Abstract
There is increasing interest in transgenic plant technology for the production of a wide range of recombinant proteins for pharmaceutical and industrial uses. There are many potential benefits in using plants as bioreactors for the production of such economically important proteins, such as the similarities between protein synthesis and post-translational modifications in plant and mammalian cells, the possibility of production scale-up to agricultural levels, as well as a number of safety and ethical issues. A consistent problem however, has been the disappointingly low expression levels achieved in many cases. There are several stages at which intervention might help to improve yield. These include the transformation event, transcription efficiency of the foreign gene, mRNA stability, translation of mRNA to recombinant protein, protein folding and assembly, post-translational modifications, intracellular targeting and transport, protein stability and downstream protein purification. But the fact that some recombinant proteins, particularly complex multimeric immunoglobulins, can be routinely expressed and extracted at levels of around 1% of total soluble protein, suggest that the difficulties with other proteins may lie at the post-translational level.
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References
Borisjuk, N.V., Borisjuk, L.G., Logendra, S., Petersen, F., Gleba, Y., and Raskin, I. (1999). Production of recombinant proteins in plant root exudates. Nature Biotech. 17: 466–469.
Burton, D.R. (1990). Antibody: the flexible adaptor molecule. Trends Biochem. Sci. 15: 64–69.
Carpita, N., Sabularse, D., Montezinos, D., and Delmer, D. P. (1979). Determination of the pore size of cell walls of living plant cells. Science 205: 1144–1147.
De Cosa, B., Moar, W., Lee, S.B., Miller, M., and Daniell, H. (2001). Overexpression of the Bt cry2Aa2 operon in chloroplasts leads to formation of insecticidal crystals. Nature Biotechnol. 19: 71–74.
Denecke, J., Carlsson, L.E., Vidal, S., Hoglund, A.S., Ek, B., van Zetil, M.J., Sinjorgo, K.M., and Palva, E.T. (1995). The tobacco homolog of mammalian calreticulin is present in protein complexes in vivo. Plant Cell 7: 91–406.
Denecke, J., Goldman, MIL, Demolder, J., Seurinck, J., and Botterman, J. (1991). The tobacco luminal binding protein is encoded by a multigene family Plant Cell 3: 1025–1035.
Ellgaard, L., Molinari, M., and Helenius, A. (1999). Setting the standards: quality control in the secretory pathway. Science 286: 1882–1888.
Fiedler, U., and Conrad, U. (1995). High level production and long term storage of engineered antibodies in transgenic tobacco seeds. Bio/Technology 10: 1090–1094.
Firek, S., Draper, J., Owen, M.R., Gandecha, A., Cockburn, B., and Whitelam, G.C. (1993). Secretion of a functional single-chain Fv protein in transgenic tobacco plants and cell suspension cultures. Plant Mol. Biol. 23: 861–870.
Fontes, E.B.P., Shank, B.B., Wrobel, R.L., Moose, S.P., O’Brian, G.R., Wurtzel, E.T., and Boston, R.S. (1991). Characterization of an immunoglobulin binding-protein homolog in the maize floury-2 endosperm mutant. Plant Cell 3: 483–496.
Frigerio, L., Vine, N.D., Pedrazzini, E., Hein, M.B., Wang, F., Ma, J.K., and Vitale, A. (2000). Assembly, secretion, and vacuolar delivery of a hybrid immunoglobulin in plants. Plant Physiol. 123: 1483–1494.
Gething, M.J. (1999). Role and regulation of the ER chaperone BiP. Semin. Cell Dev. Biol. 10: 465–472.
Gleba, D., Borisjuk, N.V., Borisjuk, L.G., Kneer, R., Poulev, A., Skarzhinskaya, M., Dushenkov, S., Logendra, S., Gleba, Y.Y., and Raskin, I. (1999). Use of plant roots for phytoremediation and molecular farming. Proc. Nat. Acad. Sci. USA 96: 5973–5977.
Haas, I.G., and Meo, T. (1988). cDNA cloning of the immunoglobulin heavy chain binding protein. Proc. Nat. Acad. Sci. USA 85: 2250–2254.
Haas, I.G., and Wabl, M. (1983). lmmunoglobulin heavy chain binding protein. Nature 306: 387–389.
Hiatt, A.C., Cafferkey, R., and Bowdish, K. (1989). Production of antibodies in transgenic plants. Nature 342: 76–78.
Knittler, M.R., and Haas, I.G. (1992). Interaction of BiP with newly synthesized immunoglobulin light chain molecules: cycles of sequential binding and release. EMBO J. 11: 1573–1581.
Leborgne-Castel, N., Jelitto-Van Dooren, E.P., Crofts, A.J., and Denecke, J. (1999). Overexpression of BiP in tobacco alleviates endoplasmic reticulum stress. Plant Cell 11: 459–470.
Lesk, A.M., and Chothia, C. (1988). Elbow motion in the immunoglobulins involves a molecular ball-and-socket joint. Nature 335: 188–190.
Ma, J.K.-C., Hiatt, A., Hein, M.B., Vine, N., Wang, F., Stabila, P., van Dolleweerd, C., Mostov, K., and Lehner, T. (1995). Generation and assembly of secretory antibodies in plants. Science 268: 716–719.
