholar 

  • Barbacka K, Baer-Dubowska W (2011) Searching for artemisinin production improvement in plants and microorganisms. Curr Pharm Biotechnol 12:1743–1751

    Article  PubMed  CAS  Google Scholar 

  • Bouwmeester HJ, Wallaart TE, Janssen MH, van Loo B, Jansen BJ, Posthumus MA, Schmidt CO, De Kraker JW, König WA, Franssen MC (1999) Amorpha-4,11-diene synthase catalyses the first probable step in artemisinin biosynthesis. Phytochemistry 52:843–854

    Article  PubMed  CAS  Google Scholar 

  • Brown GD, Sy L-K (2004) In vivo transformations of dihydroartemisinic acid in Artemisia annua plants. Tetrahedron 60:1139–1159

    Article  CAS  Google Scholar 

  • Cai Y, Jia J-W, Crock J, Lin Z-X, Chen X-Y, Croteau R (2002) A cDNA clone for β-caryophyllene synthase from Artemisia annua. Phytochemistry 61:523–529

    Article  PubMed  CAS  Google Scholar 

  • Caretto S, Quarta A, Durante M, Nisi R, De Paolis A, Blando F, Mita G (2011) Methyl jasmonate and miconazole differently affect arteminisin production and gene expression in Artemisia annua suspension cultures. Plant Biol 13:51–58

    Article  PubMed  CAS  Google Scholar 

  • Carretero-Paulet L, Ahumada I, Cunillera N, Rodríguez-Concepción M, Ferrer A, Boronat A, Campos N (2002) Expression and molecular analysis of the Arabidopsis DXR gene encoding 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the first committed enzyme of the 2-C-methyl-d-erythritol 4-phosphate pathway. Plant Physiol 129:1581–1591

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Chatterjee M, Sharma P, Khurana JP (2006) Cryptochrome 1 from Brassica napus is up-regulated by blue light and controls hypocotyl/stem growth and anthocyanin accumulation. Plant Physiol 141:61–74

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • 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 155:179–185

    Article  PubMed  CAS  Google Scholar 

  • 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 beta-caryophyllene synthase gene. Planta Med 77:1759–1765

    Article  PubMed  CAS  Google Scholar 

  • Chen Y, Shen Q, Wang Y, Wang T, Wu S, Zhang L, Lu X, Zhang F, Jiang W, Qiu B, Gao E, Sun X, Tang K (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 7:287–295

    Article  Google Scholar 

  • Chini A, Boter M, Solano R (2009) Plant oxylipins: COI1/JAZs/MYC2 as the core jasmonic acid-signalling module. FEBS J 276:4682–4692

    Article  PubMed  CAS  Google Scholar 

  • Constantino MG, Beltrame M Jr, da Silva GVJ, Zukerman-Schpector J (1996) A novel asymmetric total synthesis of (+)-artemisinin. Synthetic Commun 26:321–329

    Article  CAS  Google Scholar 

  • Croteau R, Kutchan TM, Lewis NG (2000) Natural products (secondary metabolites). Biochemistry and molecular biology of plants. In: Buchanan E, Gruissem W, Jones R (eds) Wiley, pp 1250–1318

  • 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 155:365–372

    Article  Google Scholar 

  • Galis I, Gaquerel E, Pandey SP, Baldwin IT (2009) Molecular mechanisms underlying plant memory in JA-mediated defence responses. Plant Cell Environ 32:617–627

    Article  PubMed  CAS  Google Scholar 

  • Giliberto L, Perrotta G, Pallara P, Weller JL, Fraser PD, Bramley PM, Fiore A, Tavazza M, Giuliano G (2005) Manipulation of the blue light photoreceptor cryptochrome 2 in tomato affects vegetative development, flowering time, and fruit antioxidant content. Plant Physiol 137:199–208

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Graham IA, Besser K, Blumer S, Branigan CA, Czechowski T, Elias L, Guterman I, Harvey D, Isaac PG, Khan AM, Larson TR, Li Y, Pawson T, Penfield T, Rae AM, Rathbone DA, Reid S, Ross J, Smallwood MF, Segura V, Townsend T, Vyas D, Winzer T, Bowles D (2010) The genetic map of Artemisia annua L. identifies loci affecting yield of the antimalarial drug artemisinin. Science 327:328–331

