Skip to main content

Advertisement

SpringerLink
Log in

Metabolic engineering of the anthocyanin biosynthetic pathway in Artemisia annua and relation to the expression of the artemisinin biosynthetic pathway

  • Original Article
  • Published:
Planta Aims and scope Submit manuscript

Abstract

Main conclusion

Four types of cells were engineered from Artemisia annua to produce approximately 17 anthocyanins, four of which were elucidated structurally. All of them expressed the artemisinin pathway.

Abstract

Artemisia annua is the only medicinal crop to produce artemisinin for the treatment of malignant malaria. Unfortunately, hundreds of thousands of people still lose their life every year due to the lack of sufficient artemisinin. Artemisinin is considered to result from the spontaneous autoxidation of dihydroartemisinic acid in the presence of reactive oxygen species (ROS) in an oxidative condition of glandular trichomes (GTs); however, whether increasing antioxidative compounds can inhibit artemisinin biosynthesis in plant cells is unknown. Anthocyanins are potent antioxidants that can remove ROS in plant cells. To date, no anthocyanins have been structurally elucidated from A. annua. In this study, we had two goals: (1) to engineer anthocyanins in A. annua cells and (2) to understand the artemisinin biosynthesis in anthocyanin-producing cells. Arabidopsis Production of Anthocyanin Pigment 1 was used to engineer four types of transgenic anthocyanin-producing A. annua (TAPA1–4) cells. Three wild-type cell types were developed as controls. TAPA1 cells produced the highest contents of total anthocyanins. LC–MS analysis detected 17 anthocyanin or anthocyanidin compounds. Crystallization, LC/MS/MS, and NMR analyses identified cyanidin, pelargonidin, one cyanin, and one pelargonin. An integrative analysis characterized that four types of TAPA cells expressed the artemisinin pathway and TAPA1 cells produced the highest artemisinin and artemisinic acid. The contents of arteannuin B were similar in seven cell types. These data showed that the engineering of anthocyanins does not eliminate the biosynthesis of artemisinin in cells. These data allow us to propose a new hypothesis that enzymes catalyze the formation of artemisinin from dihydroartemisinic acid in non-GT cells. These findings show a new platform to increase artemisinin production via non-GT cells of A. annua.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

All data that support our findings reported in this study are available in the supplementary materials of this article.

Abbreviations

ACT:

Artemisinin-based combination therapy

DHAA:

Dihydroartemisinic acid

GT:

Glandular trichome

HPLC–ESI-QTOF–MS:

High-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry

NMR:

Nuclear magnetic resonance

PAP1:

Production of anthocyanin pigmentation 1

qRT-PCR:

Quantitative reverse transcription-polymerase chain reaction

TAPA:

Transgenic anthocyanin-producing Artemisia annua calli

References

  • 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(4):685–697. https://doi.org/10.1007/s00425-011-1430-z

    Article  CAS  PubMed  Google Scholar 

  • Bishayee A, Haznagy-Radnai E, Mbimba T, Sipos P, Morazzoni P, Darvesh AS, Bhatia D, Hohmann J (2010) Anthocyanin-rich black currant extract suppresses the growth of human hepatocellular carcinoma cells. Nat Prod Commun 5(10):1613–1618

    CAS  PubMed  Google Scholar 

  • Borevitz JO, Xia Y, Blount J, Dixon RA, Lamb C (2000) Activation tagging identifies a conserved MYB regulator of phenylpropanoid biosynthesis. Plant Cell 12(12):2383–2394. https://doi.org/10.1105/tpc.12.12.2383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Broeckling C, Li K-G, Xie D (2012) Comparative metabolomics of transgenic tobacco plants (Nicotiana tabacum var. Xanthi) reveals differential effects of engineered complete and incomplete flavonoid pathways on the metabolome. In: Transgenic plants—advances and limitations

