17 Glycan Engineering in Transgenic Plants
Annual Plant Reviews book series, Volume 41: Plant Polysaccharides
Muriel Bardor,
José A. Cremata,
Patrice Lerouge,
Muriel Bardor
Université de Rouen, UPRES-EA 4358, IFRMP 23, Mont Saint Aignan Cédex, 76821 France
Search for more papers by this authorJosé A. Cremata
CIGB, Department of Carbohydrate Chemistry, Havana, Cuba
Search for more papers by this authorPatrice Lerouge
Université de Rouen, UPRES-EA 4358, IFRMP 23, Mont Saint Aignan Cédex, 76821 France
Search for more papers by this authorMuriel Bardor,
José A. Cremata,
Patrice Lerouge,
Muriel Bardor
Université de Rouen, UPRES-EA 4358, IFRMP 23, Mont Saint Aignan Cédex, 76821 France
Search for more papers by this authorJosé A. Cremata
CIGB, Department of Carbohydrate Chemistry, Havana, Cuba
Search for more papers by this authorPatrice Lerouge
Université de Rouen, UPRES-EA 4358, IFRMP 23, Mont Saint Aignan Cédex, 76821 France
Search for more papers by this authorThis article was originally published in 2011 in Plant Polysaccharides, Volume 41 (ISBN 9781405181723) of the Annual Plant Reviews book series, this volume edited by Peter Ulvskov. The article was republished in Annual Plant Reviews online in April 2018.
Manuscript received October 2008
Abstract
N-glycosylation is a major post-translational modification step in the biosynthesis of proteins in eukaryotes. This process consists of two main steps, the early N-glycan processing occurring in the endoplasmic reticulum and its maturation in the Golgi apparatus. The early N-glycan processing steps are conserved among eukaryotes and are involved in the quality control of proteins. In contrast, the maturation steps in the Golgi apparatus give rise to a large variety of organism-specific complex structures. This divergence in the resulting N-glycan structures is a key issue when the plant is used as a cell factory for the production of human therapeutic proteins. In this chapter, we describe the main aspects of the N-glycan biosynthesis in plants as well as strategies that have been developed to engineer this N-glycosylation pathway in order to allow the production in transgenic plants of pharmaceutical proteins that carry human-like glycans.
References
- Aalberse, R.C., Koshte, V., Clemens, J.G. (1981) Immunoglobulin E antibodies that crossreact with vegetable foods, pollen, and Hymenoptera venom. Journal of Allergy and Clinical Immunology, 68, 356–364.
- Angatta, T., Varki, A. (2002) Chemical diversity in the sialic acids and related a-keto acids: an evolutionary perspertive. Chemical Review, 102, 439–469.
- Bakker, H., Bardor, M., Molthoff, J.W., et al. (2001) Galactose-extended glycans of antibodies produced by transgenic plants. Proceedings of the National Academy of Sciences of the U S A, 98, 2899–2904.
- Bakker, H., Rouwendal, G.J., Karnoup, A.S., et al. (2006) An antibody produced in tobacco expressing a hybrid beta-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes. Proceedings of the National Academy of Sciences of the U S A, 103, 7577–7582.
-
Bardor, M.,
Loutelier-Bourhis, C.,
Paccalet, T., et al.
(2003a)
Monoclonal C5–1 antibody produced in alfalfa plants exhibits a N-glycosylation that is homogenous and suitable for glyco-engineering into human-compatible structures.
Plant Biotechnology Journal,
1,
451–462.
10.1046/j.1467-7652.2003.00041.x Google Scholar
- Bardor, M., Faveeuw, C., Fitchette, A.C., et al. (2003b) Immunoreactivity in mammals of two typical plant glyco-epitopes, core α(1,3)-fucose and core xylose. Glycobiology, 13, 427–434.
- Burda, P., Aebi, M. (1999) The dolichol pathway of N-linked glycosylation. Biochimica et Biophysica Acta, 1426, 239–257.
- Cabanes-Macheteau, M., Fitchette-Laine, A.C., Loutelier-Bourhis, C., et al. (1999) N-glycosylation of a mouse IgG expressed in transgenic tobacco plants. Glycobiology, 9, 365–372.
- Cabrera, G., Cremata, J.A., Valdés, R., et al. (2004) Influence of culture conditions on the N-glycosylation of a monoclonal antibody specific for recombinant hepatitis B surface antigen. Biotechnology and Applied Biochemistry, 40, 1–10.
