Biologia plantarum 52:423-428, 2008 | DOI: 10.1007/s10535-008-0086-4

Production of recombinant human lactoferrin from transgenic plants

G. Stefanova1,*, M. Vlahova1, A. Atanassov1
1 AgroBioInstitute, Sofia, Bulgaria

Molecular farming provides a powerful tool for low cost production of recombinant proteins with pharmaceutical value. The use of transgenic plants has been increasingly tested as alternative system for obtaining biologically active human lactoferrin in plants. Precise selection of plant species, transformation techniques and expression cassettes, in addition to conduction of detailed glycosylation and immunogenicity studies, serves as basis of obtaining safe recombinant human lactoferrin in high concentrations for the use of pharmacy. On the other hand, expression of antimicrobial protein lactoferrin in plants is a promising opportunity for crop quality improvement by increasing plant disease resistance.

Keywords: gene expression; molecular farming; plant-produced pharmaceutically important substances
Subjects: immunoblotting; Lycopersicon esculentum; Nicotiana tabacum; proteins; tobacco; tomato; transgenic plants

Received: October 2, 2007; Accepted: May 2, 2008; Published: September 1, 2008Show citation

ACS AIP APA ASA Harvard Chicago IEEE ISO690 MLA NLM Turabian Vancouver
Stefanova, G., Vlahova, M., & Atanassov, A. (2008). Production of recombinant human lactoferrin from transgenic plants. Biologia plantarum, 52(3), 423-428. doi: 10.1007/s10535-008-0086-4.
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)

