Plant Cell, Tissue and Organ Culture (PCTOC)

, Volume 112, Issue 2, pp 159–169 | Cite as

Engineering production of antihypertensive peptides in plants

  • Sergio Rosales-Mendoza
  • Luz María Teresita Paz-Maldonado
  • Dania O. Govea-Alonso
  • Schuyler S. Korban
Review

Abstract

To date, a number of antihypertensive peptides (AHPs) have been identified. Most of these are derived from proteins present in common edible consumables, including milk, egg, and plant foods. Consumption of these foods serves as means of AHP delivery and thus contributing favorable health benefits. It is hypothesized that food crops, either over-expressing AHP precursor proteins or producing particular peptides as heterologous components, may serve as viable vehicles for production and delivery of functional foods as alternative hypertension therapies. In recent years, genetic engineering efforts have been undertaken to add value to functional foods. Pioneering approaches have been pursued in several crop plants, such as rice and soybean. In this review, a summary of current tools used for discovery of new AHPs, as well as strategies and perspectives of capitalizing on these AHPs in genetic engineering efforts will be presented and discussed. The implications of these efforts on the development of functional foods for preventing and treating hypertension are also presented.

Keywords

Hypertension Bioactive peptides Biopharming Transgenic plants 

References

  1. Abubakar A, Saito T, Kitazawa H, Kawai Y, Itoh T (1998) Structural analysis of new antihypertensive peptides derived from cheese whey protein by proteinase K digestion. J Dairy Sci 81:3131–3138Google Scholar
  2. Chen ZY, Peng C, Jiao R, Wong YM, Yang N, Huang Y (2009) Anti-hypertensive nutraceuticals and functional foods. J Agric Food Chem 57:4485–4499PubMedCrossRefGoogle Scholar
  3. Chockalingam A, Campbell NR, Fodor JG (2006) Worldwide epidemic of hypertension. Can J Cardiol 22:553–555PubMedCrossRefGoogle Scholar
  4. Cushman DW, Ondetti MA (1980) Inhibitors of angiotensin-converting enzyme for treatment of hypertension. Biochem Pharmacol 29:1871–1877PubMedCrossRefGoogle Scholar
  5. De Gasparo M, Catt KJ, Inagami T, Wright JW, Unger TH (2000) International union of pharmacology. XXIII. The angiotensin receptors. Pharmacol Rev 52:415–472PubMedGoogle Scholar
  6. De Leo F, Panarese S, Gallerani R, Ceci LR (2009) Angiotensin Converting Enzyme (ACE) inhibitory peptides: production and implementation of functional food. Curr Phar Des 15:3622–3643CrossRefGoogle Scholar
  7. Domon B, Aebersold R (2006) Mass spectrometry and protein analysis. Science 312:212–217PubMedCrossRefGoogle Scholar
  8. Dziuba J, Minkiewicz P, Nalecz D, Iwaniak A (1999) Database of biologically active peptide sequences. Nahrung 43:190–195PubMedCrossRefGoogle Scholar
  9. Erdmann K, Cheung BW, Schröder H (2008) The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease. J Nutr Biochem 19:643–654PubMedCrossRefGoogle Scholar
  10. Erdos EG, Skidgel RA (1997) Metabolism of bradykinin by peptidases in health and disease. In: Farmer SG (ed) The kinin system: handbook of immunopharmacology. Academic Press, London, pp 112–141Google Scholar
  11. Fida HM, Kumada Y, Terashima M, Katsuda T, Katoh S (2009) Tandem multimer expression of angiotensin I-converting enzyme inhibitory peptide in Escherichia coli. Biotechnol J 4:1345–1356PubMedCrossRefGoogle Scholar
  12. FitzGerald RJ, Meisel H (2000) Milk protein-derived peptide inhibitors of angiotensin-I-converting enzyme. Br J Nutr 84:S33–S37PubMedCrossRefGoogle Scholar
  13. FitzGerald RJ, Murray BA, Walsh DJ (2004) Hypotensive peptides from milk proteins. J Nutr 134:980S–988SPubMedGoogle Scholar
  14. Fujita H, Yoshikawa M (1999) LKPNM: a prodrug-type ACE-inhibitory peptide derived from fish protein. Immunopharmacology 44:123–127PubMedCrossRefGoogle Scholar
