Yeasts are attractive hosts for production of mammalian proteins requiring posttranslational processing, because yeasts offer advantages of both eukaryotic expression mechanisms and bacteria-like growth and handling. Thus for the past 22 years yeasts have been used to overcome the shortcomings of bacterial expression systems. As in Escherichia coli yeasts can provide intracellular as well as secreted expression. By applying short signaling sequences, the expressed proteins can be directed to extracellular secretion or to distinct compartments of the cell (1). Because Saccharomyces cerevisiae tends to hyperglycosylate secreted proteins, this strain is primarily used for intracellular production. Other yeast strains (i.e., Pichia pastoris, Hansenula polymorpha, Schizosaccharomyces pompe, Klyveromyces lactis, or Yarrowia lipolytica) are more suited for secretion (2). Among the best-developed systems for large-scale protein production is P. pastoris-based expression. A notable advantage of Pichia pastoris compared with S. cerevisiae is that Pichia pastoris may produce levels 10-100-fold higher of heterologous protein (3-5) and that Pichia pastoris does not hyperglycosylate as S. cerevisiae does upon secretion. Both yeasts have a majority of N-linked glycosylation of the high-mannose type, but in Pichia the average length of the oligosaccharide chain is 8-14 mannose residues per side chain, whereas in Saccharomyces it is between 50-150 mannoses (6). In addition, S. cerevisiae core oligosaccharides have terminal alpha1,3 glycan linkages, and P. pastoris has none. The alpha1,3 glycan linkage is believed to be responsible for the antigenic nature of proteins produced by secretion from S. cerevisiae.FAU - Nohr, Jan.

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Journal Article | Research Support, Non-U.S. Gov't

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Nøhr J, Kristiansen K, Krogsdam AM

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