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Genetically modified rice produces ginsenoside aglycone (protopanaxadiol)

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Abstract

Main conclusion

Protopanaxadiol is dammarane-type tetracyclic triterpene sapogenin found in ginseng and has a high medicinal values. We successfully constructed transgenic rice producing protopanaxadiol by introducing the ginseng PgDDS and CYP716A47 genes in this crop plant.

Abstract

Protopanaxadiol (PPD), an aglycone of ginsenosides, possesses pleiotropic anticarcinogenesis activities in many cancers. Here, we constructed transgenic rice overexpressing the Panax ginseng dammarenediol-II synthase gene (PgDDS) and protopanaxadiol synthase gene (CYP716A47) driven by a rice endosperm-specific α-globulin promoter. Among more than 50 independent lines, five transgenic lines were selected. The introduction of the genes in the T1 generation of the transgenic lines was confirmed by genomic PCR. The expression of the introduced genes in T2 seeds was confirmed by qPCR. Methanol extracts of transgenic rice grains were analyzed by LC/MS to detect the production of PPD and dammarenediol-II (DD). The production of both PPD and DD was identified not only by comparing the retention times but also mass fraction patterns of authentic PPD and DD standards. The mean concentrations of PPD and DD in rice grains were 16.4 and 4.5 µg/g dry weight, respectively. The invention of genetically engineered rice grains producing PPD and DD can be applied to rice breeding to reinforce new medicinal values.

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References

  • Akihisa T, Tokuda H, Ukiya M, Suzuki T, Enjo F, Koike K, Nikaido T, Nishino H (2004) 3-epicabraleahydroxylactone and other triterpenoids from Camellia oil and their inhibitory effects on Epstein–Barr virus activation. Chem Pharm Bull 52:153–156

    Article  CAS  PubMed  Google Scholar 

  • Baek SH, Shin WC, Ryu HS, Lee DW, Moon E, Seo CS, Hwang E, Lee HS, Ahn MH, Jeon Y, Kang HJ, Lee SW, Kim SY, D’Souza R, Kim HJ, Hong ST, Jeon JS (2014) Creation of resveratrol-enriched rice for the treatment of metabolic syndrome and related diseases. PLoS One 8:e57930

    Article  CAS  Google Scholar 

  • Chen XJ, Zhang XJ, Shui YM, Wan JB, Gao JL (2016) Anticancer activities of protopanaxadiol- and protopanaxatriol-type ginsenosides and their metabolites. Evid Based Complement Altern Med 2016:5738694

    Google Scholar 

  • Dang H, Chen Y, Liu X, Wang Q, Wang L, Jia W, Wang Y (2009) Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression. Prog Neuropsychopharmacol Biol Psychiatry 33:1417–1424

    Article  CAS  PubMed  Google Scholar 

  • Faizal A, Geelen D (2013) Saponins and their role in biological processes in plants. Phytochem Rev 12:877–893

    Article  CAS  Google Scholar 

  • Han JY, Kwon YS, Yang DC, Jung YR, Choi YE (2006) Expression and RNA interference-induced silencing of the dammarenediol synthase gene in Panax ginseng. Plant Cell Physiol 47:1653–1662

    Article  CAS  PubMed  Google Scholar 

  • Han JY, Kim HJ, Kwon YS, Choi YE (2011) The cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol 52:2062–2073

    Article  CAS  PubMed  Google Scholar 

  • Han JY, Hwang HS, Choi SW, Kim HJ, Choi YE (2013) Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol 53:1535–1545

    Article  CAS  Google Scholar 

  • Huang Z, Lin J, Cheng Z, Xu M, Huang X, Yang Z, Zheng J (2015) Production of dammarane-type sapogenins in rice by expressing the dammarenediol-II synthase gene from Panax ginseng C.A. Mey. Plant Sci 239:106–114

    Article  CAS  PubMed  Google Scholar 

  • Jia W, Yan H, Bu X, Liu G, Zhao Y (2004) Aglycone protopanaxadiol, a ginseng saponin, inhibits P-glycoprotein and sensitizes chemotherapy drugs on multidrug resistant cancer cells. ASCO Annual Meeting Proceedings (Post-Meeting Edition). J Clin Oncol 22(Suppl):9663

    Article  Google Scholar 

  • Kim SH, Jung SH, Lee YJ, Han JY, Choi YE, Hong HD, Jeon HY, Hwang J, Na S, Kim YM, Ha KS (2015) Dammarenediol-II prevents VEGF-mediated microvascular permeability in diabetic mice. Phytother Res 29:1910–1916

