Skip to main content
SpringerLink
Log in

Singlet oxygen as a signaling transducer for modulating artemisinin biosynthetic genes in Artemisia annua

  • Published:
Biologia Plantarum

Abstract

Although crosstalk between cytosolic and plastidic terpenoid pathways has been validated in many plant species, we report here for the first time a striking elevation of the nucleus-encoded artemisinin biosynthesis relevant DBR2 mRNA following the incubation of plants with fosmidomycin (FM). FM decreased singlet oxygen (1O2) scavengers such as β-carotene and α-tocopherol and subsequently invoked 1O2 burst. The treatment of plants with fluridone (FD) neither decreased α-tocopherol content nor triggered 1O2 emission. In conclusion, FM can up-regulate 1O2-sensitive nuclear genes responsible for artemisinin biogenesis by mitigating the accumulation of plastidic scavenging terpenoids, thereby eliciting 1O2 generation and initiating 1O2 retrograde signaling.

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

Similar content being viewed by others

Abbreviations

ADS:

amorpha-4,11-dienesynthase

CPR:

cytochrome P450 reductase

CYP71AV1:

cytochrome P450 monooxygenase

DBR2:

Δ11(13)-double-bond reductase 2

DHAA:

dihydroartemisinic acid

DXP:

1-deoxy-O-xylulose-5-phosphate

DXR:

DXP reductoisomerase

DXS:

DXP synthase

FD:

fluridone

FM:

fosmidomycin

FPP:

farnesyl pyrophosphate

MVA:

mevalonic acid

References

  • Bartels, P.G., Watson, C.W.: Inhibition of carotenoid synthesis by fluridone and norflurazon. — Weed Sci. 26: 198–203, 1978.

    CAS  Google Scholar 

  • Benderliev, K.M., Ivanova, N.I., Pilarski, P.S.: Singlet oxygen and other reactive oxygen species are involved in regulation of release of iron-binding chelators from Scenedesmus cells. — Biol. Plant. 47: 523–526, 2003.

    Article  CAS  Google Scholar 

  • Bertea, C.M., Freije, J.R., Van der Woude, H., Verstappen, F.W., Perk, L., Marquez, V., De Kraker, J.W., Posthumus, M.A., Jansen, B.J., De Groot, A., Franssen, M.C., Bouwmeester, H.J.: Identification of intermediates and enzymes involved in the early steps of artemisinin biosynthesis in Artemisia annua. — Planta med. 71: 40–47, 2005.

    Article  PubMed  CAS  Google Scholar 

  • Bertea, C.M., Voster, A., Verstappen, F.W., Maffei, M., Beekwilder, J., Bouwmeester, H.J.: Isoprenoid biosynthesis in Artemisia annua: cloning and heterologous expression of a germacrene A synthase from a glandular trichome cDNA library. — Arch. Biochem. Biophys. 448: 3–12, 2006.

    Article  PubMed  CAS  Google Scholar 

  • Chappell, J.: The genetics and molecular genetics of terpene and sterol origami. — Curr. Opin. Plant Biol. 5: 151–157, 2002.

    Article  PubMed  CAS  Google Scholar 

  • Covello, P. S.: Making artemisinin. — Phytochemistry 69: 2881–2885, 2008.

    Article  PubMed  CAS  Google Scholar 

  • Covello, P.S., Teoh, K.H., Polichuk, D.R., Reed, D.W., Nowak, G.: Functional genomics and the biosynthesis of artemisinin. — Phytochemistry 68: 1864–1871, 2007.

    Article  PubMed  CAS  Google Scholar 

  • Feng, L.L., Yang, R.Y., Yang, X.Q., Zeng, X.M., Lu, W.J., Zeng, Q.P.: Synergistic re-channeling of mevalonate pathway for artemisinin overproduction in transgenic Artemisia annua. — Plant Sci. 177: 57–67, 2009.

    Article  CAS  Google Scholar 

  • Guo, X.X., Yang, X.Q., Yang, R.Y., Zeng, Q.P.: Salicylic acid and methyl jasmonate but not Rose Bengal up-regulate artemisinin biosynthetic genes through invoking burst of endogenous singlet oxygen. — Plant Sci. 178: 390–397, 2010.

