Pharmaceutical Proteins From Methylotrophic Yeasts
Because of their favorable properties, methylotrophic yeasts have become increasingly important as cell factories for the production of biomaterials, therapeutic proteins, and vaccines. As a eukaryote, yeast can perform most of the posttranslational modifications that are required to ensure the functionality and/or stability of recombinant human proteins, such as N- and O-linked glycosylation, phosphorylation, and formation of disulfide bonds. In contrast to other yeast systems, foreign genes can be expressed at high levels under control of strong inducible promoters derived from genes encoding proteins that are involved in methanol metabolism. Furthermore, heterologous proteins can be secreted at high levels into the culture medium, which, in combination with the fact that few endogenous proteins are secreted, significantly facilitates purification of the desired protein. Finally, as unicellular microorganisms, methylotrophic yeasts have major advantages in industrial fermentation.
KeywordsHeterologous Protein Heterologous Gene Methylotrophic Yeast AOX1 Gene Recombinant Human Protein
- 3.Gleeson, M. A. G., White, C. E., Meininger, D. P., and Komives, E. A. (1998) Generation of protease-deficient strains and their use in heterologous protein expression, in Methods in Molecular Biology, vol. 103: Pichia Protocols (Higgins, D. R. and Gregg, J. M., eds.), Humana, Totowa, NJ, pp. 81–94.CrossRefGoogle Scholar
- 5.Kim, M. W., Rhee, S. K., Kim, J. Y., Shimma, Y., Chiba, Y., Jigami, Y., and Kang H. A. (2004) Characterization of N-linked oligosaccharides assembled on secretory recombinant glucose oxidase and cell wall mannoproteins from the methylotrophic yeast Hansenula polymorpha. Glycobiology 14, 243–251.PubMedCrossRefGoogle Scholar
- 15.Pichia Fermentation Process Guidelines, version B, Invitrogen, Carlsbad, CA.Google Scholar