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Enrichment of tomato fruit with health-promoting anthocyanins by expression of select transcription factors

Nature Biotechnology volume 26, pages 13011308 (2008) | Download Citation

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Abstract

Dietary consumption of anthocyanins, a class of pigments produced by higher plants, has been associated with protection against a broad range of human diseases. However, anthocyanin levels in the most commonly eaten fruits and vegetables may be inadequate to confer optimal benefits. When we expressed two transcription factors from snapdragon in tomato, the fruit of the plants accumulated anthocyanins at levels substantially higher than previously reported for efforts to engineer anthocyanin accumulation in tomato and at concentrations comparable to the anthocyanin levels found in blackberries and blueberries. Expression of the two transgenes enhanced the hydrophilic antioxidant capacity of tomato fruit threefold and resulted in fruit with intense purple coloration in both peel and flesh. In a pilot test, cancer-susceptible Trp53−/− mice fed a diet supplemented with the high-anthocyanin tomatoes showed a significant extension of life span.

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References

  1. 1.

    & Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339, 1523–1526 (1992).

  2. 2.

    et al. Reversals of age-related declines in neuronal signal transduction, cognitive, motor behavioral deficits with blueberry, spinach, or strawberry dietary supplementation. J. Neurosci. 19, 8114–8121 (1999).

  3. 3.

    et al. Total cranberry extract versus its phytochemical constituents: antiproliferative and synergistic effects against human tumor cell lines. J. Agric. Food Chem. 52, 2512–2517 (2004).

  4. 4.

    et al. Molecular mechanisms behind the chemopreventive effects of anthocyanidins. J. Biomed. Biotechnol. 5, 321–325 (2004).

  5. 5.

    et al. Protective effect of anthocyanins in middle cerebral artery occlusion and reperfusion model of cerebral ischemia in rats. Life Sci. 79, 130–137 (2006).

  6. 6.

    et al. Stimulatory effect of cyanidin 3-glycosides on the regeneration of rhodopsin. J. Agric. Food Chem. 51, 3560–3563 (2003).

  7. 7.

    et al. Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. J. Nutr. 133, 2125–2130 (2003).

  8. 8.

    et al. Superoxide radical scavenging activity of the major polyphenols in fresh plums. J. Agric. Food Chem. 51, 8067–8072 (2003).

  9. 9.

    et al. The anthocyanidins cyanidin and delphinidin are potent inhibitors of the epidermal growth-factor receptor. J. Agric. Food Chem. 49, 958–962 (2001).

  10. 10.

    et al. Flavonoids: antioxidants or signalling molecules? Free Radic. Biol. Med. 36, 838–849 (2004).

  11. 11.

    et al. Overexpression of petunia chalcone isomerase in tomato results in fruit containing increased levels of flavonols. Nat. Biotechnol. 19, 470–474 (2001).

  12. 12.

    et al. Biomarkers of antioxidant capacity in the hydrophilic and lipophilic compartments of human plasma. Arch. Biochem. Biophys. 430, 97–103 (2004).

  13. 13.

    et al. Molecular aspects of Anthocyanin fruit tomato in relation to high pigment-1. J. Hered. 99, 292–303 (2008).

  14. 14.

    et al. Fruit-specific RNAi-mediated suppression of DET1 enhances carotenoid and flavonoid content in tomatoes. Nat. Biotechnol. 23, 890–895 (2005).

  15. 15.

    & Progress in plant metabolic engineering. Proc. Natl. Acad. Sci. USA 98, 8925–8927 (2001).

  16. 16.

    Transcription factors and the manipulation of plant trais. Curr. Opin. Biotechnol. 7, 130–138 (1996).

  17. 17.

    et al. Activation tagging in tomato identifies a transcriptional regulator of anthocyanin biosynthesis, modification, and transport. Plant Cell 15, 1689–1703 (2003).

  18. 18.

    et al. High-flavonol tomatoes resulting from the heterologous expression of the maize transcription factor genes Lc and C1. Plant Cell 14, 2509–2526 (2002).

  19. 19.

    et al. Control of anthocyanin biosynthesis in flowers of Antirrhinum majus. Plant J. 1, 37–49 (1991).

  20. 20.

    et al. A small family of MYB-regulatory genes controls floral pigmentation intensity and patterning in the genus Antirrhinum. Plant Cell 18, 831–851 (2006).

  21. 21.

    Coordinate genetic regulation of flavanoid biosynthetic enzyme in maize. Mol. Gen. Genet. 67, 345–355 (1983).