    Article  CAS  Google Scholar 

  • Hirayama, O., Nakamura, K., Hamada, S., Kobayashi, Y.: Singlet oxygen quenching ability of naturally occurring carotenoids. — Lipids 29: 149–150, 1994.

    Article  PubMed  CAS  Google Scholar 

  • Kim, S.H., Chang, Y.J., Kim, S.U.: 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, 2008.

    Article  PubMed  CAS  Google Scholar 

  • Laloi, C., Przybyla, D., Apel, K.: A genetic approach towards elucidating the biological activity of different reactive oxygen species in Arabidopsis thaliana.— J. exp. Bot. 57: 1719–1724, 2006.

    Article  PubMed  CAS  Google Scholar 

  • Laloi, C., Stachowiak, M., Pers-Kamczyc, E., Warzych, I.M., Apel, K.: Cross-talk between singlet oxygen- and hydrogen peroxide-dependent signalling of stress responses in Arabidopsis thaliana. — Proc. nat. Acad. Sci. USA 104: 672–677, 2007.

    Article  PubMed  CAS  Google Scholar 

  • Laule, O., Furholz, A., Chang, H.S., Zhu, T., Wang, X., Heifetz, P.B., Gruissem, W., Lange, M.: Crosstalk between cytosolic and plastidial pathways of isoprenoid biosynthesis in Arabidopsis thaliana. — Proc. nat. Acad. Sci. USA 100: 6866–6871, 2003.

    Article  PubMed  CAS  Google Scholar 

  • Lee, K.P., Kim, C., Landgraf, F., Apel, K.: EXECUTER1- and EXECUTER2-dependent transfer of stress-related signals from the plastid to the nucleus of Arabidopsis thaliana. —Proc. nat. Acad. Sci. USA 104: 10270–10275, 2007.

    Article  PubMed  CAS  Google Scholar 

  • Maeda, H., Sakuragi, Y., Bryant, D.A., Della Penna, D.: Tocopherols protect Synechocystis sp. strain PCC 6803 from lipid peroxidation. — Plant Physiol. 138: 1422–1435, 2005.

    Article  PubMed  CAS  Google Scholar 

  • Ro, D.K., Paradise, E.M., Ouelle, t M., Fisher, K.J., Newman, K.L., Ndungu, J.M., Ho, K.A., Eachus, R.A., Ham, T.S., Kirby, J., Chang, M.C., Withers, S.T., Shiba, Y., Sarpong, R., Keasling, J.D.: Production of the antimalarial drug precursor artemisinic acid in engineered yeast. — Nature 440: 940–943, 2006.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Concepcion, M., Fores, O., Martinez-Garcia, J.F., Gonzalez, V., Phillips, M.A., Ferrer, A., Boronat, A.: Distinct light-mediated pathways regulate the biosynthesis and exchange of isoprenoid precursors during Arabidopsis seedling development. — Plant Cell 16: 144–156, 2004.

    Article  PubMed  CAS  Google Scholar 

  • Sy, L.K., Brown, G.D.: The mechanism of the spontaneous autoxidation of dihydroartemisinic acid. — Tetrahedron 58: 897–908, 2002.

    Article  CAS  Google Scholar 

  • Teoh, K.H., Polichuk, D.R., Reed, D.W., Nowak, G., Covello, P. S.: 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, 2006.

    Article  PubMed  CAS  Google Scholar 

  • Towler, M.J., Weathers, P.J.: Evidence of artemisinin production from IPP stemming from both the mevalonate and the nonmevalonate pathways. — Plant Cell Rep. 26: 2129–2136, 2007.

    Article  PubMed  CAS  Google Scholar 

  • Triantaphylides, C., Havaux, M.: Singlet oxygen in plants: production, detoxification and signaling. — Trends Plant Sci. 14: 219–228, 2009.

    Article  PubMed  CAS  Google Scholar 

  • Wallaart, T.E., Van Uden, W., Lubberink, H.G.M., Woerdenbag, H.J., Pras, N., Quax, W.J.: Isolation and identification of dihydroartemisinic acid from Artemisia annua and its possible role in the biosynthesis of artemisinin. — J. natur. Prod. 62: 430–433, 1999.