  • Brown GD (2010) The biosynthesis of artemisinin (Qinghaosu) and the phytochemistry of Artemisia annua L. (Qinghao). Molecules 15(11):7603–7698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Covello PS, Teoh KH, Polichuk DR, Reed DW, Nowak G (2007) Functional genomics and the biosynthesis of artemisinin. Phytochemistry 68(14):1864–1971

    Article  CAS  PubMed  Google Scholar 

  • Czechowski T, Larson TR, Catania TM, Harvey D, Brown GD, Graham IA (2016) Artemisia annua mutant impaired in artemisinin synthesis demonstrates importance of nonenzymatic conversion in terpenoid metabolism. PNAS 113(52):15150–15155. https://doi.org/10.1073/pnas.1611567113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Czechowski T, Branigan C, Rae A, Rathbone D, Larson TR, Harvey D, Catania TM, Zhang D, Li Y, Salmon M, Bowles DJ, O’Maille P, Graham IA (2022) Artemisia annua L. plants lacking bornyl diphosphate synthase reallocate carbon from monoterpenes to sesquiterpenes except artemisinin. Front Plant Sci. https://doi.org/10.3389/fpls.2022.1000819

    Article  PubMed  PubMed Central  Google Scholar 

  • Duke MV, Paul RN, Elsohly HN, Sturtz G, Duke SO (1994a) Localization of artemisinin and artemisitene in foliar tissues of glanded and glandless biotypes of Artemisia annua L. Int J Plant Sci 155(3):365–372

    Article  Google Scholar 

  • Duke MV, Paul RN, Elsohly HN, Sturtz G, Duke SO (1994b) Localization of artemisinin and artemisitene in foliar tissues of glanded and glandless biotypes of Artemisia annua L. Int J Plant Sci 155(3):365–372

    Article  Google Scholar 

  • Fan LL, Lin L, Zhang Y, Li SN, Tang ZH (2023) Component characteristics and reactive oxygen species scavenging activity of anthocyanins from fruits of Lonicera caerulea L. Food Chem. https://doi.org/10.1016/j.foodchem.2022.134391

    Article  PubMed  Google Scholar 

  • Gatica-Arias A, Farag M, Stanke M, Matoušek J, Wessjohann L, Weber G (2012) Flavonoid production in transgenic hop (Humulus lupulus L.) altered by PAP1/MYB75 from Arabidopsis thaliana L. Plant Cell Rep 31(1):111–119

    Article  CAS  PubMed  Google Scholar 

  • Graham IA, Besser K, Blumer S, Branigan CA, Czechowski T, Elias L, Guterman I, Harvey D, Isaac PG, Khan AM (2010) The genetic map of Artemisia annua L. identifies loci affecting yield of the antimalarial drug artemisinin. Science 327(5963):328–331

    Article  CAS  PubMed  Google Scholar 

  • Hatier J-HB, Gould KS (2008) Foliar anthocyanins as modulators of stress signals. J Theoretical Biol 253(3):625–627

    Article  CAS  Google Scholar 

  • He X, Li Y, Lawson D, Xie DY (2017) Metabolic engineering of anthocyanins in dark tobacco varieties. Physiol Plant 159(1):2–12

    Article  CAS  PubMed  Google Scholar 

  • Holton TA, Cornish EC (1995) Genetics and biochemistry of anthocyanin biosynthesis. Plant Cell 7(7):1071–1083

    Article  CAS  PubMed  PubMed Central  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(3):334–341. https://doi.org/10.1007/s11105-008-0088-6

    Article  CAS  Google Scholar 

  • Judd R, Bagley MC, Li MZ, Zhu Y, Lei CY, Yuzuak S, Ekelof M, Pu GB, Zhao XT, Muddiman DC, Xie DY (2019) Artemisinin biosynthesis in non-glandular trichome cells of Artemisia annua. Mol Plant 12(5):704–714. https://doi.org/10.1016/j.molp.2019.02.011

    Article  CAS  PubMed  Google Scholar 

  • Kano M, Takayanagi T, Harada K, Makino K, Ishikawa F (2005) Antioxidative activity of anthocyanins from purple sweet potato, Ipomoera batatas cultivar ayamurasaki. Biosci Biotechnol Biochem 69(5):979–988

