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Enhanced Production of Human Serum Albumin by Fed-Batch Culture of Hansenula polymorpha with High-Purity Oxygen

  • Youn, Jong-Kyu (Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology) ;
  • Shang, Longan (Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology) ;
  • Kim, Moon-Il (Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology) ;
  • Jeong, Chang-Moon (Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology) ;
  • Chang, Ho-Nam (Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology) ;
  • Hahm, Moon-Sun (Molecular Biology and Protein Engineering Laboratory, Bioprogen Co., Ltd., Daedeok BioCommunity) ;
  • Rhee, Sang-Ki (Korea Research Institute of Bioscience and Biotechnology) ;
  • Kang, Hyun-Ah (Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2009.09.30
  • Accepted : 2010.08.12
  • Published : 2010.11.28

Abstract

Fed-batch cultures of Hansenula polymorpha were studied to develop an efficient biosystem to produce recombinant human serum albumin (HSA). To comply with this purpose, we used a high-purity oxygen-supplying strategy to increase the viable cell density in a bioreactor and enhance the production of target protein. A mutant strain, H. polymorpha GOT7, was utilized in this study as a host strain in both 5-l and 30-l scale fermentors. To supply high-purity oxygen into a bioreactor, nearly 100% high-purity oxygen from a commercial bomb or higher than 93% oxygen available in situ from a pressure swing adsorption (PSA) oxygen generator was employed. Under the optimal fermentation of H. polymorpha with highpurity oxygen, the final cell densities and produced HSA concentrations were 24.6 g/l and 5.1 g/l in the 5-l fermentor, and 24.8 g/l and 4.5 g/l in the 30-l fermentor, respectively. These were about 2-10 times higher than those obtained in air-based fed-batch fermentations. The discrepancies between the 5-l and 30-l fermentors with air supply were presumably due to the higher contribution of surface aeration over submerged aeration in the 5-l fermentor. This study, therefore, proved the positive effect of high-purity oxygen in enhancing viable cell density as well as target recombinant protein production in microbial fermentations.

Keywords

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