    Article  PubMed  CAS  Google Scholar 

  • Han JL, Liu BY, Ye HC, Wang H, Li ZQ, Li GF (2006) Effects of overexpression of the endogenous farnesyl diphosphate synthase on the artemisinin content in Artemisia annua L. J Integr Plant Biol 48:482–487

    Article  CAS  Google Scholar 

  • Hong GJ, Hu WL, Li JX, Chen XY, Wang LJ (2009) Increased accumulation of artemisinin and anthocyanins in Artemisia annua expressing the Arabidopsis blue light receptor CRY1. Plant Mol Biol Rep 27:334–341

    Article  CAS  Google Scholar 

  • Jiang W, Lu X, Qiu B, Zhang F, Shen Q, Lv Z, Fu X, Yan T, Gao E, Zhu M (2013) Molecular cloning and characterization of a trichome-specific promoter of artemisinic aldehyde Δ11 (13) reductase (DBR2) in Artemisia annua. Plant Mol Biol Rep. doi:10.1007/s11105-013-0603-2

    Google Scholar 

  • Jing F, Zhang L, Li M, Tang Y, Wang Y, Wang Q, Pan Q, Wang G, Tang K (2009) Abscisic acid (ABA) treatment increases artemisinin content in Artemisia annua by enhancing the expression of genes in artemisinin biosynthetic pathway. Biologia 64:319–323

    Article  CAS  Google Scholar 

  • Kim SH, Chang YJ, Kim SU (2008) Tissue specificity and developmental pattern of amorpha-4,11-diene synthase (ADS) proved by ADS promoter-driven GUS expression in the heterologous plant, Arabidopsis thaliana. Planta Med 74:188–193

    Article  PubMed  CAS  Google Scholar 

  • Kumar S, Gupta S, Singh P, Bajpai P, Gupta M, Singh D, Gupta A, Ram G, Shasany A, Sharma S (2004) High yields of artemisinin by multi-harvest of Artemisia annua crops. Ind Crop Prod 19:77–90

    Article  CAS  Google Scholar 

  • Liu Y, Ye HC, Wang H, Li GF (2003) Molecular cloning, Escherichia coli expression and genomic organization of squalene synthase gene from Artemisia annua. Acta Bot Sin 45:608–613

    CAS  Google Scholar 

  • Lommen W, Schenk E, Bouwmeester H, Verstappen F (2006) Trichome dynamics and artemisinin accumulation during development and senescence of Artemisia annua leaves. Planta Med 72:336–345

    Article  PubMed  CAS  Google Scholar 

  • Lu X, Lin X, Shen Q, Zhang F, Wang Y, Chen Y, Wang T, Wu S, Tang K (2011) Characterization of the jasmonate biosynthetic gene allene oxide cyclase in Artemisia annua L., source of the antimalarial drug artemisinin. Plant Mol Biol Rep 29:489–497

    Article  CAS  Google Scholar 

  • Lu X, Shen Q, Zhang L, Zhang F, Jiang W, Lv Z, Yan T, Fu X, Wang G, Tang K (2013a) Promotion of artemisinin biosynthesis in transgenic Artemisia annua by overexpressing ADS, CYP71AV1 and CPR genes. Ind Crop Prod 49:380–385

    Article  CAS  Google Scholar 

  • Lu X, Zhang L, Zhang F, Jiang W, Shen Q, Zhang L, Lv Z, Wang G, Tang K (2013b) 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. New Phytol 198:1191–1202

    Article  PubMed  CAS  Google Scholar 

  • 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 5:497–506

    Article  CAS  Google Scholar 

  • Ma DM, Pu GB, Lei CY, Ma LQ, Wang HH, Guo YW, Chen JL, Du ZG, Wang H, Li GF, Ye HC, Liu BY (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 50:2146–2161

    Article  PubMed  CAS  Google Scholar 

  • Maes L, Goossens A (2010) Hormone-mediated promotion of trichome initiation in plants is conserved but utilizes species and trichome-specific regulatory mechanisms. Plant Signal Behav 5:205–207

