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Recombinant protein expression systems
As new protein drug candidates steadily increase in number in the post-genomic era,
efficient and economic protein production systems play crucial roles in the evaluation of their efficacy and
commercial potential. MBRI has devoted resources to develop high output protein synthesis for
pre-clinical/clinical studies of protein therapeutics in the pipeline, such as PTH, G-CSF, rhIFN-a,
rhGH and rhLK8. This is achieved by employing a variety of recombinant microbial expression
systems using E. coli, Saccharomyces cerevisiae, Pichia pastoris and Hansenular polymorpha.
 For the
development of an efficient protein production system, our efforts mainly consist of two different approaches;
1) the re-engineering of host strains by investigating the genes involved in protein folding and secretion;
and 2) the process development of fermentation/purification steps.
Currently, our proprietary protein secretion system using S. cerevisiae is being further developed to
improve its genetic stability and protein secretion efficiency. Moreover, the refined system is being applied
to the production of the novel anti-angiogenic protein, rhLK8.
Publications
Lim, H.K., Kim, S.G., Jung, K.H., and Seo, J.H.(2004) Production of the kringle fragments of human
apolipoprotein(a) by continuous lactose induction strategy. J. Biotechnol. 108, 271-278.
[PubMed Citation]
Lim, H.K., Kim, S.G., Jung, K.H., and Seo, J.H.(2004) Statistical selection of amino acids fortifying a minimal
defined medium for a high-level production of the kringle fragments of human apolipoprotein(a). J. Microbiol.
Biotechnol. 14, 90-96.
Lim, H.K., Lee, S.U., Chung, S.I., and Jung, K.H. (2004) Induction of the T7 promoter using lactose for
production of recombinant plasminogen kringle 1-3 in Escherichia coli. J. Microbiol. Biotechnol.
14, 225-230.
Lim, H.K., Choi, S.J., Kim, K.Y., Jung, K.H. (2003) DO-stat controlling two variables for the methanol
induction of rGuamerin in Pichia pastoris and its application to repeated fed-batch. Appl. Microbiol.
Biotechnol. 62, 342-348.
[PubMed Citation]
Kim, K.Y., Lim, H.K., Lee, K.J., Park, D.H., Kang, K.W., Chung, S.I., and Jung, K.H. (2000) Production and
characterization of recombinant Guamerin, an elastase-specific inhibitor, in the methylotrophic yeast Pichia
pastoris. Protein Expr. Purif. 20, 1-9.
[PubMed Citation]
Lim, H.K., Kim, K.Y., Lee, K.J., Park, D.H., Chung, S.I. and Jung, K.H. (2000) Genetic characteristics of
integrated structural gene of rGuamerin in recombinant Pichia pastoris. J. Microbiol. Biotechnol.
10, 470-475.
Lim, H.K., Park, D.H., Chung, S.I., and Jung, K.H. (2000) Production characteristics of interferon-a using an
L-arabinose promoter system in a high-cell-density culture. Appl. Microbiol. Biotechnol. 53, 201-208.
[PubMed Citation]
Lim, H.K. and Jung, K.H. (1998) Improvement of heterologous protein production by controlling postinduction
specific growth rate in recombinant Escherichia coli under control of the PL promoter. Biotechnol.
Prog. 14, 548-553.
[PubMed Citation] |
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