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Abscisic acid (ABA) treatment increases artemisinin content in Artemisia annua by enhancing the expression of genes in artemisinin biosynthetic pathway

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Abstract

Artemisinin, a sesquiterpene lactone endoperoxide derived from Artemisia annua L., is the most effective antimalarial drug. In an effort to increase the artemisinin production, abscisic acid (ABA) with different concentrations (1, 10 and 100 µM) was tested by treating A. annua plants. As a result, the artemisinin content in ABA-treated plants was significantly increased. Especially, artemisinin content in plants treated by 10 µM ABA was 65% higher than that in the control plants, up to an average of 1.84% dry weight. Gene expression analysis showed that in both the ABA-treated plants and cell suspension cultures, HMGR, FPS, CYP71AV1 and CPR, the important genes in the artemisinin biosynthetic pathway, were significantly induced. While only a slight increase of ADS expression was observed in ABA-treated plants, no expression of ADS was detected in cell suspension cultures. This study suggests that there is probably a crosstalk between the ABA signaling pathway and artemisinin biosynthetic pathway and that CYP71AV1, which was induced most significantly, may play a key regulatory role in the artemisinin biosynthetic pathway.

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Abbreviations

ABA:

abscisic acid

ADS :

amorpha-4,11-diene synthase gene

CPR :

cytochrome P450 reductase gene

CYP71AV1 :

amorpha-4,11-diene C-12 oxidase gene

FPS :

farnesyl diphosphate synthase gene

HMGR :

3-hydroxy-3-methylglutaryl coenzyme A reductase gene

HPLC-ELSD:

high performance liquid chromatography coupled with evaporative light scattering detection

References

  • Abdin M.Z., Israr M., Rehman R.U. & Jain S.K. 2003. Artemisinin, a novel antimalarial drug: biochemical and molecular approaches for enhanced production. Planta Med. 69: 289–299.

    Article  PubMed  CAS  Google Scholar 

  • Baldi A. & Dixit V.K. 2008. Yield enhancement strategies for artemisinin production by suspension cultures of Artemisia annua. Bioresour. Technol. 99: 4609–4614.

    Article  PubMed  CAS  Google Scholar 

  • Barrero J.M., Rodriguez P.L., Quesada V., Piqueras P., Ponce M.R. & Micol J.L. 2006. Both abscisic acid (ABA)-dependent and ABA-independent pathways govern the induction of NCED3, AAO3 and ABA1 in response to salt stress. Plant Cell Environ. 29: 2000–2008.

    Article  PubMed  CAS  Google Scholar 

  • Chappell J., VonLanken C. & Vogell U. 1991. Elicitor-inducible 3-hydroxy-3-methylglutaryl coenzyme A reductase activity is required for sesquiterpene accumulation in tobacco cell suspension cultures. Plant Physiol. 97: 693–698.

    Article  PubMed  CAS  Google Scholar 

  • Chappell J., Wolf F., Proulx J., Cuellar R. & Saunders C. 1995. Is the reaction catalyzed by 3-hydroxy-3-methylglutaryl coenzyme A reductase a rate-limiting step for isoprenoid biosynthesis in plants? Plant Physiol. 109: 1337–1343.

    PubMed  CAS  Google Scholar 

  • Chen D.H., Ye H.C. & Li G.F. 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 

  • Fulzele D.P., Heble M.R. & Rao P.S. 1995. Production of terpenoid from Artemisia annua L. plantlet cultures in bioreactor. J. Biotechnol. 40: 139–143.

    Article  CAS  Google Scholar 

  • Guo C., Liu C.Z., Ye H.C. & Li G.F. 2004. Effect of temperature on growth and artemisinin biosynthesis in hairy root cultures of Artemisia annua. Acta Botanica Boreali — Occidentalia Sinica 24: 1828–1831.

    CAS  Google Scholar 

  • Kim S.H., Chang Y.J. & Kim S.U. 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 

  • Liersch R., Soicke H., Stehr C. & Tullner H.U. 1986 Formation of artemisinin in Artemisia annua during one vegetation period. Planta Med. 52: 387–390.

    Article  PubMed  CAS  Google Scholar 

  • Liu C.Z., Guo C., Wang Y.C. & Ouyang F. 2002. Effect of light irradiation on hairy root growth and artemisinin biosynthesis of Artemisia annua L. Process Biochem. 38: 581–585.

    Article  CAS  Google Scholar 

  • Liu C.Z., Zhao Y. & Wang Y.C. 2006 Artemisinin: current state and perspectives for biotechnological production of an antimalarial drug. Appl. Microbiol. Biotechnol. 71: 11–20.

    Article  Google Scholar 

  • Mercke P., Bengtsson M., Bouwmeester H.J., Posthumus M.A. & Brodelius P.E. 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 

  • Nair M.S., Acton N., Klayman D.L., Kendrick K., Basile D.V. & Mante S. 1986. Production of artemisinin in tissue cultures of Artemisia annua. J. Nat. Prod. 49: 504–507.