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Maes L, Van Nieuwerburgh FCW, Zhang YS, Reed DW, Pollier J, Casteele S, Inze D, Covello PS, Deforce DLD, Goossens A (2011) Dissection of the phytohormonal regulation of trichome formation and biosynthesis of the antimalarial compound artemisinin in Artemisia annua plants. New Phytol 189:176–189

    Article  PubMed  CAS  Google Scholar 

  • Mannan A, Liu CZ, 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 29:143–152

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • 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 381:173–180

    Article  PubMed  CAS  Google Scholar 

  • Mutabingwa TK (2005) Artemisinin-based combination therapies (ACTS): best hope for malaria treatment but inaccessible to the needy! Acta Trop 95:305–315

    Article  PubMed  CAS  Google Scholar 

  • 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 5:53–60

    Article  Google Scholar 

  • Newman JD, Chappell J (1999) Isoprenoid biosynthesis in plants: carbon partitioning within the cytoplasmic pathway. Crit Rev Biochem Mol 34:95–106

    Article  CAS  Google Scholar 

  • Nguyen KT, Arsenault PR, Weathers PJ (2011) Trichomes + roots + ROS = artemisinin: regulating artemisinin biosynthesis in Artemisia annua L. In Vitro Cell Dev Biol-Plant 47:329–338

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Olofsson L, Engstrom A, Lundgren A, Brodelius PE (2011) Relative expression of genes of terpene metabolism in different tissues of Artemisia annua L. BMC Plant Biol 11:45

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Olofsson L, Lundgren A, Brodelius PE (2012) Trichome isolation with and without fixation using laser microdissection and pressure catapulting followed by RNA amplification: expression of genes of terpene metabolism in apical and sub-apical trichome cells of Artemisia annua L. Plant Sci 183:9–13

    Article  PubMed  CAS  Google Scholar 

  • Paddon CJ, Westfall PJ, Pitera DJ, Benjamin K, Fisher K, McPhee D, Leavell MD, Tai A, Main A, Eng D, Polichuk DR, Teoh KH, Reed DW, Treynor T, Lenihan J, Fleck M, Bajad S, Dang G, Dengrove D, Diola D, Dorin G, Ellens KW, Fickes S, Galazzo J, Gaucher SP, Geistlinger T, Henry R, Hepp M, Horning T, Iqbal T, Jiang H, Kizer L, Lieu B, Melis D, Moss N, Regentin R, Secrest S, Tsuruta H, Vazquez R, Westblade LF, Xu L, Yu M, Zhang Y, Zhao L, Lievense J, Covello PS, Keasling JD, Reiling KK, Renninger NS, Newman JD (2013) High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496:528–532

    Article  PubMed  CAS  Google Scholar 

  • Pan QF, Wang Q, Yuan F, Xing SH, Zhao JY, Choi Y, Verpoorte R, Tian YJ, Wang G, Tang KX (2012) Overexpression of ORCA3 and G10H in Catharanthus roseus plants regulated alkaloid biosynthesis and metabolism revealed by NMR-metabolomics. PLoS One 7:e43038

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Pu GB, Ma DM, Chen JL, Ma LQ, Wang H, Li GF, Ye HC, Liu BY (2009) Salicylic acid activates artemisinin biosynthesis in Artemisia annua L. Plant Cell Rep 28:1127–1135

    Article  PubMed  CAS  Google Scholar 

  • Ram M, Khan MA, Jha P, Khan S, Kiran U, Ahmad MM, Javed S, Abdin MZ (2010) HMG-CoA reductase limits artemisinin biosynthesis and accumulation in Artemisia annua L. plants. Acta Physiol Plant 32:859–866

    Article  CAS  Google Scholar 

  • Ro DK, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang CMJ, Withers ST, Shibata D, Sarpong R, Keasling JD (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440:940–943

    Article  PubMed  CAS  Google Scholar 

  • Ro DK, Ouellet M, Paradise EM, Burd H, Eng D, Paddon CJ, Newman JD, Keasling JD (2008) Induction of multiple pleiotropic drug resistance genes in yeast engineered to produce an increased level of anti-malarial drug precursor, artemisinic acid. BMC Biotechnol 8:83