    • Open full article

    References

    1. Anzai, H., Takaiwa, F., Katsumata, K.: Production of human lactoferrin in transgenic plants.-In: Shimazaki, K., Tsuda, H., Tomita, M., Kuwata, T., Perraudin, J.-P. (ed.): Lactoferrin: Structure, Function and Applications. Pp. 265-271. Elsevier, Amsterdam 2000.
    2. Arakawa, T., Chong, D.K.X., Langridge, W.H.R.: Efficacy of a food plant based oral cholera toxin B subunit vaccine.-Nature Biotechnol. 16: 292-297, 1998. Go to original source...
    3. Bardor, M., Faveeuw, C., Fitchette, A.-C., Gilbert, D., Galas, L., Trottein, F., Faye, L., Lerouge P.: Immunoreactivity in mammals of two typical plant glyco-epitopes, core α(1,3)-fucose and core xylose.-Glycobiology 13: 427-434, 2003. Go to original source...
    4. Bardor, M., Loutelier-Bourhis, C., Paccalet, T., Cosette, P., Fitchette, A.-C., Vézina, L.-P., Trépanier, S., Dargis, M., Lemieux, R., Lange, C., Faye, L., Lerouge, P.: Monoclonal C5-1 antibody produced in transgenic alfalfa plants exhibits a N-glycosylation that is homogenous and suitable for glycol-engineering into human-compatible structures.-Plant Biotechnol. J. 1: 451-462, 2003. Go to original source...
    5. Bříza, J., Pavingerová, D., Vlasák J., Ludvíková, V., Niedermeierová, H.: Production of human papillomavirus type 16 E7 oncoprotein fused with β-glucuronidase in transgenic tomato and potato plants.-Biol. Plant. 51: 268-276, 2007.
    6. Busse, U., Levée, V., Trépanier, S., Vézina, L.-P.: Production of antibodies in alfalfa (Medicago sativa).-In: Erickson L. (ed.): Molecular Farming of Plants and Animal for Human and Veterinary Medicine. Pp. 199-219. J. Wiley & Sons, New York 2001.
    7. Chen, M., Liu, X., Wang, Z., Song, J., Qi, Q., Wang, P.G.: Modification of Plant N-glycans processing: the future of producing therapeutic protein by transgenic plants.-Med. Res. Rev. 25: 343-360, 2005. Go to original source...
    8. Choi, S.-M., Lee, O.-S., Kwon, S.-Y., Kwak, S.-S., Yu, D.-Y., Lee, H.-S.: High expression of a human lactoferrin in transgenic tobacco cell cultures.-Biotechnol. Lett. 25: 213-218, 2003. Go to original source...
    9. Chong, D.K.X., Langridge, W.H.R.: Expression of full-length bioactive antimicrobal human lactoferrin in potato plants.-Transgenic Res. 9: 71-78, 2000. Go to original source...
    10. D'Aoust, M.-A., Lerouge, P., Busse, U., Bilodeau, P., Trépanier, S., Gomord, V., Faye, L., Vézina, L-P.: Efficient and reliable production of pharmaceuticals in alfalfa.-In: Fischer, R., Schillberg, S. (ed.): Molecular Farming. Pp. 1-12. Wiley-VCH-Verlag, Weinheim 2004. Go to original source...
    11. Damiens, E., Mazurier, J., El Yazidi, I., Masson, M., Duthille, I., Spik, G., Boilly-Marer, Y.: Effects of human lactoferrin on NK cell cytotoxicity against haematopoietic and epithelial tumor cells.-Biochim. biophys. Acta 1402: 277-287, 1998. Go to original source...
    12. Fischer, R., Emans, N., Schuster, F., Hellwig, S., Drossard, J.: Towards molecular farming in the future: using plant cell-suspension cultures as bioreactor.-Biotechnol. appl. Biochem. 30: 109-112, 1999.
    13. Fischer, R., Stoger, E., Schillberg, S., Christou, P., Twyman, R.M.: Plant-based productions of biopharmaceuticals.-Curr. Opin. Plant Biol. 7: 152-158, 2004.
    14. Hendrixson, D.R., Qiu, J., Shewry, S.C., Fink, D.L., Petty, S., Baker, E.N., Plaut, A.G., Geme III, J.W.St.: Human milk lactoferrin is a serine protease that cleaves Haemophilus surface proteins at arginine-rich sites.-Mol. Microbiol. 47: 607-617, 2003. Go to original source...
    15. Horn, M.E., Woodard, S.L., Howard, J.A.: Plant molecular farming: systems and products.-Plant Cell Rep. 22: 711-720, 2004.
