Adi Santoso
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Glycobiology is a study of the structure, biosynthesis, glycosylation and biology of glycans that are widespread in nature. Through the process of glycosylation which is one of the most post-translational forms of protein modification, macromolecular structures that are as diverse as glycoproteins can be formed. In other words, glycosylation is one of the most common structural modifications used by biological systems to expand proteomic diversity. This makes glycosylation a very high prevalence, estimated at 50-70% of all proteins are glycoproteins. Glycosylation can affect proteolysis patterns, ligand-receptor interactions, oncogenic signal transduction, body immunity, cell adhesion and cell matrix. Because of the high level of structural variability that arises from the glycosylation process, many new strategies can be made using the uniqueness of this glycoprotein modification, especially in the pharmaceutical field. This includes modifications in protein engineering in the expression systems of yeast, plant cells and mammalian cells.



glycobiology, glycans, glycosylation, therapeutic proteins.

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Adamczyk, B., Tharmalingam, T. and Rudd, P.M., 2012. Glycans as cancer biomarkers.Biochim. Biophys. Acta, 1820, pp. 1347–1353.

Aebi, M., 2013. N-linked protein glycosylation in the ER. Biochim. Biophys. Acta. 1833, pp. 2430–2437.

Animal Cell Biology, accessed 3 August 2011. ( /2011/08/03/chapter-3-bio-membrane-and-cell-surface-membrane-carbohydrates/).

Anne, D., Alaa, G., Federico, S., and Paul, H., 2010. Similarities and Differences in the GlycosylationMechanisms in Prokaryotes and Eukaryotes. International Journal of Microbiology. Article ID 148178, 14 pages. doi:10.1155/2010/148178

Bieberich, E., 2014. Synthesis, processing, and function of N-glycans in N-glycoproteins. Adv. Neurobiol, 9, pp. 47–70.

Butler, M., 2006. Optimisation of the cellular metabolism of glycosylation for recombinant proteins produced by mammalian cell systems. Cytotechnology, 50, pp. 57-76.

Chung, C.H., Mirakhur, B., Chan, E., Le, Q.T, Berlin, J., Morse, M., Murphy, B.A., Satinover, S.M., Hosen, J., and Mauro, D., 2008. Cetuximabinduced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N. Engl. J. Med, 358, pp. 1109-1117.

Colin, R., Tyler, J.S, 2019. Matthew B. Renfrow and Jan Novak. Glycosylation in health and disease. Nature Review, 15, pp. 346-366.

Cotton, S., Azevedo, R., Gaiteiro, C., Ferreira, D., Lima, L., Peixoto A., 2017. Targeted O-glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced-stage bladder tumours. Mol. Oncol, 11, pp. 895–912.

Dalit, S.B. and Yaakov, L., 2008. Effect of glycosylation on protein folding: A close look at thermodynamic stabilization. PNAS, 105(24), pp. 8256-8261.

Dwek, R.A. 1996. Glycobiology: Toward Understanding the Function of Sugars. Chem. Rev, 96 (2), pp. 683–720.

Drickamer K, Taylor ME (2006). Introduction to Glycobiology (2nd ed.). Oxford University Press, USA. ISBN 978-0-19-928278-4.

Egrie, J.C. and Browne, J.K., 2001. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br. J. Cancer, 84, pp. 3–10.

Elliott, S., Lorenzini, T. and Asher, S., 2013. Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat. Biotechnol, 21, pp. 414–21.

Ferreira, I. G. et al. 2018. Glycosylation as a main regulator of growth and death factor receptors signaling. Int. J.Mol. Sci. 19, E580.

Fuster, M.M. and Esko, J.D., 2005. The sweet and sour of cancer: glycans as novel therapeutic targets. Nat. Rev. Cancer, 5, pp. 526–542.

Gagneux, P. and Varki, A., 1999. Evolutionary considerations in relating oligosaccharide diversity to biological function. Glycobiology, 9, pp. 747–755.