    Article  PubMed Central  PubMed  Google Scholar 

  • Rodríguez-Concepción M, Forés O, Martínez-García JF, González V, Phillips MA, Ferrer A, Boronat A (2004) Distinct light-mediated pathways regulate the biosynthesis and exchange of isoprenoid precursors during Arabidopsis seedling development. Plant Cell 16:144–156

    Article  PubMed Central  PubMed  Google Scholar 

  • Schramek N, Wang HH, Romisch-Margl W, Keil B, Radykewicz T, Winzenhorlein B, Beerhues L, Bacher A, Rohdich F, Gershenzon J, Liu BY, Eisenreich W (2010) Artemisinin biosynthesis in growing plants of Artemisia annua. A 13CO2 study. Phytochemistry 71:179–187

    Article  PubMed  CAS  Google Scholar 

  • Shen Q, Chen YF, Wang T, Wu SY, Lu X, Zhang L, Zhang FY, Jiang WM, Wang GF, Tang KX (2012) Overexpression of the cytochrome P450 monooxygenase (cyp71av1) and cytochrome P450 reductase (cpr) genes increased artemisinin content in Artemisia annua (Asteraceae). Genet Mol Res 11:3298–3309

    Article  PubMed  CAS  Google Scholar 

  • Srivastava N, Akhila A (2011) Biosynthesis of artemisinin––revisited. J Plant Interact 6:265–273

    Article  CAS  Google Scholar 

  • Sy L-K, Brown GD (2002) The mechanism of the spontaneous autoxidation of dihydroartemisinic acid. Tetrahedron 58:897–908

    Article  CAS  Google Scholar 

  • Tang KX, Jiang WM, Lu X, Qiu B, Wang GF (2012a) Overexpression AaWRYK1 gene increased artemisinin content in Artemisia annua L. Shanghai Jiao Tong University, China. Patent CN201210249469.X, 14 Novemb 2012

  • Tang KX, Shen Q, Chen YF, Wang T, Wu SY, Lu X (2012b) Overexpression DBR2 gene increased artemisinin content in Artemisia annua L. Shanghai Jiao Tong University, China. Patent CN201210014227.2, 19 Sept 2012

  • Tang KX, Chen YF, Shen Q, Wang T, Wu SY, Wang GF (2012c) Overexpression ALDH1 gene increased artemisinin content in Artemisia annua L. Shanghai Jiao Tong University, China. Patent CN201210014242.7, 22 August 2012

  • Teoh KH, Polichuk DR, Reed DW, Nowak G, Covello PS (2006) 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. FEBS Lett 580:1411–1416

    Article  PubMed  CAS  Google Scholar 

  • Teoh KH, Polichuk DR, Reed DW, Covello PS (2009) Molecular cloning of an aldehyde dehydrogenase implicated in artemisinin biosynthesis in Artemisia annua. Botany 87:635–642

    Article  CAS  Google Scholar 

  • Towler MJ, Weathers PJ (2007) Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways. Plant Cell Rep 26:2129–2136

    Article  PubMed  CAS  Google Scholar 

  • Tsuruta H, Paddon CJ, Eng D, Lenihan JR, Horning T, Anthony LC, Regentin R, Keasling JD, Renninger NS, Newman JD (2009) High-level production of amorpha-4,11-diene, a precursor of the antimalarial agent artemisinin, in Escherichia coli. PLoS One 4:e4489

    Article  PubMed Central  PubMed  Google Scholar 

  • van der Fits L, Memelink J (2000) ORCA3, a jasmonate-responsive transcriptional regulator of plant primary and secondary metabolism. Science 289:295–297

    Article  PubMed  Google Scholar 

  • van der Fits L, Memelink J (2001) The jasmonate-inducible AP2/ERF-domain transcription factor ORCA3 activates gene expression via interaction with a jasmonate-responsive promoter element. Plant J 25:43–53

    Article  PubMed  Google Scholar 

  • Verpoorte R, Memelink J (2002) Engineering secondary metabolite production in plants. Curr Opin Biotech 13:181–187

    Article  PubMed  CAS  Google Scholar 

  • Wang HH, Ma CF, Li ZQ, Ma LQ, Wang H, Ye HC, Xu GW, Liu BY (2010) Effects of exogenous methyl jasmonate on artemisinin biosynthesis and secondary metabolites in Artemisia annua L. Ind Crop Prod 31(2):214–218

