Re-engineered Yeast Glycosylation System Might Replace Mammalian Cell Expression

Lebanon, NH (Sept. 7)-Scientists from GlycoFi, Inc. (www.glycofi.com), a wholly owned subsidiary of Merck & Co. (Whitehouse Station, NJ, www.merck.com), in collaboration with Dartmouth-Hitchcock Medical Center, have engineered yeast cells capable of producing a broad range of recombinant therapeutic proteins with fully human sugar structures (glycosylation). Until now, these sugar structures, which ensure a glycoprotein’s biological activity and half-life, required the expression of therapeutic glycoproteins from mammalian host cells.

As reported in the Sept. 8, 2006, issue of Science, the research team genetically engineered the Pichia pastoris yeast to secrete human glycoproteins with fully complex, terminally sialyated N-glycans. Recombinant erythropoietin, which stimulates the production of red blood cells, was successfully expressed using these yeast strains, purified, and its activity demonstrated in vivo.

According to GlycoFi, the work “has the potential to eliminate the need for mammalian cell culture, while improving control over glycosylation and improving performance characteristics of many therapeutic proteins.” The achievement follows a six-year study involving not only the elimination of yeast-specific glycosylation reactions but also the introduction of 14 heterologous genes.