Optimal fed-batch operation of recombinant cells subject to plasmid instability and death.
Optimal feed rate strategy is studied for fed-batch culture of recombinant cells with plasmid instability and with different death rates for the plasmid-free cells (PFC) and plasmid-bearing cells (PBC). Most of the fed-batch fermentation is known to have first-order singularity and therefore a single singular arc. However, this study shows that a singular arc with second-order singularity and therefore two distinct singular arcs are possible for a recombinant cell process if PFC and PBC are subjected to death, and their specific growth rates are proportional to each other. Two types of singular arcs are elucidated and analyzed. The optimal policies over the singular arcs are theoretically explored as these findings reveal qualitative information on the singular arc, which is critically important in providing the optimal initial conditions in numerical computation of optimal feed rate profile.
Shin
Hwa Sung
HS
Department of Chemical Engineering and Materials Science, University of California, Irvine, CA 92697, USA. hsshin@uci.edu
Lim
Henry C
HC
D000465:Algorithms; D001671:Biochemistry / Q000379:methods; D019149:Bioreactors; D004247:DNA / Q000378:metabolism*; D005285:Fermentation; D005947:Glucose / Q000737:chemistry; D007218:Industrial Microbiology / Q000379:methods*; D007700:Kinetics; D008956:Models, Chemical; D015233:Models, Statistical; D008962:Models, Theoretical; D010957:Plasmids / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013997:Time Factors
D004247:DNA; D005947:Glucose