- Cox, K.M., Sterling, J.D., Regan, J.T., et al. (2006) Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nature Biotechnology, 24, 1591–1597.
-
Downing, W.L.,
Galpin, J.D.,
Clemens, S., et al.
(2006)
Synthesis of enzymatically active human alpha-L-iduronidase in Arabidopsis cgl (complex glycan-deficient) seeds.
Plant Biotechnology Journal,
4,
169–181.
10.1111/j.1467-7652.2005.00166.x Google Scholar
- Dunkley, T.P.J., Hester, S., Shadforth, I.P., et al. (2006) Mapping the Arabidopsis organelle proteome. Proceedings of the National Academy of Sciences of the U S A, 103, 6518–6523.
- Elbers, I.J.W., Stoopen, G.M., Bakker, H., et al. (2001) Influence of growth conditions and developmental stage on N-glycan heterogeneity of transgenic immunoglobulin G and endogenous proteins in tobacco leaves. Plant Physiology, 126, 1314–1322.
- Faye, L., Chrispeels, M.J. (1988) Common antigenic determinants in the glycoproteins of plants, molluscs and insects. Glycoconjugate Journal, 5, 245–256.
- Faye, L., Gomord, V., Fitchette-Lainé, A.-C., Chrispeels, M.J. (1993) Affinity purification of antibodies specific for Asn-linked glycans containing alpha 1-3 fucose or beta 1-2 xylose. Analytical Biochemistry, 209, 104–108.
- Fischer, R., Stoger, E., Schillberg, S., Christou, P., Twyman, R.M. (2004) Plant-based production of biopharmaceuticals. Current Opinion in Plant Biology, 7, 152–158.
- Fitchette-Lainé, A.C., Gomord, V., Chekkafi, A., Faye, L. (1994) Distribution of xylosylation and fucosylation in the plant Golgi apparatus. Plant Journal, 5, 673–682.
-
Fitchette-Lainé, A.C.,
Gomord, V.,
Cabanes, M., et al.
(1997)
N-glycans harbouring the Lewis a epitope are expressed at the surface of plant cells.
Plant Journal,
12,
1411–1417.
10.1046/j.1365-313x.1997.12061411.x Google Scholar
- Garcia-Casado, G., Sanchez-Monge, R., Chrispeels, M.J., Armentia, A., Salcedo, G., Gomez, L. (1996) Role of complex asparagine-linked glycans in the allergenicity of plant glycoproteins. Glycobiology, 6, 471–477.
-
Gomord, V.,
Sourrouille, C.,
Fitchette, A.C., et al.
(2004)
Production and glycosylation of plant-made pharmaceuticals: the antibodies as a challenge.
Plant Biotechnology Journal,
2,
83–100.
10.1111/j.1467-7652.2004.00062.x Google Scholar
- Harduin-Lepers, A., Mollicone, R., Delannoy, P., Oriol, R. (2005) The animal sialyltransferases and sialyltransferase-related genes: A phylogenetic approach. Glycobiology, 15, 805–817.
- Helenius, A., Aebi, M. (2001) Intracellular functions of N-linked glycans. Science, 291, 2364–2369.
- Hiatt, A.C., Cafferkey, R., Bowdish, K. (1989) Production of antibodies in transgenic plants. Nature, 342, 76–78.
-
Huether, C.M.,
Lienhart, O.,
Baur, A., et al.
(2005)
Glyco-engineering of moss lacking plant-specific sugar residues.
Plant Biology,
7,
292–299.
10.1055/s-2005-837653 Google Scholar
- Jefferis, R. (2005) Glycosylation of recombinant antibody therapeutics. Biotechnology Progress, 21, 11–16.
- Johnson, K.D., Chrispeels, M.J. (1987) Substrate specificities of N-acetylglucosaminyl, fucosyl-, and xylosyltransferases that modify glycoproteins in the Golgi apparatus of bean cotyledons. Plant Physiology, 84, 1301–1308.
- Kelm, S., Schauer, R. (1997) Sialic acids in molecular and cellular interactions. International Review of Cytologyl, 175, 137–240.
- Ko, K., Tekoah, Y., Rudd, P.M., et al. (2003) Function and glycosylation of plant-derived antiviral monoclonal antibody. Proceedings of the National Academy of Sciences of the U S A, 100, 8013–8018.
-
Koprivova, A.,
Stemmer, C.,
Altmann, F., et al.
(2004)
Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans.
