Influence of macromixing on plasmid stability during batch fermentation with recombinant bacteria

Abstract

<span style="font-size:11.0pt;line-height:115%; font-family:" calibri","sans-serif";mso-ascii-theme-font:minor-latin;mso-fareast-font-family:="" "dejavu="" sans";mso-hansi-theme-font:minor-latin;mso-bidi-font-family:mangal;="" mso-bidi-theme-font:minor-bidi;color:#00000a;mso-ansi-language:en-us;="" mso-fareast-language:en-us;mso-bidi-language:ar-sa"="">Macromixing in a batch bioreactor has been analyzed through an extended version of a two-region model proposed earlier. Two internal dilution rates characterize the degree of macromixing. Computations for an <i style="mso-bidi-font-style:normal">Escherichia coli</i> culture containing the plasmid pBR Eco gap show that in order to maximize the average concentration (or mass fraction) of plasmid-containing cells, the region into which the inoculums is introduced should be poorly (or perfectly) mixed while the other region should be perfectly (or poorly) mixed. Time-domain profiles for the two regions suggest that plasmid-containing cells become homogeneously distributed faster than plasmid-free cells. Comparison of the regional profiles for the cases of the largest average concentration and the largest-average mass fraction of plasmid-containing cells reveal differences which indicate that a partially macromixed bioreactor may be an optimal choice.</span>