Gerngross, T.U. 2004. Advances in the production of human therapeutic proteins in yeasts and filamentous fungi. Nat. Biotechnol, 22, pp. 1409-1414.

Hakomori, S. and Kannagi, R., 1983. Glycosphingolipids as tumor-associated and differentiation markers. J. Natl. Cancer Inst. 71, pp. 231–251.

Haltiwanger, R.S. and Lowe, J.B., 2004. Role of glycosylation in development. Annu. Rev. Biochem. 73, pp. 491–537.

Hamilton, S.R., Davidson, R.C., Sethuraman, N., Nett, J.H., Youwei, J.Y., Rios, S., Bobrowicz, P., Stadheim, T.A., Li, H., Choi, B.K., Hopkins, D., Wischnewski, H., Roser, J., Mitchell, T., Strawbridge, R.R., Hoopes, J., Wildt, S. and Gerngross, T.U., 2006. Humanization of yeast to produce complex humanization of yeast to produce complex terminally sialylated glycoproteins. Science, 313, pp. 1441-1443.

Hamilton, S.R. and Gerngross, T.U., 2007. Glycosylation engineering in yeast: the advent of fully humanized yeast. Curr. Opin. Biotechnol. 18, pp. 387–392.

Häuselmann, I. and Borsig, L., 2014. Altered tumor-cell glycosylation promotes metastasis. Front Oncol, 4, 28.

Helenius, A. and Aebi, M. 2001. Intracellular functions of N-glycans. Science, 291, pp. 2364-2369.

Hossler, P. Khattak, S.F. and Li, Z.J., 2009. Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology, 19, pp. 936-949.

Huijuan, L. and Marc d’Anjou., 2009. Pharmacological significance of glycosylation in therapeutic proteins. Curr. Opinion in Biotech, 20(6), pp. 678–684.

Jayapal, K.P., Wlaschin, K.F., Hu, W.S. and Yap M.G., 2007. Recombinant protein therapeutics from CHO cells-20 years and counting. Chemical Engineering Progress, 103, pp. 40–47.

Jonathan, S., 2015. Bacterial modulation of host glycosylation - in infection, biotechnology, and therapy. Dissertation. Lund University, Sweden.

Kannagi, R., Yin, J., Miyazaki, K. and Izawa, M., 2008. Current relevance of incomplete synthesis and neo-synthesis for cancer-associated alteration of carbohydrate determinants–Hakomori’s concepts revisited. Biochim Biophys Acta. 1780, pp. 525–531.

Kazuaki Ohtsubo and Jamey, D.M., 2006. Glycosylation in Cellular Mechanisms of Health and Disease. Cell, 126, pp. 855-867.

Kornfeld, S. and Kornfeld, R., 1985. Assembly of asparagine-linked oligosaccharides. Annu. Rev. Biochem. 54, pp. 631–644.

Larissa, K. and Chi, H.Wong., 2016. Understanding the Chemistry and Biology of Glycosylation with Glycan Synthesis. Annu. Rev. Biochem, pp. 85: 599–630

Martina, D. and Richard, S., 2015. Using glyco-engineering to produce therapeutic proteins. Expert Opin Biol Ther, 15(10), pp. 1501–1516.

Mescher, L. and Strominger, J.L., 1976. Purification and characterization of a prokaryotic glycoprotein from the cell envelope of Halobacterium salinarium. Journal of Biological Chemistry, 251(7), pp. 2005–2014.

Moremen, K.W., Tiemeyer, M. and Nairn, A.V., 2012. Vertebrate protein glycosylation: diversity, synthesis and function. Nat. Rev. Mol. Cell Biol, 13, pp. 448–462.

Nathan, S., 1986. Biochemical Nomenclature (JCBN) Nomenclature of glycoproteins, glycopeptides and peptidoglycans Recommendations. Eur. J. Biochem., 159, pp. 1-6.

Ono, M. and Hakomori, S., 2004. Glycosylation defining cancer cell motility and invasiveness. Glycoconj J, 20, pp. 71–78.