Plant Biotechnology Journal,
2,
517–523.
10.1111/j.1467-7652.2004.00100.x Google Scholar
- Kurosaka, A., Yano, A., Itoh, N., Kuroda, Y., Nakagawa, T., Kawasaki, T. (1991) The structure of a neural specific carbohydrate epitope of horseradish peroxidase recognized by anti-horseradish peroxidase antiserum. The Journal of Biological Chemistry, 266, 4168–4172.
-
Leiter, H.,
Mucha, J.,
Staudacher, E.,
Grimm, R.,
Glössl, J.,
Altmann, F.
(1999)
Purification, cDNA cloning, and expression of GDP-L-Fuc: Asn-linked GlcNAc α1,3-fucosyltransferase from mung beans.
Journal of Biological Chemistry,
274,
21830–21839.
10.1074/jbc.274.31.21830 Google Scholar
- Lerouge, P., Cabanes-Macheteau, M., Rayon, C., Fitchette-Laine, A.C., Gomord, V., Faye, L. (1998) N-glycoprotein biosynthesis in plants: recent developments and future trends. Plant Molecular Biology, 38, 31–48.
- Ma, J.K.C., Chikwamba, R., Sparrow, P., Fischer, R., Mahoney, R., Twyman, R.M. (2005) Plant-derived pharmaceuticals – the road forward. Trends in Plant Science, 10, 580–585.
- Matsumoto, S., Ikura, K., Ueda, M., Sasaki, R. (1995) Characterization of a human glycoprotein (erythropoietin) produced in cultured tobacco cells. Plant Molecular Biology, 27, 1163–1172.
- McManus, M.T., Mc Keating, J., Secher, D.S., et al. (1988) Identification of a monoclonal antibody to abscission tissue that recognises xylose/fucose-containing N-linked oligosaccharides from higher plants. Planta, 175, 506–512.
- Mimura, Y., Church, S., Ghirlando, R., et al. (2000) The influence of glycosylation on the thermal stability and effector function expression of human IgG1-Fc: properties of a series of truncated glycoforms. Molecular Immunology, 7, 697–706.
- Misaki, R., Fujiyama, K., Seki, T. (2006) Expression of human CMP-N-acetyneuraminic acid synthetase and CMP-sialic acid transporter in tobacco suspension-cultured cell. Biochemical and Biophyical Research Communications, 339, 1184–1189.
- Nose, M., Wigzell, H. (1983) Biological significance of carbohydrate chains on monoclonal antibodies. Proceedings of the National Academy of Sciences of the U S A, 80, 6632–6636.
-
Paccalet, T.,
Bardor, M.,
Rihouey, C., et al.
(2007)
Engineering of a sialic acid synthesis pathway in transgenic plants by expression of bacterial Neu5Ac-synthesizing enzymes.
Plant Biotechnology Journal,
5,
12–25.
10.1111/j.1467-7652.2006.00211.x Google Scholar
- Palacpac, N.Q., Yoshida, S., Sakai, H., et al. (1999) Stable expression of human beta 1,4-galactosyltransferase in plant cells modifies N-linked glycosylation patterns. Proceedings of the National Academy of Sciences of the U S A, 96, 4692–4697.
- Petrucelli, S., Otegui, M.S., Lareu, F., et al. (2006) A KDEL-tagged monoclonal antibody is efficiently retained in the endoplasmic reticulum in leaves, but is both partially secreted and sorted to protein storage vacuoles in seeds. Plant Biotechnology Journal, 4, 511–527.
- Raju, T.S., Briggs, J.B., Borge, S.M., Jones, A.J.S. (2000) Species-specific variation in glycosylation of IgG : evidence for the species-specific sialylation and branch-specific galactosylation and importance for engineering recombinant glycoprotein therapeutics. Glycobiology, 10, 477–486.
- Ramirez, N., Rodriguez, M., Ayala, M., et al. (2003) Expression and characterization of an anti-(hepatitis B surface antigen) glycosylated mouse antibody in transgenic tobacco (Nicotiana tabacum) plants and its use in the immunopurification of its target antigen. Biotechnology and Applied Biochemistry, 38, 223–230.
- Rayon, C., Cabanes-Macheteau, M., Loutelier-Bourhis, C., et al. (1999) Characterization of N-glycans from Arabidopsis thaliana. Application to a fucose-deficient mutant. Plant Physiology, 119, 725–733.