  22. 22.

    et al. Regulatory genes controlling anthocyanin pigmentation are functionally conserved among plant species and have distinct sets of target genes. Plant Cell 5, 1497–1512 (1993).

  23. 23.

    et al. A common gene regulates pigmentation pattern in diverse plant species. Cell 68, 955–964 (1992).

  24. 24.

    & The tomato E8 gene influences ethylene biosynthesis in fruit but not in flowers. Plant Physiol. 112, 537–547 (1996).

  25. 25.

    et al. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumors. Nature 356, 215–221 (1992).

  26. 26.

    et al. Tumor spectrum analysis in p53-mutant mice. Curr. Biol. 4, 1–7 (1994).

  27. 27.

    et al. The antioxidant function of the p53 tumor suppressor. Nat. Med. 11, 1306–1313 (2005).

  28. 28.

    et al. Altered regulation of tomato and tobacco pigmentation genes caused by the delila gene of Antirrhinum. Plant J. 7, 333–339 (1995).

  29. 29.

    et al. Quantitative relationship between phenylalanine ammonia-lyase levels and phenylpropanoid accumulation in transgenic tobacco identifies a rate-determining step in natural product synthesis. Proc. Natl. Acad. Sci. USA 91, 7608–7612 (1994).

  30. 30.

    Fruits and vegetables in the prevention of cellular oxidative damage. Am. J. Clin. Nutr. 78 Suppl, 570S–578S (2003).

  31. 31.

    & Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: cause, consequence, or epiphenomenon? Free Radic. Biol. Med. 41, 1727–1746 (2006).

  32. 32.

    et al. Chronic dietary intake of plant-derived anthocyanins protects the rat heart against ischemia-reperfusion injury. J. Nutr. 138, 747–752 (2008).

  33. 33.

    Regulation of adipocyte function by anthocyanins; possibility of preventing the metabolic syndrome. J. Agric. Food Chem. 56, 642–646 (2008).

  34. 34.

    Red berries and their health benefits. Nutraceutical beverages: chemistry, nutrition, and health effects. in Nutraceutical Beverages: Chemistry, Nutrition, and Health Effects ACS Symp. ser. 871 (ed. Fereidoon, S.) 123–132, (American Chemical Society, Washington, DC, 2004).

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Acknowledgements

We thank Andrew Davis for photography and David Hopwood for comments on the manuscript. This work was supported by the EU FP5 PROFOOD project (QLK1-CT-2001-01080) awarded to A.G.B., R.D.H., H.-P.M. and C.M.; by the EU FP6 FLORA project (FOOD-CT-01730) awarded to H.-P.M., R.D.H., M.G. and C.M.; by the Centre for Biosystems Genomics as part of the Netherlands Genomic Initiative which supports A.G.B. and R.D.H.; and by the core strategic grant of the Biological and Biotechnological Science Research Council (BBSRC) to JIC, which supports C.M.

Author information

Affiliations

  1. John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK.

    • Eugenio Butelli
    • , Jie Luo
    •  & Cathie Martin
  2. Experimental Oncology Dept., European Institute of Oncology, Via Adamello 16, Milano, Italy.

    • Lucilla Titta
    •  & Marco Giorgio
  3. Leibniz Institute of Plant Genetics and Crop Plant Research, Corrensstrasse 3, D-06466 Gatersleben, Germany.

    • Hans-Peter Mock
    • , Andrea Matros
    •  & Silke Peterek
  4. Plant Research International, Business Unit Bioscience, PO Box 16, 6700 AA Wageningen, The Netherlands.

    • Elio G W M Schijlen
    •  & Arnaud G Bovy
  5. Centre for BioSystems Genomics, PO Box 98, 6700 AB Wageningen, The Netherlands.

    • Robert D Hall

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Contributions

E.B. assembled the constructs for transformation, undertook the transformation experiments, performed all of the molecular biological analysis and contributed to the planning and writing of the paper. L.T. and M.G. performed the animal experiments with mice. H.-P.M., A.M. and S.P. performed the phenolic analysis and identification and contributed to writing the manuscript. E.G.W.M.S., R.D.H. and A.G.B. prepared the PROFOOD tomato microarray, undertook the comparative expression profiling and the comparative HPLC analysis in the different transgenic lines. J.L. performed HPLC analysis in the different transgenic lines. C.M. planned and designed the project and contributed to the writing of the manuscript.

Corresponding author

Correspondence to Cathie Martin.

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DOI

https://doi.org/10.1038/nbt.1506

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