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Biotechnology Process Engineering Center

Biotechnology Process Engineering Center
Objectives
Our goal is to develop industrial platform technology for biological products. In particular, we intensively carry out a process scale-up towards the optimization and commercialization for the production of biomaterials and biopharmaceuticals using pilot-plant facilities in order to expand research outcomes and to stimulate commercialization. Additionally, we systematically support the business activities of the bioindustry and cultivate human resources through academic-industrial collaborations.
Researchers
researcher name and research fields
Name Research Fields
Eun-Gyo Lee
(Associate Director)
  • Biochemical engineering
  • Biologics manufacturing
  • Animal cell culture/Separation and purification
Jung-Oh Ahn
  • Biochemical engineering
  • Molecular breeding of yeast and bacterial cells
Eui-Sung Choi
  • Metabolic engineering
  • Enzyme engineering
  • Yeast biotechnology
Hong-Weon Lee
  • Fermentation physiology and Microbial engineering
  • Bioprocess engineering
Woo Young Jeon
  • Microbial metabolic engineering
Chun-Suk Kim
  • Management of biological pilot plant operations and equipment
Hyeok-Won Lee
  • Support for pilot-scale upstream equipment
Jin Gyeom Lee
  • Support for pilot-scale downstream equipment
Won Kyo Kim
  • Support for pilot-scale upstream equipment
Kyoung-hwa Ryu
  • Support for biological pilot-scale downstream equipment
research areas
  • Microbial fermentation and scale-up research
    • Development of novel expression system for recombinant proteins
    • Development of industrial strain
    • Process development
    • Scale-up research for the production
  • Animal cell culture for biologics production
    • Screening of stable cell line producing therapeutic antibody
    • High-cell density culture of mammalian cells
    • Process design for quality control
  • Separation and purification technology
    • Optimization of chromatography and membrane processes
    • Protein/Organic acid purification
    • Scale-up in separation and purification process
Achievements
  • Development of biological process for the production of microbial metabolites
    • Pilot-scale processes for the production of microbial metabolites such as amino acids (ornithine, threonine, and proline), antibiotics, and shikimic acid have been pioneered. This technology includes not only process development but also strain development by traditional mutagenesis and genetic engineering.
  • Over-expression and purification of recombinant proteins
    • WHere technology for the production of heterologous proteins of interest in both E. coli and P. pastoris have been developed. It involves over-expression of a target protein, fusion tag selection, cleavage optimization, and serial chromatographic purification, which can be applied for manufacturing therapeutic proteins and functional enzymes.
  • Development of a novel Pichia expression system
    • Two strong methanol-free promoters in P. pastoris: translation elongation factor 1a promoter (PTEF1) with high growth-associated expression characteristics and phosphate-responsive promoter (PPHO89) of a sodium phosphate symporter were developed. Also, a cost-effective and simple PTEF1- and PPHO89-based fermentation process was developed for industrial applications. Furthermore, we established an easy-to-use multicopy system in P. pastoris using autonomous replication sequences (ARS) and an episomal plasmid to maintain multiple genes of interest in P. pastoris and enhance heterologous expression compared with a single copy integration in P. pastoris.
  • Developement of in silico constraints-based flux analysis tool based on the cofactor regeneration view
    • We established an integrated system for the expression of Apx toxins, which are essential proteins for protection against A. pleuropneumoniae infection, as subunit antigens against porcine pleuropneumonia that makes it possible to obtain soluble and biologically active Apx toxins in E. coli without additional refolding steps. Additionally, the products from the developed expression vectors elicit immunological responses and protective immunity aginst A. pleuropneumoniae infection in an infected guinea pig model.
  • Production of therapeutic proteins in mammalian cell culture
    • Mammalian cell culture has become the dominant system for the production of recombinant proteins for clinical applications because of their proper protein folding and complete post-translational modification. We are currently developing rCHO cell culture technology for the manufacture of therapeutic proteins in a suspension bioreactor. Additionally, we are improving upon avaliable boosting technology for high-quality proteins by genetically engineered cells. Furthermore, we have developed chromatographic purification technologies and high-throughput precision analysis.