Heterologous Glycoprotein Production (Yeast)

  • Yasunori ChibaEmail author
Reference work entry


Biologics has attracted a great deal of attention, and antibodies, enzymes, cytokines, and vaccines for therapeutic uses are being developed. These proteins are mostly glycosylated and therefore are produced in mammalian cells. From the viewpoint of cost reduction and risk management of viral infection spreading through the use of contaminated protein therapeutics, the development of alternative glycoprotein expression system has been promoted, and consequently, protein expression systems in yeast have been expected. Yeast cells cannot generate human-type glycans, and the different glycan structures on the therapeutic glycoproteins produced in yeast may cause immunological incompatibility with human. Glycan remodeling of yeast cells has been one of the issues in order to produce heterologous glycoprotein, and recent advances in the field of yeast glycobiology and synthetic biology have shown significant promise. In this chapter, several significant developments in this field are reviewed.


Yeast Glycoprotein Glycan remodeling N-glycan Mannose-6-phosphate O-glycan 


  1. Amano K, Chiba Y, Kasahara Y et al (2008) Engineering of mucin-type human glycoproteins in yeast cells. Proc Natl Acad Sci U S A 105:3232–3237CrossRefPubMedPubMedCentralGoogle Scholar
  2. Chiba Y, Suzuki M, Yoshida S et al (1998) Production of human compatible high mannose-type (Man5GlcNAc2) sugar chains in Saccharomyces cerevisiae. J Biol Chem 273:26298–26304CrossRefPubMedGoogle Scholar
  3. Chiba Y, Sakuraba H, Kotani M et al (2002) Production in yeast of alpha-galactosidase A, a lysosomal enzyme applicable to enzyme replacement therapy for Fabry disease. Glycobiology 12:821–828CrossRefPubMedGoogle Scholar
  4. Choi BK, Bobrowicz P, Davidson RC et al (2003) Use of combinatorial genetic libraries to humanize N-linked glycosylation in the yeast Pichia pastoris. Proc Natl Acad Sci U S A 100:5022–5027CrossRefPubMedPubMedCentralGoogle Scholar
  5. Hamilton SR, Davidson RC, Sethuraman N et al (2006) Humanization of yeast to produce complex terminally sialylated glycoproteins. Science 313:1441–1443CrossRefPubMedGoogle Scholar
  6. Hamilton SR, Cook WJ, Gomathinayagam S et al (2013) Production of sialylated O-linked glycans in Pichia pastoris. Glycobiology 23:1192–1203CrossRefPubMedGoogle Scholar
  7. Nakayama K, Nagasu T, Shimma Y et al (1992) OCH1 encodes a novel membrane bound mannosyltransferase: outer chain elongation of asparagine-linked oligosaccharides. EMBO J 11:2511–2519PubMedPubMedCentralGoogle Scholar
  8. Tiels P, Baranova E, Piens K et al (2012) A bacterial glycosidase enables mannose-6-phosphate modification and improved cellular uptake of yeast-produced recombinant human lysosomal enzymes. Nat Biotechnol 30:1225–1231CrossRefPubMedGoogle Scholar
  9. Tsuji D, Akeboshi H, Matsuoka K et al (2011) Highly phosphomannosylated enzyme replacement therapy for GM2 gangliosidosis. Ann Neurol 69:691–701CrossRefPubMedGoogle Scholar
  10. Vervecken W, Callewaert N, Kaigorodov V et al (2007) Modification of the N-glycosylation pathway to produce homogeneous, human-like glycans using GlycoSwitch plasmids. Methods Mol Biol 389:119–138CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan 2015

Authors and Affiliations

  1. 1.Glycomedicine Technology Research CenterNational Institute of Advanced Industrial Science and Technology (AIST)TsukubaJapan

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