    Article  CAS  PubMed  Google Scholar 

  • Kayani SI, Shen Q, Rahman SU, Fu XQ, Li YP, Wang C, Hassani D, Tang KX (2021) Transcriptional regulation of flavonoid biosynthesis in Artemisia annua by AaYABBY5. Hortic Res-Engl. https://doi.org/10.1038/s41438-021-00693-x

    Article  Google Scholar 

  • Khusnutdinov E, Sukhareva A, Panfilova M, Mikhaylova E (2021) Anthocyanin biosynthesis genes as model genes for genome editing in plants. Int J Mol Sci. https://doi.org/10.3390/ijms22168752

    Article  PubMed  PubMed Central  Google Scholar 

  • Kumar R, Vashisth D, Misra A, Akhtar MQ, Jalil SU, Shanker K, Gupta MM, Rout PK, Gupta AK, Shasany AK (2016) RNAi down-regulation of cinnamate-4-hydroxylase increases artemisinin biosynthesis in Artemisia annua. Sci Rep 6:26458. https://doi.org/10.1038/srep26458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lai HC, Singh NP, Sasaki T (2013) Development of artemisinin compounds for cancer treatment. Invest New Drugs 31(1):230–246

    Article  CAS  PubMed  Google Scholar 

  • Li J, Casteels T, Frogne T, Ingvorsen C, Honore C, Courtney M, Huber KV, Schmitner N, Kimmel RA, Romanov RA (2017) Artemisinins target GABAA receptor signaling and impair α cell identity. Cell 168(1–2):86-100.e115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, He X, La Hovary C, Zhu Y, Dong Y, Liu S, Xing H, Liu Y, Jie Y, Ma D, Yuzuak S, Xie D-Y (2022) A de novo regulation design shows an effectiveness in altering plant secondary metabolism. J Adv Res 37:43–60. https://doi.org/10.1016/j.jare.2021.06.017

    Article  CAS  PubMed  Google Scholar 

  • Liao BS, Shen XF, Xiang L, Guo S, Chen SY, Meng Y, Liang Y, Ding DD, Bai JQ, Zhang D, Czechowski T, Li Y, Yao H, Ma TY, Howard C, Sun C, Liu HT, Liu JS, Pei J, Gao JH, Wang JG, Qiu XH, Huang ZH, Li HY, Yuan L, Wei JH, Graham I, Xu J, Zhang BL, Chen SL (2022) Allele-aware chromosome-level genome assembly of Artemisia annua reveals the correlation between ADS expansion and artemisinin yield. Mol Plant 15(8):1310–1328. https://doi.org/10.1016/j.molp.2022.05.013

    Article  CAS  PubMed  Google Scholar 

  • Liu S, Liu L, Tang Y, Xiong S, Long J, Liu Z, Tian N (2017) Comparative transcriptomic analysis of key genes involved in flavonoid biosynthetic pathway and identification of a flavonol synthase from Artemisia annua L. Plant Biol 19(4):618–629. https://doi.org/10.1111/plb.12562

    Article  CAS  PubMed  Google Scholar 

  • Ma D-M, Wang Z, Wang L, Alejos-Gonzales F, Sun M-A, Xie D-Y (2015) A genome-wide scenario of terpene pathways in self-pollinated Artemisia annua. Mol Plant 8(11):1580–1598. https://doi.org/10.1016/j.molp.2015.07.004

    Article  CAS  PubMed  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(2):173–180

    Article  CAS  PubMed  Google Scholar 

  • Merzlyak MN, Chivkunova OB, Solovchenko AE, Naqvi KR (2008) Light absorption by anthocyanins in juvenile, stressed, and senescing leaves. J Exp Bot 59(14):3903–3911. https://doi.org/10.1093/jxb/ern230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mohammad SS, Santos RO, Barbosa MI, Barbosa JL (2021) Anthocyanins: chemical properties and health benefits: a review. Curr Nutr Food Sci 17(7):662–672. https://doi.org/10.2174/1573401317999210101150652

