, 50:57 | Cite as

Optimisation of the Cellular Metabolism of Glycosylation for Recombinant Proteins Produced by Mammalian Cell Systems

  • M. ButlerEmail author


Many biopharmaceuticals are now produced as secreted glycoproteins from mammalian cell culture. The glycosylation profile of these proteins is essential to ensure structural stability and biological and clinical activity. However, the ability to control the glycosylation is limited by our understanding of the parameters that affect the heterogeneity of added glycan structures. It is clear that the glycosylation process is affected by a number of factors including the 3-dimensional structure of the protein, the enzyme repertoire of the host cell, the transit time in the Golgi and the availability of intracellular sugar-nucleotide donors. From a process development perspective there are many culture parameters that can be controlled to enable a consistent glycosylation profile to emerge from each batch culture. A further, but more difficult goal is to control the culture conditions to enable the enrichment of specific glycoforms identified with desirable biological activities. The purpose of this paper is to discuss the cellular metabolism associated with protein glycosylation and review the attempts to manipulate, control or engineer this metabolism to allow the expression of human glycosylation profiles in producer lines such as genetically engineered Chinese hamster ovary (CHO) cells.


Antennarity CHO cells Fucosylation Galactosylation Glycoprotein Glycosylation Golgi N-glycan O-glycan Sequon Sialylation 



antibody-mediated cytotoxicity


baby hamster kidney (cells)


core 2 GlcNAC transferase (UDP-GlcNAc: Galβ1,3GalNAc-R β1,6-N-acetyl glucosaminyl transferase)


Chinese hamster ovary (cells)


cytidine monophosphate


dissolved oxygen




endoplasmic reticulum


fucosyl transferase


agalactosylated glycans


monogalactosylated glycans


digalactosylated glycans


N-acetyl galactosamine


GDP mannose 4,6 dehydratase


guanosine diphosphate


glutamine: fructose 6-phosphate amidotransferase


N-acetyl glucosamine


N-acetyl glucosaminyl transferase


human immunodeficiency virus






lysosomal membrane glycoprotein


N-acetyl mannosamine


mouse placental lactogen I


N-acetyl-neuraminic acid


N-glycolyl-neuraminic acid




sialyl transferase


sialyl transferase 3 (CMP-sialic acid: Galβ1,3GalNAc2,3 sialyl transferase)


tissue inhibitors of metalloproteinases


tissue plasminogen activator


uridine diphosphate


uridine triphosphate


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© Springer 2006

Authors and Affiliations

  1. 1.Department of MicrobiologyUniversity of ManitobaWinnipeg, ManitobaCanada

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