bioreactor studies of heterologous protein production by ...

ecombiit protein synthesis, a mathematical model was developed. The mode1 qaired
43 equations and 48 parameters. Although this mode1 succesSrUny described the obsewed
results for the fermentation of recombinant S. cerevisiae saain AB 103.2fpYaEGF-2!5 in
both batch and fed-batch bioreactors. its complaity poses some practical difficulties (eg.,
parameter estimations) for engineering application.
Hardjito et al. (1992) developed an unstrucnired model to describe the growth
and produc t formation of a recombinant S. cerevisiae ex pressing p-g alactosidase. They
thought that glucose transponed into the ceil was catabolized by both fementative and
oxidative pathways. But they used only one Monod equatioa to express the glucose
uptake process. in addition. it was assumed that ethanol acnimulated in the medium
eould be mer utilized by the cells but the ethanol utilkation rate was inhibited by
avaiiable glucose. Furthemore. they assumed that f3-galactosidase formation &O
foiiowed Monod kinetics. Under these assomptions, a mode1 with 12 equations and 12
parameters was fomulated. With the panuneters determined using a noniinear regression
technique, the mode1 showed good agreement with the experimentd data. The simpiicity
and accuracy were claimed to be the advantage of the model. But it provides us Iittie
insight into the complex biological system.
2.6. Conciuding Remarb
The above sections have descriid the plasmid stabilîty in recombinant S.cermâe at the
molecular, ceIiuiar and engineering ïevels The genetic and environmentai factors which