bioreactor studies of heterologous protein production by ...

53.3. SimuIated Results for Present Recombinant Yeast
The batch culture model consists of 5 differential qations and 10 analyticai equations.
These 15 equations must be solved simultaneously in order to evaluate the fermentation
variables, which are glucose concentration (G), total cell concentration (X), plasmid-
bearing ceii concentration (X'), ethanol concentration (E), recombinant protein
concentration (P) and the fraction of plasmid-bearing œiis (F). The differential equations
were solved numericaily using a fourth order Rnnge-Kutta algorithm whiîe Newton's
method was used for solving the anaiyticai eqnations. The step size taken was 0.2 hour.
Solution of the model equations was pmgrammed in C code and was mn in a Turbo Ccç
environment (Borland hc.). A phtom of the source code is presented in AppendUt F.
Graphical representation of the mode1 output and experirnental data were canied out with
Excel software. A cornparison beniveen the model-simulated and experimental results for
the present ncornbhant yeast (C46apGAC9) culture in airiin bioreactor is presented in
Figure 5.2.
Figure 5.2 shows exceRent agreement between mode1 predictions and experimental
mulu for glucose, ceii mas, ethanol glumamylase (recombinant protein) and fiaction of
plasmid-bearing cek during batch fermentation of recombinant S. cerevisioe soain
C468lpGAC9. Using the modifieci Monod equation, the mode1 successfuny predicted
diauxic growth, glucose consumption, ethanol production and ethanol utilharion after
glucose exhausrion. With the assumption that the formation of recombinant protein is only