Document Detail

N-glycosylation engineering of biopharmaceutical expression systems.
MedLine Citation:
PMID:  19860659     Owner:  NLM     Status:  MEDLINE    
N-glycosylation, the enzymatic coupling of oligosaccharides to specific asparagine residues of nascent polypeptide chains, is one of the most widespread post-translational modifications. Following transfer of an N-glycan precursor in the ER, this structure is further modified by a number of glycosidases and glyco-syltransferases in the ER and the Golgi complex. The processing reactions occurring in the ER are highly conserved between lower and higher eukaryotes. In contrast, the reactions that take place in the Golgi complex are species- and cell type-specific. Due to its non-template driven nature, glycoproteins typically occur as a mixture of glycoforms. Since N-glycans influence circulation half-life, tissue distribution, and biological activity each glycoform has its own pharmacokinetic, pharmacodynamic and efficacy profile. Moreover, modification of glycoproteins with non-human oligosaccharides can result in undesired immunogenicity. Therefore, engineering of the N-glycosylation pathway of most currently used heterologous protein expression systems (bacteria, mammalian cells, insect cells, yeasts and plants) is actively pursued by several academic and industrial laboratories. These research efforts are in the first place directed at humanizing the N-glycosylation pathway and eliminating immunogenic glycotopes. Moreover, one wants to establish new structure-function relationships of different glycoforms, which helps to decreasing the complexity of the N-glycan repertoire towards one defined N-glycan structure. In this review, we discuss the most important recent milestones in the glycoengineering field.
P P Jacobs; N Callewaert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Current molecular medicine     Volume:  9     ISSN:  1875-5666     ISO Abbreviation:  Curr. Mol. Med.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-10-28     Completed Date:  2010-01-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101093076     Medline TA:  Curr Mol Med     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  774-800     Citation Subset:  IM    
Department of Biochemistry, Physiology and Microbiology, Ghent University, Ghent, Belgium.
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MeSH Terms
Bacteria / genetics,  metabolism
Carbohydrate Conformation
Carbohydrate Sequence
Cell Line
Drug Industry*
Glycoproteins* / chemistry,  genetics,  metabolism
Molecular Sequence Data
Oligosaccharides* / chemistry,  metabolism
Plants / genetics,  metabolism
Polysaccharides / chemistry,  metabolism
Protein Engineering / methods*
Protein Isoforms / chemistry,  genetics,  metabolism
Protein Processing, Post-Translational*
Yeasts / genetics,  metabolism
Reg. No./Substance:
0/Glycoproteins; 0/Oligosaccharides; 0/Polysaccharides; 0/Protein Isoforms

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