This study was carried out for the high density cultivation of r-DNA E. coli cells harboring trp plasmid gene in fed-batch and cell filtration recycle system.
In batch and fed-batch mode, the cell mass density of 5-10 g/l was obtained and the cells did not grow above it. This may be caused by the inhibitory metabolites produced by the cells. Among those the acetic acid was considered as the most inhibitory material in cell growth.
To reduce the inhibitory effect of those toxic materials, the cell filtration recycle system using the hollow fiber membrane module was used. In this mode the cell mass density of 25 g/l was obtained.
The stability of this r-DNA E. coli cells in this mode was greatly different from that in shake flask culture repeated. After 6-7 generation 80-90% of total cells in broth was stable in shake flask, but in this mode only 40-50% was stable.