    Article  CAS  Google Scholar 

  • Wu, S., Schalk, M., Clark, A., Miles, R.B., Coates, R., Chappell, J.: Redirection of cytosolic or plastidic isoprenoid precursors elevates terpene production in plants. — Nat. Biotechnol. 24: 1441–1447, 2006.

    Article  PubMed  CAS  Google Scholar 

  • Xu, X., Hu, X., Neill, S.J., Fang, J., Cai, W.: Fungal elicitor induces singlet oxygen generation, ethylene release and saponin synthesis in cultured cells of Panax ginseng C.A. Meyer. — Plant Cell Physiol. 46: 947–954, 2005.

    Article  PubMed  CAS  Google Scholar 

  • Yang, R.Y., Feng, L.L., Yang, X.Q., Yin, L.L., Xu, X.L., Zeng, Q.P.: Quantitative transcript profiling reveals downregulation of a steroid pathway relevant gene and overexpression of artemisinin biogenetic genes in transgenic Artemisia annua plants. — Planta med. 74: 1510–1516, 2008.

    Article  PubMed  CAS  Google Scholar 

  • Yang, R.Y., Zeng, X.M., Lu, Y.Y., Lu, W.J., Feng, L.L., Yang, X.Q., Zeng, Q.P.: Senescent leaves of Artemisia annua are one of the most active organs for overexpression of artemisinin biosynthesis responsible genes upon burst of singlet oxygen. — Planta med. 76: 734–742, 2010.

    Article  PubMed  CAS  Google Scholar 

  • Yin, L.L., Zhao, C., Huang, Y., Yang, R.Y.: Abiotic stressinduced expression of artemisinin biosynthesis genes in Artemisia annua L. — Chin. appl. environ. Biol. 14: 1–5, 2008.

    CAS  Google Scholar 

  • Zeng, Q.P., Qiu, F., Yuan, L.: Production of artemisinin by genetically modified microbes. — Biotechnol. Lett. 30: 581–592, 2008a.

    Article  PubMed  CAS  Google Scholar 

  • Zeng, Q.P., Yang, R.Y., Feng, L.L., Yang, X.Q.: Genetic and environmental regulation and artificial metabolic manipulation for artemisinin biosynthesis. — In: Richter, F.W. (ed.): Biotechnology: Research, Technology and Applications. Pp. 159–210. Nova Science Publishers, New York 2008b.

    Google Scholar 

  • Zeng, Q.P., Zeng, X.M., Feng, L.L., Yin, L.L., Yang, X.Q., Yang, R.Y.: Quantification of three key enzymes involved in artemisinin biosynthesis in Artemisia annua by polyclonal antisera-based ELISA. — Plant mol. Biol. Rep. 27: 50–57, 2009.

    Article  CAS  Google Scholar 

  • Zeng, Q.P., Zhao, C., Yin, L.L., Yang, R.Y., Zeng, X.M., Huang, Y., Feng, L.L., Yang, X.Q.: Cloning of artemisinin biosynthetic cDNAs and novel ESTs and quantification of low temperature-induced gene overexpression. — Sci. China Ser. C 51: 232–244, 2008c.

    Article  CAS  Google Scholar 

  • Zhang, Y.S., Teoh, K.H., Reed, D.W., Maes, L., Goossens, A., Olson, D.J.H., Ross, A.R.S., Covello, P.S.: 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, 2008.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Li-Xiang Zeng, Xiao-Xia Guo and Ping-Zu Zhang for their helpful assistance. This work is financially supported by the National Natural Science Foundation of China (NSFC) (No. 30271591) and Guangdong Provincial Scientific Development Project of China (No. 2007B031404008).

Author information

Authors and Affiliations

  1. Laboratory of Biotechnology, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, 510405, Guangzhou, P.R. China

    Q. -P. Zeng, X. -M. Zeng, R. -Y. Yang & X. -Q. Yang

Authors
  1. Q. -P. Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. X. -M. Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. -Y. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X. -Q. Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Q. -P. Zeng.

Additional information

Authors contributing equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zeng, Q.P., Zeng, X.M., Yang, R.Y. et al. Singlet oxygen as a signaling transducer for modulating artemisinin biosynthetic genes in Artemisia annua . Biol Plant 55, 669–674 (2011). https://doi.org/10.1007/s10535-011-0166-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10535-011-0166-8

Additional key words

Search

Navigation