    Article  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(7446):528–532. https://doi.org/10.1038/nature12051

    Article  CAS  PubMed  Google Scholar 

  • Pandey N, Pandey-Rai S (2014a) Modulations of physiological responses and possible involvement of defense-related secondary metabolites in acclimation of Artemisia annua L. against short-term UV-B radiation. Planta 240(3):611–627. https://doi.org/10.1007/s00425-014-2114-2

    Article  CAS  PubMed  Google Scholar 

  • Pandey N, Pandey-Rai S (2014b) Short term UV-B radiation-mediated transcriptional responses and altered secondary metabolism of in vitro propagated plantlets of Artemisia annua L. Plant Cell Tissue Organ Cult 116(3):371–385. https://doi.org/10.1007/s11240-013-0413-0

    Article  CAS  Google Scholar 

  • Pandey N, Goswami N, Tripathi D, Rai KK, Rai SK, Singh S, Pandey-Rai S (2019) Epigenetic control of UV-B-induced flavonoid accumulation in Artemisia annua L. Planta 249(2):497–514. https://doi.org/10.1007/s00425-018-3022-7

    Article  CAS  PubMed  Google Scholar 

  • Pang QQ, Yu WB, Sadeghnezhad E, Chen XQ, Hong PJ, Pervaiz T, Ren YH, Zhang YP, Dong TY, Jia HF, Fang JG (2023) Omic analysis of anthocyanin synthesis in wine grape leaves under low-temperature. Sci Hortic. https://doi.org/10.1016/j.scienta.2022.111483

    Article  Google Scholar 

  • Qu Y, Bai X, Zhu YJ, Qi R, Tian G, Wang Y, Li YH, Zhang KM (2018) Reactive oxygen species acts as an important inducer in low-temperature-induced anthocyanin biosynthesis in Begonia semperflorens. J Am Soc Hortic Sci 143(6):486. https://doi.org/10.21273/jashs04488-18

    Article  CAS  Google Scholar 

  • Ro D-K, Paradise EM, Ouellet M, Fisher KJ, Newman KL, Ndungu JM, Ho KA, Eachus RA, Ham TS, Kirby J, Chang MCY, Withers ST, Shiba Y, Sarpong R, Keasling JD (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440(7086):940–943

    Article  CAS  PubMed  Google Scholar 

  • Rowan DD, Cao M, Kui L-W, Cooney JM, Jensen DJ, Austin PT, Hunt MB, Norling C, Hellens RP, Schaffer RJ, Allan AC (2009) Environmental regulation of leaf colour in red 35S:PAP1 Arabidopsis thaliana. New Phytol 182(1):102–115

    Article  CAS  PubMed  Google Scholar 

  • Schramek N, Wang H, Römisch-Margl W, Keil B, Radykewicz T, Winzenhörlein B, Beerhues L, Bacher A, Rohdich F, Gershenzon J, Liu B, Eisenreich W (2010) Artemisinin biosynthesis in growing plants of Artemisia annua. A 13CO2 study. Phytochemistry 71(2):179–187. https://doi.org/10.1016/j.phytochem.2009.10.015

    Article  CAS  PubMed  Google Scholar 

  • Shi M-Z, Xie D-Y (2010) Features of anthocyanin biosynthesis in pap1-D and wild-type Arabidopsis thaliana plants grown in different light intensity and culture media conditions. Planta 231:1385–1400

    Article  CAS  PubMed  Google Scholar 

  • Shi MZ, Xie DY (2011) Engineering of red cells of Arabidopsis thaliana and comparative genome-wide gene expression analysis of red cells versus wild-type cells. Planta 233(4):787–805. https://doi.org/10.1007/s00425-010-1335-2