  15. Fujita H, Usui H, Kurahashi K, Yoshikawa M (1995) Isolation and characterization of ovokinin, a bradykinin B1 agonist peptide derived from ovalbumin. Peptides 16:785–790PubMedCrossRefGoogle Scholar
  16. Fujita H, Yokoyama K, Yoshikawa M (2000) Classification and antihypertensive activity of angiotensin I-converting enzyme inhibitory peptides derived from food proteins. J Food Sci 65:564–569Google Scholar
  17. Gobbetti M, Smacchi E, Corsetti A, Bellucci M (1997) Inhibition of proteolytic enzymes from Pseudomonas fluorescens ATCC 948 and angiotensin I-converting enzyme by peptides from zein, hordein and gluten hydrolysates. J Food Protect 60:499–504Google Scholar
  18. Goossens A, Van Montagu M, Angenon G (1999) Co-introduction of an antisense gene for an endogenous seed storage protein can increase expression of a transgene in Arabidopsis thaliana seeds. FEBS Lett 456:160–164PubMedCrossRefGoogle Scholar
  19. Guang C, Phillips RD (2009) Plant food-derived Angiotensin I converting enzyme inhibitory peptides. J Agric Food Chem 57:5113–5120PubMedCrossRefGoogle Scholar
  20. Gupta N, Bark SJ, Lu WD, Taupenot L, O’Connor DT, Pevzner P, Hook V (2010) Mass spectrometry-based neuropeptidomics of secretory vesicles from human adrenal medullary pheochromocytoma reveals novel peptide products of prohormone processing. J Proteome Res 9:5065–5075PubMedCrossRefGoogle Scholar
  21. Hamamoto H, Sugiyama Y, Nakagawa N, Hashida E, Matsunaga Y, Takemoto S, Watanabe Y, Okada Y (1993) A new tobacco mosaic virus vector and its use for the systemic production of angiotensin-I-converting enzyme inhibitor in transgenic tobacco and tomato. Biotechnology (NY) 11:930–932CrossRefGoogle Scholar
  22. Hansch C, Leo A (1995) Exploring QSAR fundamentals and applications in chemistry and biology. American Chemical Society, WashingtonGoogle Scholar
  23. Hata Y, Yamamoto M, Ohni M, Nakajima K, Nakamura Y, Takano T (1996) A placebo-controlled study of the effect of sour milk on blood pressure in hypertensive subjects. Am J Clin Nutr 64:767–771PubMedGoogle Scholar
  24. Israili ZH, Hernández-Hernández R, Velasco M (2007) The future of antihypertensive treatment. Am J Ther 14:121–134PubMedCrossRefGoogle Scholar
  25. Jauhiainen T, Vapaatalo H, Poussa T, Kyronpalo S, Rasmussen M, Korpela R (2005) Lactobacillus helveticus fermented milk lowers blood pressure in hypertensive subjects in 24-h ambulatory blood pressure measurement. Am J Hypertens 18:1600–1605PubMedCrossRefGoogle Scholar
  26. Jeong DW, Shin DS, Ahn CW, Song IS, Lee HJ (2007) Expression of antihypertensive peptide, His–His-Leu, as tandem repeats in Escherichia coli. J Microbiol Biotechnol 17:952–959PubMedGoogle Scholar
  27. Kanauchi O, Igarashi K, Ogata R, Mitsuyama K, Andoh A (2005) A yeast extract high in bioactive peptides has a blood-pressure lowering effect in hypertensive model. Curr Med Chem 12:3085–3090PubMedCrossRefGoogle Scholar
  28. Karaki H, Doi K, Sugano S, Uchiwa H, Sugai R, Murakami U, Takemoto S (1990) Antihypertensive effect of tryptic hydrolysate of milk casein in spontaneously hypertensive rats. Comp Biochem Physiol C 96:367–371PubMedCrossRefGoogle Scholar
  29. Kawasaki T, Seki E, Osajima K, Yoshida M, Asada K, Matsui T, Osajima Y (2000) Antihypertensive effect of valyl tyrosine, a short chain peptide derived from sardine muscle hydrolyzate, on mild hypertensive subjects. J Hum Hypertens 14:519–523Google Scholar
  30. Kitts DD, Weiler K (2003) Bioactive proteins and peptides from food sources. Applications of bioprocesses used in isolation and recovery. Curr Pharm Des 9:1309–1323PubMedCrossRefGoogle Scholar
  31. Kodera T, Nio N (2006) Identification of an Angiotensin I-converting enzyme inhibitory peptides from protein hydrolysates by a soybean protease and the antihypertensive effects of hydrolysates in spontaneously hypertensive model rats. J Food Sci 71:C164–C173Google Scholar
