Productivity Improvement of a Recombinant Fermentation through Decrease of Growth Rate Differentials

다국어 초록 (Multilingual Abstract)

The growth rate differential caused by the overexpression of a cloned gene accelerates takeover of bioreactor by plasmid-free cell population and results in productivity decrease. In an attempt to improve productivity of a recombinant fermentation by decreasing growth rate differentials, the par locus from pSC101 was inserted into a multicopy plasmid, pPLc-RP 4.5, giving rise to pPLP that is the same plasmid as pPLc-RP4.5 except for the presence of the par locus. It was found that pPLP content in the pPLP-bearing strain was decreased by a about 30% as compared to that in the pPLc-RP4.5-bearing strain although the presence of the par locus significantly increased plasmid stability. To see the effects of the par locus on specific growth rates, specific growth rates of the pPLc-RP4.5-bearing strain, pPLP-bearing strain and host strain were measured using a two-stage contiunous culture system. It was observed that the specific growth rates of the pPLc-RP4.5-bearing strain were lower than those of the host strain but the specific growth rates of the pPLP-bearing strain were similar to those of the host strain at the same growth conditions. These results suggest that the par locus decreased the growth rate differentials caused by the overproduction of β-galactosidase in the pPLP-bearing strain. In batch cultures, even though the pPLP-bearing strain and the pPLc-RP4.5-bearing strain gave similar specific productivities, the pPLP-bearing strain showed a significant increase in cell density as compared to the pPLc-RP4.5-bearing strain. As a result, the pPLP-bearing cells produced more β-galactosidase per volume per time than the pPLc-RP4.5-bearing cells.