Peixoto, A., Fernandes, E., Gaiteiro, C., Lima, L., Azevedo, R., Soares, J., 2016. Hypoxia enhances the malignant nature of bladder cancer cells and concomitantly antagonizes protein O-glycosylation extension. Oncotarget, 7, pp. 63138–63157.

Pinho, S.S. and Reis, C.A., 2015. Glycosylation in cancer: mechanisms and clinical implications. Nat. Rev. Cancer, 15, pp. 540–555.

Ricardo, J.S. dan Griebenow, K., 2009. Effects of Glycosylation on the Stability of Protein Pharmaceuticals. J Pharm Sci, 98(4), pp. 1223–1245.

Rudd, P., Elliott, T., Cresswell, P., Wilson, I. and Dwek, R., 2001. Glycosylation and the immune system. Science, 291, 8.

Santoso, A.,a Wisnuwardhani, P.H., Kusumawati, A., Rubiyana, Y, Septisetyani, E.P. and and Nurainy, N. 2019. Improvement of mammalian cells performance by addition of glucose for the expression of erythropoietin with 2 additional link in CHO-DG44 cells. IOP Conf. Series: Earth and Environmental Science 439. doi:10.1088/1755-1315/439/1/012057.

Santoso, A.,b Wisnuwardhani, P.H., Kusumawati, A., Herawati, N., Rubiyana, Y., Septisetyani, E.P. and Nurainy, N. 2019. Methotrexate gene amplification for development of erythropoietin with 2 additional N-link producing cell lines. IOP Conf. Series: Earth and Environmental Science 439. doi:10.1088/1755-1315/439/1/012006.

Sarrazin, S., Lamanna, W.C. and Esko, J.D. 2011. Heparan sulfate proteoglycans. Cold Spring Harb Perspect Biol 3: a004952.

Sharon, Y. and Vered, P.K., 2020. Glycosylated Biotherapeutics: Immunological Effects of N-Glycolylneuraminic Acid. Vol. 11. Article 21.

Shrimal, S. and Gilmore, R., 2013. Glycosylation of closely spaced acceptor sites in human glycoproteins. J. Cell Sci. 126, pp. 5513–5523.

Sinclair, A.M. and Elliott, S., 2005, Glycoengineering: the effect of glycosylation on the properties of therapeutic proteins. J Pharm Sci. 94, pp. 1626-1635.

Song, R., Oren, D.A., and Franco, D., 2013 Strategic addition of an N-linked glycan to a monoclonal antibody improves its HIV-1-neutralizing activity. Nat. Biotechnol. 31, pp. 1047–52.

Stowell, S.R. and Ju T,C., Protein glycosylation in cancer. Annu Rev Pathol. (2015) 10:473–510.

Szymanski, C.M and Wren, B.W., 2005. Protein glycosylation in bacterial mucosal pathogens. Nature Reviews Microbiology, 3(3), pp. 225–237.

Varki, A. 2011, Evolutionary forces shaping the Golgi glycosylation machinery: Why cell surface glycans are universal to living cells. Cold Spring Harb Perspect Biol 3: a005462.

Varki, A., 2017. Biological roles glycans. Glycobiology. 27 (1), pp. 3–49.

Varki, A., Cummings, R., Esko, J., Freeze, H. and Hart, G. (1998). Essentials of glycobiology (Cold Spring Harbor Laboratories Press).

Wacker, M., Linton, D. and Hitchen, P.G., 2002. N-linked glycosylation in Campylobacter jejuni and its functional transfer into E. coli, Science, 298(5599), pp. 1790–1793.

Young, N.M, Brisson, J.R., Kelly J, 2002, Structure of the N-linked glycan present on multiple glycoproteins in the gram-negative bacterium, Campylobacter jejuni,” 2002. Journal of Biological Chemistry. 277 (45), pp. 42530–42539

Zielinska, D.F., Gnad F, Schropp KI. 2012. Mapping N-glycosylation sites across seven evolutionarily distant species reveals a divergent substrate proteome despite a common core machinery. Mol Cell. 46, pp. 542–8.


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