  32. Lau OS, Sun SS (2009) Plant seeds as bioreactors for recombinant protein production. Biotechnol Adv 27:1015–1022PubMedCrossRefGoogle Scholar
  33. Lehrer SB, Bannon GA (2005) Risks of allergic reactions to biotech proteins in foods: perception and reality. Allergy 60:559–564PubMedCrossRefGoogle Scholar
  34. Luna-Suárez S, Medina-Godoy S, Cruz-Hernández A, Paredes-López O (2010) Modification of the amaranth 11S globulin storage protein to produce an inhibitory peptide of the angiotensin I converting enzyme, and its expression in Escherichia coli. J Biotechnol 148:240–247PubMedCrossRefGoogle Scholar
  35. Maeno M, Yamamoto N, Takano T (1996) Identification of an antihypertensive peptide from casein hydrolysate produced by a proteinase from Lactobacillus helveticus CP790. J Dairy Sci 79:1316–1321PubMedCrossRefGoogle Scholar
  36. Maes W, Van Camp J, Vermeirssen V, Hemeryck M, Ketelslegers JM, Schrezenmeir J, Van Oostveldt P, Huyghebaert A (2004) Influence of the lactokinin Ala-Leu-Pro-Met-His-Ile-Arg (ALPMHIR) on the release of endothelin-1 by endothelial cells. Regul Pept 118:105–109PubMedCrossRefGoogle Scholar
  37. Majumder K, Wu J (2010) A new approach for identification of novel antihypertensive peptides from egg proteins by QSAR and bioinformatics. Food Res Intl 43:1371–1378CrossRefGoogle Scholar
  38. Masuda O, Nakamura Y, Takano T (1996) Antihypertensive peptides are present in aorta after oral administration of sour milk containing these peptides to spontaneously hypertensive rats. J Nutr 126:3063–3068PubMedGoogle Scholar
  39. Matoba N, Doyama N, Yamada Y, Maruyama N, Utsumi S, Yoshikawa M (2001) Design and production of genetically modified soybean protein with anti-hypertensive activity by incorporating potent analogue of ovokinin(2–7). FEBS Lett 18:50–54CrossRefGoogle Scholar
  40. Matsufuji H, Matsui T, Ohshige S, Kawasaki T, Osajima K, Osajima Y (1995) Antihypertensive effects of angiotensin fragments in SHR. Biosci Biotechnol Biochem 59:1398–1401Google Scholar
  41. Matsui T, Li CH, Osajima Y (1999) Preparation and characterization of novel bioactive peptides responsible for angiotensin I-converting enzyme inhibition from wheat germ. J Pept Sci 5:289–297PubMedCrossRefGoogle Scholar
  42. Megias C, Del Mar Yust M, Pedroche J, Lquari H, Giron-Calle J, Alaiz M, Millan F, Vioque J (2004) Purification of an ACE inhibitory peptide after hydrolysis of sunflower (Helianthus annuus L.) protein isolates. J Agric Food Chem 52:1928–1932PubMedCrossRefGoogle Scholar
  43. Miguel M, López-Fandiño R, Ramos M, Aleixandre A (2005) Short-term effect of egg-white hydrolysate products on the arterial blood pressure of hypertensive rats. Brit J Nutr 94:731–737PubMedCrossRefGoogle Scholar
  44. Miyoshi S, Kaneko T, Ishikawa H, Tanaka H, Maruyama S (1995) Production of bioactive peptides from corn endosperm proteins by some proteases. Ann N Y Acad Sci 750:429431CrossRefGoogle Scholar
  45. Möller NP, Scholz-Ahrens KE, Roos N, Schrezenmeir J (2008) Bioactive peptides and proteins from foods: indication for health effects. Eur J Nutr 47:171–182PubMedCrossRefGoogle Scholar
  46. Motoi H, Kodama T (2004) Isolation and characterization of angiotensin I converting enzyme inhibitory peptides from wheat gliadin hydrolysate. Nahrung 47:354–358Google Scholar
  47. Mullally MM, Meisel H, FitzGerald RJ (1997) Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a tryptic fragment of bovine beta-lactoglobulin. FEBS Lett 402:99–101PubMedCrossRefGoogle Scholar
  48. Müntz K (1998) Deposition of storage proteins. Plant Mol Biol 38:77–99PubMedCrossRefGoogle Scholar