    Article  CAS  PubMed  Google Scholar 

  • Shi M-Z, Xie D-Y (2014) Biosynthesis and metabolic engineering of anthocyanins in Arabidopsis thaliana. Recent Pat Biotechnol 8(1):47–60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shretta R, Yadav P (2012) Stabilizing supply of artemisinin and artemisinin-based combination therapy in an era of wide-spread scale-up. Malar J 11(1):399

    Article  PubMed  PubMed Central  Google Scholar 

  • Srivastava S, Sangwan RS (2012) Analysis of Artemisia annua transcriptome for BAHD alcohol acyltransferase genes: identification and diversity of expression in leaf, stem and root. J Plant Biochem Biotechnol 21(1):S108–S118. https://doi.org/10.1007/s13562-012-0141-2

    Article  CAS  Google Scholar 

  • Sy LK, Brown GD (2002a) The mechanism of the spontaneous autoxidation of dihydroartemisinic acid. Tetrahedron 58(5):897–908. https://doi.org/10.1016/s0040-4020(01)01193-0

    Article  CAS  Google Scholar 

  • Sy LK, Brown GD (2002b) The role of the 12-carboxyllic acid group in the spontaneous autoxidation of dihydroartemisinic acid. Tetrahedron 58(5):909–923. https://doi.org/10.1016/s0040-4020(01)01192-9

    Article  CAS  Google Scholar 

  • 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(5):1411–1416

    Article  CAS  PubMed  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(6):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(12):2129–2136. https://doi.org/10.1007/s00299-007-0420-x

    Article  CAS  PubMed  Google Scholar 

  • Wallaart TE, van Uden W, Lubberink HG, Woerdenbag HJ, Pras N, Quax WJ (1999) Isolation and identification of dihydroartemisinic acid from Artemisia annua and its possible role in the biosynthesis of artemisinin. J Nat Prod 62(3):430–433

    Article  CAS  PubMed  Google Scholar 

  • Wallaart TE, Pras N, Beekman AC, Quax WJ (2000) Seasonal variation of artemisinin and its biosynthetic precursors in plants of Artemisia annua of different geographical origin: proof for the existence of chemotypes. Planta Med 66(1):57–62

    Article  CAS  PubMed  Google Scholar 

  • WHO (2010) Good procurement practices for artemisinin-based antimalarial medicines. WHO Global Malaria Programme

  • WHO (2018) World Malaria Report 2018. World Malaria Report

  • WHO (2021) World malaria report 2021. World Health Orgnization

  • Xiao L, Tan HX, Zhang L (2016) Artemisia annua glandular secretory trichomes: the biofactory of antimalarial agent artemisinin. Sci Bull 61(1):26–36. https://doi.org/10.1007/s11434-015-0980-z

    Article  CAS  Google Scholar 

  • Xie DY (2016) Artemisia annua, artemisinin, and the Nobel Prize: beauty of natural products and educational significance. Sci Bull 61(1):42–44. https://doi.org/10.1007/s11434-015-0989-3

    Article  Google Scholar 

  • Xie D-Y, Dixon RA (2005) Proanthocyanidin biosynthesis—still more questions than answers? Phytochemistry 66(18):2127–2144

    Article  CAS  PubMed  Google Scholar 

  • Xie DY, Hong Y (2001) Regeneration of Acacia mangium through somatic embryogenesis. Plant Cell Rep 20(1):34

    Article  CAS  PubMed  Google Scholar 

  • Xie D-Y, Sharma SB, Wright E, Wang Z-Y, Dixon RA (2006) Metabolic engineering of proanthocyanidins through co-expression of anthocyanidin reductase and the PAP1 MYB transcription factor. Plant J 45(6):895–907. https://doi.org/10.1111/j.1365-313X.2006.02655.x

    Article  CAS  PubMed  Google Scholar 

  • Xie D-Y, Ma D-M, Judd R, Jones AL (2016) Artemisinin biosynthesis in Artemisia annua and metabolic engineering: questions, challenges, and perspectives. Phytochem Rev 15(6):1093–1114. https://doi.org/10.1007/s11101-016-9480-2