    Article  PubMed  CAS  Google Scholar 

  • Putalun W., Luealon W., De-Eknamkul W., Tanaka H. & Shoyama Y. 2007. Improvement of artemisinin production by chitosan in hairy root cultures of Artemisia annua L. Biotechnol. Lett. 29: 1143–1146.

    Article  PubMed  CAS  Google Scholar 

  • Qian Z.H., Gong K., Zhang L., Lv J.B., Jing F.Y., Wang Y.Y., Guan S.B., Wang G.F. & Tang K.X. 2007. A simple and efficient procedure to enhance artemisinin content in Artemisia annua L. by seeding to salinity stress. Afric. J. Biotechnol. 6: 1410–1413.

    CAS  Google Scholar 

  • Qureshi M.I., Israr M., Abdin M.Z. & Iqbal M. 2005. Responses of Artemisia annua L. to lead and salt-induced oxidative stress. Environ. Exp. Bot. 53: 185–193.

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Smet I.D., Zhang H., Inze D. & Beeckman T. 2006. A novel role for abscisic acid emerges from underground. Trends Plant Sci. 11: 434–439.

    Article  PubMed  Google Scholar 

  • Smith J.I., Smart N.J., Kurz W.G. & Misawa M. 1987. Stimulation of indole alkaloid production in cell suspension cultures of Catharanthus roseus by abscisic acid. Planta Med. 53: 470–474.

    Article  PubMed  CAS  Google Scholar 

  • Smith T.C., Weathers P.J. & Cheetham R.C. 1997. Effect of gibberellic acid on hair root cultures of Artemisia annua growth and artemisinin production. In Vitro Cell. Dev. Biol. Plant 33: 75–79.

    Article  CAS  Google Scholar 

  • Tawfiq N.K., Anderson L.A., Roberts M.F., Phillipson J.D., Bray D.H. & Warhurst D.C. 1989. Antiplasmodial activity of Artemisia annua plant cell cultures. Plant Cell Rep. 8: 425–428.

    Article  Google Scholar 

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

  • Verslues P.E. & Zhu J.K. 2005. Before and beyond ABA: upstream sensing and internal signals that determine ABA accumulation and response under abiotic stress. Biochem. Soc. Trans. 33: 375–379.

    Article  PubMed  CAS  Google Scholar 

  • Wallaart T.E., Bouwmeester H.J., Hille J., Poppinga L. & Maijers N.C.A. 2001. Amorpha-4,11-diene systhase: cloning and functional expression of a key enzyme in the biosynthetic pathway of the novel antimalarial drug artemisnin. Planta 212: 460–465.

    Article  PubMed  CAS  Google Scholar 

  • Wang Y.C., Zhang H.X., Zhao B. & Yuan X.F. 2001. Improved growth of Artemisia annua L. hairy roots and artemisinin production under red light conditions. Biotechnol. Lett. 23: 1971–1973.

    Article  CAS  Google Scholar 

  • Weathers P.J., Bunk G. & Mccoy M.C. 2005. The effect of phytohormones on growth and artemisinin production in Artemisia annua hairy roots. In Vitro Cell. Dev. Biol.Plant 41: 47–53.

    Article  CAS  Google Scholar 

  • Whipkey A., Simon J.E., Charles D.J. & Janick J. 1992. In vitro production of artemisinin from Artemisia annua L. Phytother. Res. 1: 15–25.

    Google Scholar 

  • Zhang Y.S., Ye H.C., Liu B.Y., Wang H & Li G.F. 2005. Exogenous GA and flowering induce the conversion of artemisinic acid to artemisinin in Artemisia annua plants. Russian J. Plant Physiol. 52: 58–62.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Plant Biotechnology Research Center, Fudan-SJTU-Nottingham Plant Biotechnology R&D Center, School of Agriculture and Biology, School of Life Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China

    Fuyuan Jing, Ling Zhang, Meiya Li, Yueli Tang, Yuliang Wang, Yueyue Wang, Quan Wang, Qifang Pan, Guofeng Wang & Kexuan Tang

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  1. Fuyuan Jing
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  2. Ling Zhang
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  3. Meiya Li
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  4. Yueli Tang
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  5. Yuliang Wang
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  6. Yueyue Wang
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  7. Quan Wang
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  8. Qifang Pan
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  9. Guofeng Wang
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  10. Kexuan Tang
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Correspondence to Kexuan Tang.

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Jing, F., Zhang, L., Li, M. et al. Abscisic acid (ABA) treatment increases artemisinin content in Artemisia annua by enhancing the expression of genes in artemisinin biosynthetic pathway. Biologia 64, 319–323 (2009). https://doi.org/10.2478/s11756-009-0040-8

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  • DOI: https://doi.org/10.2478/s11756-009-0040-8

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