  49. Murakami M, Tonouchi H, Takahashi R, Kitazawa H, Kawai Y, Negishi H, Saito T (2004) Structural analysis of a new anti-hypertensive peptide (beta-lactosin B) isolated from a commercial whey product. J Dairy Sci 87:1967–1974Google Scholar
  50. Nakamura Y, Yamamoto N, Sakai K, Takano T (1995) Antihypertensive effect of sour milk and peptides isolated from it that are inhibitors to angiotensin I-converting enzyme. J Dairy Sci 78:1253–1257PubMedCrossRefGoogle Scholar
  51. Nakashita H, Arai Y, Shikanai T, Doi Y, Yamaguchi I (2001) Introduction of bacterial metabolism into higher plants by polycistronic transgene expression. Biosci Biotechnol Biochem 65:1688–1691PubMedCrossRefGoogle Scholar
  52. Nakashima Y, Arihara K, Sasaki A, Mio H, Ishikawa S, Itoh M (2002) Antihypertensive activities of peptides derived from porcine skeletal muscle myosin in spontaneously hypertensive rats. J Food Sci 67:434–437Google Scholar
  53. Nishizawa K, Kita A, Doi C, Yamada Y, Ohinata K, Yoshikawa M, Ishimoto M (2008) Accumulation of the bioactive peptides, novokinin, LPYPR and rubiscolin, in seeds of genetically modified soybean. Biosci Biotechnol Biochem 72:3301–3305Google Scholar
  54. Okamoto K, Aoki K (1963) Development of a strain of spontaneously hypertensive rats. Jpn Circ J 27:282–293PubMedCrossRefGoogle Scholar
  55. Okitsu M, Morita A, Kakitani M, Okada M, Yokogoshi H (1995) Inhibition of the endothelin-converting enzyme by pepsin digests of food proteins. Biosci Biotechnol Biochem 59:325–326PubMedCrossRefGoogle Scholar
  56. Oshima G, Shimabukuro H, Nagasawa K (1979) Peptide inhibitors of angiotensin I-converting enzyme in digests of gelatin by bacterial collagenase. Biochim Biophys Acta 566:128–137PubMedCrossRefGoogle Scholar
  57. Park CJ, Lee JH, Hong SS, Lee HS, Kim SC (1998) High-level expression of the angiotensin-converting-enzyme-inhibiting peptide, YG-1, as tandem multimers in Escherichia coli. Appl Microbiol Biotechnol 50:71–76PubMedCrossRefGoogle Scholar
  58. Peach MJ (1977) Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev 57:313–370PubMedGoogle Scholar
  59. Pihlanto-Leppälä A, Koskinen P, Piilola K, Tupasela T, Korhonen H (2000) Angiotensin I-converting enzyme inhibitory properties of whey protein digests: concentration and characterization of active peptides. J Dairy Res 67:53–64PubMedCrossRefGoogle Scholar
  60. Pripp AH, Isaksson T, Stepaniak L, Sørhaug T (2004) Quantitative structure-activity relationship modelling of ACE nhibitory peptides derived from milk proteins. Eur Food Res Technol 219:579–583CrossRefGoogle Scholar
  61. Pripp AH, Isaksson T, Stepaniak L, Sørhaug T, Ardo Y (2005) Quantitative structure activity relationship modelling of peptides and proteins as a tool in food science. Trends Food Sci Technol 16:484–494CrossRefGoogle Scholar
  62. Quesada-Vargas T, Ruiz ON, Daniell H (2005) Characterization of heterologous multigene operons in transgenic chloroplasts: transcription, processing, and translation. Plant Physiol 138:1746–1762PubMedCrossRefGoogle Scholar
  63. Saito T (2008) Antihypertensive peptides derived from bovine casein and whey proteins. Adv Exp Med Biol 606:295–317PubMedCrossRefGoogle Scholar
  64. Sasaki K, Takahashi N, Satoh M, Yamasaki M, Minamino N (2010) A peptidomics strategy for discovering endogenous bioactive peptides. J Proteome Res 9:5047–5052PubMedCrossRefGoogle Scholar
  65. Seppo L, Jauhiainen T, Poussa T, Korpela R (2003) A fermented milk high in bioactive peptides has a blood pressure-lowering effect in hypertensive subjects. Am J Clin Nutr 77:326–330PubMedGoogle Scholar
  66. Stoger E, Ma JK, Fischer R, Christou P (2005) Sowing the seeds of success: pharmaceutical proteins from plants. Curr Opin Biotechnol 16:167–173PubMedCrossRefGoogle Scholar
  67. Suetsuna K (1998) Isolation and characterization of angiotensin I converting enzyme inhibitor dipeptides derived from Allium sativum L (garlic). J Nutr Biochem 9:415–419CrossRefGoogle Scholar