    Article  CAS  PubMed  Google Scholar 

  • Lee MH, Han JY, Kim HJ, Kim YS, Huh GH, Choi YE (2012) Dammarenediol-II production confers TMV tolerance in transgenic tobacco expressing Panax ginseng dammarenediol-II synthase. Plant Cell Physiol 53:173–182

    Article  CAS  PubMed  Google Scholar 

  • Leung KW, Wong AS (2010) Pharmacology of ginsenosides: a literature review. Chin Med 5:20

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Livak KJ, Schmittgen TD (2000) Analysis of relative gene expression data using realtime quantitative PCR and the 2−ΔΔCT method. Methods 25:402–408

    Article  CAS  Google Scholar 

  • Murashige T, Skoog F (1962) A revised medium for rapid growth and bio assays with tobacco tissue cultures. Physiol Plant 15:473–497

    Article  CAS  Google Scholar 

  • PanaGin Pharmaceuticals, Inc (2009) [October 2009]. Further information available at http://www.panagin.com. Accessed May 2019

  • Poehland BL, Carte BK, Francis TA, Hyland LJ, Allaudeen HS (1987) In vitro antiviral activity of dammar resin triterpenoids. J Nat Prod 50:706–713

    Article  CAS  PubMed  Google Scholar 

  • Popovich DG, Kitts DD (2004) Ginsenosides 20(S)-protopanaxadiol and Rh2 reduce cell proliferation and increase sub-G1 cells in two cultured intestinal cell lines (Int-407 and Caco-2). Can J Physiol Pharmacol 82:183–190

    Article  CAS  PubMed  Google Scholar 

  • Qi LW, Wang CZ, Yuan CS (2010) American ginseng: potential structure–function relationship in cancer chemoprevention. Biochem Pharmacol 80:947–954

    Article  CAS  PubMed  Google Scholar 

  • Saklani A, Kutty SK (2008) Plant-derived compounds in clinical trials. Drug Disc Today 13:161–171

    Article  CAS  Google Scholar 

  • Sharma AK, Sharma MK (2009) Plants as bioreactors: recent developments and emerging opportunities. Biotechnol Adv 27:811–832

    Article  CAS  PubMed  Google Scholar 

  • Shibata S (2001) Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 16:S28–S37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thimmappa R, Geisler K, Louveau T, O’Maille P, Osbourn A (2014) Triterpene biosynthesis in plants. Annu Rev Plant Biol 65:225–257

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Wu S, Chappell J (2008) Metabolic engineering of natural products in plants; tools of the trade and challenges for the future. Curr Opin Biotechnol 19:145–152

    Article  CAS  PubMed  Google Scholar 

  • Wu CY, Adach T, Hatano T, Washida H, Suzuki A, Takaiwa F (1998) Promoters of rice seed storage protein genes direct endosperm-specific gene expression in transgenic rice. Plant Cell Physiol 39:885–889

    Article  CAS  Google Scholar 

  • Xu C, Teng J, Chen W, Ge Q, Yang Z, Yu C, Yang Z, Jia W (2010) 20(S)-protopanaxadiol an active ginseng metabolite, exhibits strong antidepressant-like effects in animal tests. Prog Neuropsychopharmacol Biol Psychiatry 34:1402–1411

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from Rural Development Administration, Republic of Korea [Next-Generation BioGreen 21 Program (PJ01369103)].

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Author notes

  1. Jung Yeon Han and So-Hyeon Baek have equally contributed to this work.

Authors and Affiliations

  1. Department of Forest Resources, College of Forest and Environmental Sciences, Kangwon National University, Chuncheon, 200-701, Republic of Korea

    Jung Yeon Han, Hye Jeong Jo & Yong Eui Choi

  2. Department of Well-being Resources, Sunchon National University, 255, Suncheon-si, Jeonnam, 57922, South Korea

    So-Hyeon Baek

  3. Biosafety Division, NAAS, RDA, Jeonju, South Korea

    Do Won Yun

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  1. Jung Yeon Han
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  2. So-Hyeon Baek
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Correspondence to Yong Eui Choi.

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Han, J.Y., Baek, SH., Jo, H.J. et al. Genetically modified rice produces ginsenoside aglycone (protopanaxadiol). Planta 250, 1103–1110 (2019). https://doi.org/10.1007/s00425-019-03204-4

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  • DOI: https://doi.org/10.1007/s00425-019-03204-4

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