    Article  Google Scholar 

  • Wang HZ, Olofsson L, Lundgren A, Brodelius PE (2011a) 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. Am J Plant Sci 2:619–628

    Article  CAS  Google Scholar 

  • Wang YY, Yang K, Deng T, Huang R, Wang B, Wang GF, Sun XF, Tang KX (2011b) Cloning and characterization of trichome-specific promoter of cpr71av1 gene involved in artemisinin biosynthesis in Artemisia annua L. Mol Biol 145:751–758

    Article  Google Scholar 

  • Wang YY, Jing FY, Yu SY, Chen YF, Wang T, Liu P, Wang GF, Sun XF, Tang KX (2011c) Co-overexpression of the HMGR and FPS genes enhances artemisinin content in Artemisia annua L. J Med Plants Res 5:3396–3403

    CAS  Google Scholar 

  • Wang HZ, Han JL, Kanagarajan S, Lundgren A, Brodelius PE (2013) Trichome-specific expression of the amorpha-4,11-diene 12-hydroxylase (cyp71av1) gene, encoding a key enzyme of artemisinin biosynthesis in Artemisia annua, as reported by a promoter-GUS fusion. Plant Mol Biol 81:119–138

    Article  PubMed  CAS  Google Scholar 

  • Wasternack C, Kombrink E (2010) Jasmonates: structural requirements for lipid-derived signals active in plant stress responses and development. ACS Chem Biol 5:63–77

    Article  PubMed  CAS  Google Scholar 

  • Weathers PJ, Elkholy S, Wobbe KK (2006) Artemisinin: the biosynthetic pathway and its regulation in Artemisia annua, a terpenoid-rich species. In Vitro Cell Dev-Plant 42:309–317

    Article  CAS  Google Scholar 

  • Weathers PJ, Arsenault PR, Covello PS, McMickle A, Teoh KH, Reed DW (2011) Artemisinin production in Artemisia annua: studies in planta and results of a novel delivery method for treating malaria and other neglected diseases. Phytochem Rev 10:173–183

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Xiang LE, Zeng LX, Yuan Y, Chen M, Wang F, Liu XQ, Zeng LJ, Lan XZ, Liao ZH (2012) Enhancement of artemisinin biosynthesis by overexpressing dxr, cyp71av1 and cpr in the plants of Artemisia annua L. Plant Omics J 5:503–507

    CAS  Google Scholar 

  • 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 5:353–365

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Teoh KH, Reed DW, Maes L, Goossens A, Olson DJH, Ross ARS, Covello PS (2008) The molecular cloning of artemisinic aldehyde Δ11(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua. J Biol Chem 283:21501–21508

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Jing FY, Li FP, Li MY, Wang YL, Wang GF, Sun XF, Tang KX (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 52:199–207

    Article  PubMed  CAS  Google Scholar 

  • Zhang F, Lu X, Lv Z, Zhang L, Zhu M, Jiang W, Wang G, Sun X, 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

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zhu JK (2002) Salt and drought stress signal transduction in plants. Annu Rev Plant Biol 53:247

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zhu C, Cook SP (2012) A concise synthesis of (+)-artemisinin. J Am Chem Soc 134:13577–13579

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was funded by China national High-Tech “863” Program (grant no.2011AA100605), China Transgenic Research Program (grant no. 2013ZX08002-001) and Shanghai Leading Academic Discipline Project (Horticulture).

Author information

Authors and Affiliations

  1. Key Laboratory of Urban Agriculture (South) Ministry of Agriculture, Plant Biotechnology Research Center, Fudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China

    Kexuan Tang, Qian Shen, Tingxiang Yan & Xueqing Fu

Authors
  1. Kexuan Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qian Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tingxiang Yan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xueqing Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kexuan Tang.

Additional information

Communicated by N. Stewart.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tang, K., Shen, Q., Yan, T. et al. Transgenic approach to increase artemisinin content in Artemisia annua L.. Plant Cell Rep 33, 605–615 (2014). https://doi.org/10.1007/s00299-014-1566-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00299-014-1566-y

Keywords

Search

Navigation