  68. Tada Y, Utsumi S, Takaiwa F (2003) Foreign gene products can be enhanced by introduction into low storage protein mutants. Plant Biotechnol J 1:411–422PubMedCrossRefGoogle Scholar
  69. Tinoco AD, Saghatelian A (2011) Investigating endogenous peptides and peptidases using peptidomics. Biochemistry 50:7447–7461PubMedCrossRefGoogle Scholar
  70. Vercruysse L, Van Camp J, Smagghe G (2005) ACE inhibitory peptides derived from enzymatic hydrolysates of animal muscle protein: a review. J Agric Food Chem 53:8106–8115PubMedCrossRefGoogle Scholar
  71. Wakasa Y, Zhao H, Hirose S, Yamauchi D, Yamada Y, Yang L, Ohinata K, Yoshikawa M, Takaiwa F (2011) Antihypertensive activity of transgenic rice seed containing an 18-repeat novokinin peptide localized in the nucleolus of endosperm cells. Plant Biotechnol J 9:729–735PubMedCrossRefGoogle Scholar
  72. World Health Organization (2004) Regional consultation on hypertension prevention and controlGoogle Scholar
  73. World Health Organization Regional Office for the Eastern Mediterranean (2006) Guidelines for the management of hypertension in patients with diabetes mellitusGoogle Scholar
  74. Wu J, Aluko RE, Nakai S (2006) Structural requirements of Angiotensin I-converting enzyme inhibitory peptides: quantitative structure activity relationship study of di- and tripeptides. J Agric Food Chem 54:732–738PubMedCrossRefGoogle Scholar
  75. Yamada Y, Matoba N, Usui H, Onishi K, Yoshikawa M (2002) Design of a highly potent anti-hypertensive peptide based on ovokinin(2–7). Biosci Biotechnol Biochem 66:1213–1217PubMedCrossRefGoogle Scholar
  76. Yamamoto N (1997) Antihypertensive peptides derived from food proteins. Inc Biopoly 43:129–134CrossRefGoogle Scholar
  77. Yamamoto N, Akino A, Takano T (1994) Antihypertensive effect of the peptides derived from casein by an extracellular proteinase from Lactobacillus helveticus CP790. J Dairy Sci 77:917–922PubMedCrossRefGoogle Scholar
  78. Yamada Y, Nishizawa K, Yokoo M, Zhao H, Onishi K, Teraishi M, Utsumi S, Ishimoto M, Yoshikawa M (2008) Anti-hypertensive activity of genetically modified soybean seeds accumulating novokinin. Peptides 29:331–337Google Scholar
  79. Yang L, Tada Y, Yamamoto MP, Zhao H, Yoshikawa M, Takaiwa F (2006) A transgenic rice seed accumulating an anti-hypertensive peptide reduces the blood pressure of spontaneously hypertensive rats. FEBS Lett 580:3315–3320PubMedCrossRefGoogle Scholar
  80. Yang LJ, Wakasa Y, Takaiwa F (2008) Biopharming to increase bioactive peptides in rice seed. J AOAC Int 91:957–964PubMedGoogle Scholar
  81. Yano S, Suzuki K, Funatsu G (1996) Isolation from alpha-zein of thermolysin peptides with angiotensin I-converting enzyme inhibitory activity. Biosci Biotechnol Biochem 60:661–663PubMedCrossRefGoogle Scholar
  82. Yoshikawa M, Fujita H, Matoba N, Takenaka Y, Yamamoto T, Yamauchi R, Tsuruki H, Takahata K (2000) Bioactive peptides derived from food proteins preventing lifestyle-related diseases. BioFactors 12:143–146PubMedCrossRefGoogle Scholar
  83. Zhang L, Hao GF, Tan Y, Xi Z, Huang MZ, Yang GF (2009) Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations. Bioorg Med Chem 17:4935–4942PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Sergio Rosales-Mendoza
    • 1
  • Luz María Teresita Paz-Maldonado
    • 2
  • Dania O. Govea-Alonso
    • 1
  • Schuyler S. Korban
    • 3
  1. 1.Laboratorio de Biofarmacéuticos Recombinantes, Facultad de Ciencias QuímicasUniversidad Autónoma de San Luis PotosíSan Luis PotosíMexico
  2. 2.Laboratorio de Ingeniería de Biorreactores, Facultad de Ciencias QuímicasUniversidad Autónoma de San Luis PotosíSan Luis PotosíMexico
  3. 3.Department of Natural Resources and Environmental SciencesUniversity of IllinoisUrbanaUSA

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