Applied Microbiology and Biotechnology

, Volume 86, Issue 4, pp 1135–1143

Overexpression of protein disulfide isomerases enhances secretion of recombinant human transferrin in Schizosaccharomyces pombe

Applied Genetics and Molecular Biotechnology

DOI: 10.1007/s00253-009-2393-x

Cite this article as:
Mukaiyama, H., Tohda, H. & Takegawa, K. Appl Microbiol Biotechnol (2010) 86: 1135. doi:10.1007/s00253-009-2393-x


Although the fission yeast Schizosaccharomyces pombe has been used for high-level heterologous protein production, the productivity of secreted human serum transferrin (hTF) has been low, presumably, because the protein harbors twenty disulfide bonds and two N-glycosylation sites. In the present study, we found that overexpression of endogenous putative protein disulfide isomerase (PDI) improved productivity. Whole genome sequence analysis of S. pombe revealed five putative PDI genes and overexpression of two of them, SPAC17H9.14c and SPBC3D6.13c (SpPdi2p or SpPdi3p, respectively), significantly improved the productivity of secreted hTF. GFP-fused SpPdi2p and SpPdi3p were found to localize to the endoplasmic reticulum. Co-overexpression of SpPdi2p or SpPdi3p with hTF coupled with modifications to the growth medium reported in our previous study were able to increase the level of secreted hTF approximately 30-fold relative to conventional conditions.


Protein disulfide isomerase Schizosaccharomyces pombe Heterologous protein production Human transferrin 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Hiroyuki Mukaiyama
    • 1
    • 2
  • Hideki Tohda
    • 1
  • Kaoru Takegawa
    • 2
  1. 1.ASPEX Division, Research CenterAsahi Glass Co., Ltd.YokohamaJapan
  2. 2.Laboratory of Applied Microbiology, Department of Bioscience and Biotechnology, Faculty of AgricultureKyushu UniversityFukuokaJapan

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