bioreactor studies of heterologous protein production by ...

observed. After an initial hg, the first exponential growth occurs. In this phase, the
glucose is rnainiy femented to ethanol and aerobic nspiration is repressed due to the
Crabm effect. When the glucose has been depkted another lag phase occws, and then
relatively slower aerobic growth proceeds as the ethanol is metabolized to carbon diolnde
and water. The typicai diauxic growth was shown for the present recombinant yeast
(Figures 4.1 and 4.2). Since the respiratory capacity of recombinant yeast is much Iower
than that of nonrecombinant yeast snallis (Gopa et al., 1989), the Crabtree effect is mon
significant for recombinant yeast strains. Glucose fermentation and ethanol production
WU occur at glucose concentrations pater than O. 1 g/L even under aerobic condition
(Cappella and Dhurjati, 1990).
Knowing the metabolic pathways in yeast is useful for optirniring the recombinant
protein production. It is very iikely that the formation of the recombinant protein is oniy
associated with oxidative pathways. From Table 4.1 it cm be seen that the glucoamylase
yields in the fkst growth phase were much smaller than those in the second growth phase.
The reason is that in the initial growth phase glucose fementation dominated and most of
the glucose was used for ethanol production due to the Crabüee effect, but a low level of
glucose oxidation stiii occurred since repnssion of respiration by glucose is never totai
(Piper and Kirk, 1991). The glucoamylase yield in this phase was low since the celi
growth in the fermentation pathway did not contribute to the production of glucoamylase
and oniy the glucose oxidation pgthway was assoeiated with giucoamylase formation.
This hding was Mer confhed by the experimental resolts of complete anaembic