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After the transport of the glycoprotein to the cis-Golgi, the pathway of N-glycosylation bifurcates. Some N-glycans can be moved to subsequent steps of the secretory pathway without further modifications, or alternatively, with the removal of a few mannoses (Oligo Mannoses pathway). In yeast and other unicellular species, a series of mannose residues are added (High Mannoses pathway). The presence of this modification is a major obstacle to the production of pharmaceutical drugs in yeast, where the HighMannose pathway must be inhibited or modified in order to avoid the presence of high mannose xenoglycans.<br>The first N-glycan modification step is the trimming of up to four mannoses by one of three mannosidase enzymes. Moreover, Glycoproteins that have not entered in the Calnexin/Calreticulin cycle or that have not had their glucose residues trimmed earlier in the ER, can enter the main pathway here due to the existence to an alternative route catalyzed by the enzyme Endomannosidase I (Schachter, 2000; Stanley et al, 2009)<br>
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