    16. Kamenarova, K., Gecheff, K., Stoyanova, M., Muhovski, Y., Anzai, H., Atanassov, A.: Production of recombinant human lactoferrin in transgenic barley.-Biotechnol. Biotechnol. Eq. 21: 18-27, 2007. Go to original source...
    17. Kanyshkova, T.G., Babina, S.E., Semenov, D.V., Isaeva, N., Vlassov, A.V., Neustroev, K.N., Kul'minskaya, A.A., Buneva, V.N., Nevinsky, G.A.: Multiple enzymic activities of human milk lactoferrin.-Eur. J. Biochem. 270: 3353-3361, 2003.
    18. Kawakami, H., Lönnerdal, B.: Isolation and function of a receptor for human lactoferrin in human fetal intestinal brush-border membranes.-Amer. J. Physiol. 261: G841-G846, 1991. Go to original source...
    19. Krimpenfort, P.: The production of human lactoferrin in the milk of transgenic animals.-Cancer Detect Prev. 17: 301-305, 1993.
    20. Kwon, S.Y., Jo, S.H., Lee, O.S., Choi, S.M., Kwak, S.S., Lee, H.S.: Transgenic ginseng cell lines that produse high levels of a human lactoferrin.-Planta med. 69: 1005-1008, 2003.
    21. Lee, T.-J., Coyne, P.P., Clemente, T.E., Mitra, A.: Partial resistance to bacterial wilt in transgenic tomato plants expressing antibacterial Lactoferrin gene.-J. amer. Soc. hort. Sci. 127: 158-168, 2002. Go to original source...
    22. Liang, Q., Richardson, T.: Expression and characterization of human lactoferrin in yeast Saccharomyces cerevisiae.-J. Agr. Food Chem. 41: 1800-1807, 1993.
    23. Liu, J.R., Lee, M.H., Lee, S.H., Yu, D.-Y., Lee, K.-K., Chung, W.-I.: Expression of human lactoferrin gene in transgenic tobacco plants: feasibility of virus resistance.-In: Proceedings of the 1st Japan Korea Joint Seminar on the Production of Recombinant Proteins and Transgenic Animals in Present and Future. Pp. 39-45. 1996.
    24. Liu, T., Zhang, Y.-Z., Wu, X.-F.: High level expression of functionally active human lactoferrin in silkworm larvae.-J. Biotechnol. 118: 246-256, 2005. Go to original source...
    25. Lönnerdal, B.: Expression of human milk proteins in plants.-J. amer. Coll. Nutr. 21: 218S-221S, 2002. Go to original source...
    26. Mason, H.S., Lam, D.M.K., Arntzen, C.J.: Expression ot hepatitis B surface antigen in transgenic plants.-Proc. nat. Acad. Sci. USA 89: 11745-11749, 1992. Go to original source...
    27. Min, S.R., Woo, J.W., Jeong, W.J., Han, S.K., Lee, Y.B., Liu, J.R.: Production of human lactoferrin in transgenic cell suspension cultures of sweet potato.-Biol. Plant. 50: 131-134, 2006. Go to original source...
    28. Mitra, A., Zhang, Z.: Expression of a human lactoferrin cDNA in tobacco cells produces antibacterial protein(s).-Plant Physiol. 106: 977-981, 1994. Go to original source...
    29. Nandi, S., Suzuki, Y.A., Huang, J., Yalda, D., Pham, P., Wu, L., Bartley, G., Huang, N., Lönnerdal, B.: Expression of human lactoferrin in transgenic rice grains for the application in infant formula.-Plant Sci. 163: 713-722, 2002. Go to original source...
    30. Naot, D., Grey, A., Reid, I.R., Cornish, J.: Lactoferrin - A novel bone growth factor.-Clin. med. Res. 3: 93-101, 2005. Go to original source...
    31. Nuijens, J.H., Van Berkel, P.H., Geerts, M.E., Hartevelt, P.P., De Boer, H.A., Van Veen, H.A., Pieper, F.R.: Characterization of recombinant human lactoferrin secreted in milk of transgenic mice.-J. biol. Chem. 272: 8802-8807, 1997. Go to original source...
    32. Platenburg, G.J., Kootwijk, E.P., Kooiman, P.M., Woloshuk, S.L., Nuijens, J.H., Krimpenfort, P.J., Pieper, F.R., De Boer, H.A., Strijker, R.: Expressiom of human lactoferrin in milk of transgenic mice.-Transgenic Res. 3: 99-108, 1994. Go to original source...
    33. Salmon, V., Legrand, D., Slomianny, M.-C., Yazidi, I.E., Spik, G., Gruber, V., Bournat, P., Olagnier, B., Mison, D., Theisen, M., Mérot, B.: Production of human lactoferrin in transgenic tobacco plants.-Protein Exp. Purif. 13: 127-135, 1998. Go to original source...