- Rouwendal, G.J.A., Wuhrer, M., Florack, D.E.A., et al. (2007) Efficient introduction of a bisecting GlcNAc residue in tobacco N-glycans by expression of the gene encoding human N-acetylglucosaminyltransferase III. Glycobiology, 17, 334–344.
- Rudd, P.M., Leatherbarrow, R.J., Rademacher, T.W., Dwek, R.A. (1991) Diversification of the IgG molecule by oligosaccharides. Molecular Immunology, 28, 1369–1378.
- Schahs, M., Strasser, R., Stadlmann, J., Kunert, R., Rademacher, T., Steinkellner, H. (2007) Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnology Journal, 5, 657–663.
- Séveno, M., Bardor, M., Paccalet, T., Gomord, V., Lerouge, P., Faye, L. (2004) Glycoprotein sialylation in plants? Nature Biotechnology, 22, 5–6.
- Shah, M.M., Fuliyama, K., Flynn, C.R., Joshi, L. (2003) Sialylated endogenous glycoconjugates in plant cells. Nature Biotechnology, 21, 1470–1471.
-
Sriraman, R.,
Bardor, M.,
Sack, M., et al.
(2004)
Recombinant anti-hCG antibodies retained in the endoplasmic reticulum of transformed plants lack core-xylose and core-α(13)-fucose residues.
Plant Biotechnology Journal,
2,
279–287.
10.1111/j.1467-7652.2004.00078.x Google Scholar
- Strasser, R., Altmann, F., Mach, L., Glössl, J., Steinkellner, H. (2004) Generation of Arabidopsis thaliana plants with complex N-glycans lacking β1,2-linked xylose and core α1,3-linked fucose. FEBS Letters, 561, 132–136.
- Tekoah, Y., Ko, K., Koprowski, H., et al. (2004) Controlled glycosylation of therapeutic antibodies in plants. Archives of Biochemistry and Biophysics, 426, 266–278.
- Triguero, A., Cabrera, G., Cremata, J., Yuen, C.T., Wheeler, J., Ramirez, N.I. (2005) Plant-derived mouse IgG monoclonal antibody fused to KDEL endoplasmic reticulum-retention signal is N-glycosylated homogeneously throughout the plant with mostly high-mannose-type N-glycans. Plant Biotechnology Journal, 3, 449–457.
- Van Ree, R., Cabanes-Macheteau, M., Akkerdaas, J., et al. (2000) Beta(1,2)-xylose and alpha(1,3)-fucose residues have a strong contribution in IgE binding to plant glycoallergens. Journal of Biological Chemistry, 275, 11451–11458.
- Viëtor, R., Loutelier-Bourhis, C., Fitchette, A.C., et al. (2003) Protein N-glycosylation is similar in the moss Physcomitrella patens and in higher plants. Planta, 203, 269–275.
- Wee, E.Q., Sherrier, D.J., Prime, T.A., Dupree, P. (1998) Targeting of active sialyltransferase to the plant Golgi apparatus. Plant Cell, 10, 1759–1768.
- Wilson, I.B., Altmann, F. (1998) Structural analysis of N-glycans from allergenic grass, ragweed and tree pollens: core alpha1,3-linked fucose and xylose present in all pollens examined. Glycoconjugate Journal, 15, 1055–1070.
- Wright, A., Morrison, S.L. (1998) Effect of C2-associated carbohydrate structure on Ig effector function: studies with chimeric mouse-human IgG1 antibodies in glycosylation mutants of Chinese hamster ovary cells. Journal of Immunology, 160, 393–402.
- York, W.S., Darvill, A.G., McNeil, M., Albersheim, P. (1985) 3-desoxy-D-manno-2-octulosonic acid (KDO) is a component of rhamnogalacturonan II, a pectic polysaccharide in the primary cell walls of plants. Carbohydrate Research, 138, 109–126.
- Zeitlin, L., Olmsted, S.S., Moench, T.C., et al. (1998) A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes. Nature Biotechnology, 16, 1361–1364.
- Zeleny, R., Kolarich, D., Strasser, R., Altmann, F. (2006) Sialic acid concentrations in plants are in the range of inadvertent contamination. Planta, 5, 1–6.
- Zeng, Y., Bannon, G., Thomas Hayden, V., Rice, K., Drake, R., Elbein, A. (1997) Purification and specificity of β1,2-xylosyltransferase, an enzyme that contributes to the allergenicity of some plant proteins. Journal of Biological Chemistry, 272, 31340–31347.
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