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Recent Advances in the Production of Mammalian-Type Sugar Chains in Yeast

  • Yasunori Chiba
  • Yoshifumi Jigami

Abstract

Protein therapeutics, such as enzyme replacement therapy, antibody therapeutics, and cytokine administration, are now known as the largest class of new candidates developed by the pharmaceutical companies. Yeasts have been used to produce industrial enzymes and are often chosen as the expression system because manufacturing costs are of primary concern. However, yeasts have a drawback of inability to attach mammalian-type sugar chain for the production of therapeutic glycoproteins for human use. N-glycosylated sugar chain in yeast is a mannan-type, which is partly antigenic in human and is sometimes trapped and cleared by mannose-specific receptors or lectins. Over the past 15 years or so, several approaches have been attempted to substitute yeast glycosylation pathway for a human one, and recently, many advances in the expression of therapeutic glycoproteins with mammalian-type sugar chains in yeast have been demonstrated.

Keywords

Enzyme Replacement Therapy Fabry Disease Sugar Chain Mannose Residue Epidermal Growth Factor Domain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Amano K, Chiba Y, Kasahara Y, Kato Y, Kaneko M-K, Kuno A, Ito H, Kobayashi K, Hirabayashi J, Jigami Y, Narimatsu H (2008) Engineering of mucin-type human glycoprotein in yeast cells. Proc Nat Acad Sci USA 105:3232–3237PubMedCrossRefGoogle Scholar
  2. Chiba Y, Suzuki M, Yoshida S, Yoshida A, Ikenaga H, Takeuchi M, Jigami Y, Ichishima E (1998) Production of human compatible high mannose-type (Man5GlcNAc2) sugar chains in Saccharomyces cerevisiae. J Biol Chem 273:26298–26304PubMedCrossRefGoogle Scholar
  3. Chiba Y, Sakuraba H, Kotani M, Kase R, Kobayashi K, Takeuchi M, Ogasawara S, Maruyama Y, Nakajima T, Takaoka Y, Jigami Y (2003) Production in yeast of alpha-galactosidase A, a lysosomal enzyme applicable to enzyme replacement therapy for Fabry disease. Glycobiology 12:821–828CrossRefGoogle Scholar
  4. Chigira Y, Oka T, Okajima T, Jigami Y (2008) Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisise: production of O-fucosylated epidermal growth factor domains Glycobiology, in press, doi:10.1093/glycob/cwn008Google Scholar
  5. Hamilton SR, Bobrowicz P, Bobrowicz B, Davidson RC, Li H, Mitchell T, Nett JH, Rausch S, Stadheim TA, Wischnewski H, Wildt S, Gerngross TU (2003) Production of complex human glycoproteins in yeast. Science 301:1244–1246PubMedCrossRefGoogle Scholar
  6. Hamilton SR, Davidson RC, Sethuraman N, Nett JH, Jiang Y, Rios S, Bobrowicz P, Stadheim TA, Li H, Choi BK, Hopkins D, Wischnewski H, Roser J, Mitchell T, Strawbridge RR, Hoopes J, Wildt S, Gerngross TU (2006) Humanization of yeast to produce complex terminally sialylated glycoproteins. Science 313:1441–1443PubMedCrossRefGoogle Scholar
  7. Nakayama K, Nagasu T, Shimma Y, Kuromitsu J, Jigami Y (1992) OCH1 encodes a novel membrane bound mannosyltransferase: outer chain elongation of asparagine-linked oligosaccharides. EMBO J 11:2511–2519PubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Yasunori Chiba
    • 1
    • 2
  • Yoshifumi Jigami
    • 1
  1. 1.Research Institute for Cell EngineeringNational Institute of Advanced Industrial Science and TechnologyTsukubaJapan
  2. 2.Research Center for Medical GlycoscienceNational Institute of Advanced Industrial Science and TechnologyTsukubaJapan

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