    34. Samyn-Petit, B., Dubos, J.-P.W., Chirat, F., Coddeville, B., Demaizieres, G., Farrer, S., Slomianny, M.-C., Theisen, M., Delannoy, P.: Comparative analysis of the site-specific N-glycosylation of human lactoferrin produced in maize and tobacco plants.-Eur. J. Biochem. 270: 3235-3242, 2003.
    35. Samyn-Petit, B., Gruber, V., Flahaut, C., Wajda-Dubos, J.-P., Farrer, S., Pons, A., Desmaizieres, G., Slomianny, M.-C., Theisen, M., Delannoy, P.: N-glycosylation potential of maize: the human lactoferrin used as a model.-Glycoconjucate J. 18: 519-527, 2001. Go to original source...
    36. Spik, G., Theisen, M.: Characterization of the post-translational biochemical processing of human lactoferrin expressed in transgenic tobacco.-Bundesgesundheitsblatt-Gesundheitsforsch-Gesundheitsschutz 43: 104-109, 2000. Go to original source...
    37. Stoger, E., Ma, J.K.-C., Fischer, R., Christou, P.: Sowing the seeds of success: pharmaceutical proteins from plants.-Current Opin. Biotechnol. 16: 167-173, 2005. Go to original source...
    38. Stowell, K.M., Rado, T.A., Funk, W.D., Tweedie, J.W.: Expression of cloned human lactoferrin in baby-hamster kidney cells.-Biochem. J. 276: 349-355, 1991. Go to original source...
    39. Sunil Kumar, G.B., Ganapathi, T.R., Srinivas, L., Revathi, C.J., Bapat, V.A.: Hepatitis B surface antigen expression in NT-1 cells of tobacco using different expression cassettes.-Biol. Plant. 51: 467-471, 2007. Go to original source...
    40. Takase, K., Hagiwara, K., Onodera, H., Nishizawa, Y., Ugaki, M., Omura, T., Numata, S., Akutsu, K., Kumura, H., Shimazaki, K.: Constitutive expression of human lactoferrin and its N-lobe in rice plants to confer disease resistance.-Biochem. Cell Biol. 83: 239-249, 2005.
    41. Twyman, R.M., Stoger, E., Schillberg, S., Christou, P., Fischer, R.: Molecular pharming in plants: host systems and expression technology.-Trends Biotechnol. 21: 570-577, 2003. Go to original source...
    42. Van Berkel, P.H., Geerts, M.E., Van Veen, H.A., Kooiman, P.M., Pieper, F.R., De Boer, H.A., Nuijens, J.H.: Glycosylated and unglycosylated human lactoferrin both bind iron and show identical affinities towards human lysozyme and bacterial lipopolysaccharide, but differ in their susceptibilities towards tryptic proteolysis.-Biochem. J. 312: 107-114, 1995. Go to original source...
    43. Van Berkel, P.H., Nuijens, J.H., Van Veen, H.A., Abrahams, J.P., Thomassen, E.A.J. The protein structure of recombinant human lactoferrin produced in the milk of transgenic cows closely matches the structure of human milk-derived lactoferrin.-Transgenic Res. 14: 397-405, 2005. Go to original source...
    44. Van der Strate, B.W.A., Beljaars, L., Molema, G., Harmsen, M.C., Meijer, D.K.F.: Antiviral activities of lactoferrin.-Antiviral Res. 52: 225-239, 2001. Go to original source...
    45. Ward, P.P., Lo, J.Y., Duke, M., May, G.S., Headon, D.R., Conneely, O.M.: Production of biologically active recombinant human lactoferrin in Aspergillus orizae.-Bio/Technology 10: 784-789, 1992.
    46. Ward, P.P., Piddington, C.S., Cunningham, G.A., Zhou, X., Wyatt, R.D., Conneely, O.M.: A system for production of commercial quantities of human lactoferrin: a broad spectrum natural antibiotic.-Biotechnology 13: 498-503, 1995. Go to original source...
    47. Yamauchi, K., Tomita, M., Giehl, T.J., Ellison, R.T.: Antibacterial activity of lactoferrin and a pepsin derived lactoferrine peptide fragment.-Infect. Immun. 61: 719-728, 1993.
    48. Zhang, Z., Coyne, D.P., Vidaver, A.K., Mitra, A.: Expression of human lactoferrin cDNA confers resistance to Ralstonia solanacearum in transgenic tobacco plants.-Phytopathology 88: 730-734, 1998. Go to original source...

    Return to the content