Ma, J.K.-C., Lehner, T., Stabila, P., Fux, C.I., and Hiatt, A. (1994). Assembly of monoclonal antibodies with IgG1 and IgA heavy chain domains in transgenic tobacco plants. Eur. J. Immunol. 24: 131–138.
Ma, J.K., Hikmat, B.Y., Wycoff, K., Vine, N.D., Chargelegue, D., Yu, L., Hein, M.B., and Lehner, T. (1998). Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans [see comments]. Nature Medicine 4: 601–606.
Magnuson, N.S., Linzmaier, P.M., Gao, J.W., Reeves, R., An, G., and Lee, J.M. (1996). Enhanced recovery of a secreted mammalian protein from suspension culture of genetically modified tobacco cells. Protein Exp. Purif. 7: 220–228.
Melnick, J., and Argon, Y. (1995). Molecular chaperones and the biosynthesis of antigen receptors. Immunology Today 16: 243–250.
Melnick, J., Dul, J.L., and Argon, Y. (1994). Sequential interaction of the chaperones BiP and GRP94 with immunoglobulin chains in the endoplasmic reticulum. Nature 370: 373–375.
Munro, S., and Pelham, H.R. (1986). An Hsp70-like protein in the ER: identity with the 78 kd glucose-regulated protein and immunoglobulin heavy chain binding protein. Cell 46: 291–300.
Muntz, K. (1998). Deposition of storage proteins. Plant Mol. Biol. 38: 77–99.
Nishikawa, S.I., Fewell, S.W., Kato, Y., Brodsky, J.L., and Endo, T. (2001). Molecular chaperones in the yeast endoplasmic reticulum maintain the solubility of proteins for retrotranslocation and degradation. J Cell Biol. 153: 1061–1070.
Normington, K., Kohno, K., Kozutsumi, Y., Gething, M.J., and Sambrook, J. (1989). S. cerevisiae encodes an essential protein homologous in sequence and function to mammalian BiP. Cell 57: 1223–1236.
Pedrazzini, E., Giovinazzo, G., Bollini, R., Ceriotti, A., and Vitale, A. (1994). Binding of BiP to an assembly-defective protein in plant cells. Plant J. 5: 103–110.
Rose, M.D., Misra, L.M., and Vogel, J.P. (1989). KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78 gene. Cell 57: 1211–1221.
Roth, R.A., and Pierce, S.B. (1987). In vivo cross-linking of protein disulfide isomerase to immunoglobulins. Biochemistry 26: 4179–4182.
Shorrosh, B.S., and Dixon, R.A. (1991). Molecular cloning of a putative plant endomembrane protein resembling vertebrate protein disulfide-isomerase and a phosphatidylinositol-specific phospholipase C. Proc. Nat. Acad. Sci. USA 88: 10941–10945.
Shusta, E.V., Raines, R.T., Pluckthun, A., and Wittrup, K.D. (1998). Increasing the secretory capacity of Saccharomyces cerevisiae for production of single-chain antibody fragments. Nature Biotech. 16: 773–777.
Tavladoraki, P., Benvenuto, E., Trinca, S., De Martinis, D., Cattaneo, A., and Galeffi, P. (1993). Transgenic plants expressing a functional single-chain Fv antibody are specifically protected from virus attack. Nature 366: 469–472.
Ting, J., Wooden, S.K., Kriz, R., Kelleher, K., Kaufman, R.J., and Lee, A.S. (1987). The nucleotide sequence encoding the hamster 78-kDa glucose-regulated protein (GRP78) and its conservation between hamster and rat. Gene 55: 147–152.
Vanhove, M., Usherwood, Y.K., and Hendershot, L.M. (2001). Unassembled lg heavy chains do not cycle from BiP in vivo but require light chains to trigger their release. Immunity 15: 105–114.
Vine, N.D., Drake, P., Hiatt, A., and Ma, J.K. (2001). Assembly and plasma membrane targeting of recombinant immunoglobulin chains in plants with a murine immunoglobulin transmembrane sequence. Plant Mol. Biol. 45: 159–167.
Vitale, A., and Denecke, J. (1999). The endoplasmic reticulum-gateway of the secretory pathway. Plant Cell 11: 615–628.
Vitale, A., and Galili, G. (2001). The endomembrane system and the problem of protein sorting. Plant Physiol. 125: 115–118.
Wongsamuth, R., and Doran, P.M. (1997). Production of monoclonal antibodies by tobacco hairy roots. Biotechnology and Bioengineering 54: 401–415.
Wooden, S.K., Kapur, R.P., and Lee, A.S. (1988). The organization of the rat GRP78 gene and A23187-induced expression of fusion gene products targeted intracellularly. Exp. Cell Res. 178: 84–92.
Yamawaki-Kataoka, Y., Nakai, S., Miyata, T., and Honjo, T. (1982). Nucleotide sequences of gene segments encoding membrane domains of immunoglobulin gamma chains. Proc. Nat. Acad. Sci. USA 79: 2623–2627.
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Drake, P.M.W., Chargelegue, D.M., Obregon, P., Prada, A., Frigerio, L., Ma, J. (2003). The Assembly and Potential Applications of Immunoglobulins Expressed in Transgenic Plants. In: Vasil, I.K. (eds) Plant Biotechnology 2002 and Beyond. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-2679-5_75
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DOI: https://doi.org/10.1007/978-94-017-2679-5_75
Publisher Name: Springer, Dordrecht
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