    Article  CAS  Google Scholar 

  • Xiong S, Tian N, Long J, Chen Y, Qin Y, Feng J, Xiao W, Liu S (2016) Molecular cloning and characterization of a flavanone 3-hydroxylase gene from Artemisia annua L. Plant Physiol Biochem 105:29–36

    Article  CAS  PubMed  Google Scholar 

  • 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(7):734–742. https://doi.org/10.1055/s-0029-1240620

    Article  CAS  PubMed  Google Scholar 

  • Yuzuak S, Xie D-Y (2022) Anthocyanins from muscadine (Vitis rotundifolia) grape fruit. Curr Plant Biol 30:100243. https://doi.org/10.1016/j.cpb.2022.100243

    Article  CAS  Google Scholar 

  • Yuzuak S, Ballington J, Xie D-Y (2018) HPLC-qTOF-MS/MS-based profiling of flavan-3-ols and dimeric proanthocyanidins in berries of two muscadine grape Hybrids FLH 13–11 and FLH 17–66. Metabolites 8(4):57. https://doi.org/10.3390/metabo8040057

    Article  CAS  PubMed  PubMed Central  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 Δ-11(13) reductase and its role in glandular trichome-dependent biosynthesis of artemisinin in Artemisia annua. J Biol Chem 283:21501–21508. https://doi.org/10.1074/jbc.M803090200

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Butelli E, Martin C (2014) Engineering anthocyanin biosynthesis in plants. Curr Opin Plant Biol 19:81–90. https://doi.org/10.1016/j.pbi.2014.05.011

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Fu X, Lv Z, Lu X, Shen Q, Zhang L, Zhu M, Wang G, Sun X, Liao Z (2015) A basic leucine zipper transcription factor, AabZIP1, connects abscisic acid signaling with artemisinin biosynthesis in Artemisia annua. Mol Plant 8(1):163–175

    Article  CAS  PubMed  Google Scholar 

  • Zhang N, Sun QQ, Li HF, Li XS, Cao YY, Zhang HJ, Li ST, Zhang L, Qi Y, Ren SX, Zhao B, Guo YD (2016) Melatonin improved anthocyanin accumulation by regulating gene expressions and resulted in high reactive oxygen species scavenging capacity in cabbage. Front Plant Sci. https://doi.org/10.3389/fpls.2016.00197

    Article  PubMed  PubMed Central  Google Scholar 

  • Zvi MMB, Shklarman E, Masci T, Kalev H, Debener T, Shafir S, Ovadis M, Vainstein A (2012) PAP1 transcription factor enhances production of phenylpropanoid and terpenoid scent compounds in rose flowers. New Phytol 195(2):335–345

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank College of Agriculture and Life Sciences Dean’s Graduate Research Assistantship and US Department of Education GAANN Biotechnology Fellowship, NC State University for supporting Rika Judd’s PhD study. We thank China Scholar Council for supporting Yilun Dong’s PhD Exchange Scholarship.

Author information

Author notes

  1. Rika Judd and Yilun Dong have equally contributed to this work.

Authors and Affiliations

  1. Department of Plant and Microbial Biology, North Carolina State University, Raleigh, NC, USA

    Rika Judd, Yilun Dong, Yue Zhu, Mingzhuo Li & De-Yu Xie

  2. Rice Research Institute, Sichuan Agricultural University, Chengdu, China

    Yilun Dong

  3. Department of Chemistry, North Carolina State University, Raleigh, NC, USA

    Xiaoyan Sun

Authors
  1. Rika Judd
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yilun Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaoyan Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yue Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mingzhuo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. De-Yu Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to De-Yu Xie.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

Additional information

Communicated by Anastasios Melis.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 1817 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Judd, R., Dong, Y., Sun, X. et al. Metabolic engineering of the anthocyanin biosynthetic pathway in Artemisia annua and relation to the expression of the artemisinin biosynthetic pathway. Planta 257, 63 (2023). https://doi.org/10.1007/s00425-023-04091-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00425-023-04091-6

Keywords

Search

Navigation