Glycosylation engineering in yeast: the advent of fully humanized yeast

Yeasts have been extensively used as model organisms to elucidate cellular processes and their mechanism in lower eukaryotes. Consequently, a large number of powerful genetic tools have been developed to engineer yeast and improve its utility. These tools and the development of efficient large-scale fermentation processes have made recombinant protein expression in yeast an attractive choice. However, for the production of glycoproteins for human use, native high-mannose yeast glycosylation is not suitable and therefore represents a major limitation for yeast based protein expression systems. Over the last two decades several groups have attempted to overcome this problem, yet with limited success. Recently however, major advances in the glycoengineering of the yeast Pichia pastoris, have culminated in the production of fully humanized sialylated glycoproteins.