Example 73 An unstructured model describing the growth of
is an industrially important microorganism used for production of baker’s yeast and ethanol
and today also for production of recombinant proteins. Sonnleitner and Kappeli (1986) proposed a simple
for the growth of this organism, and in this example we are going to discuss this model.
However, before the model is discussed some fundamental aspects of the fermentation physiology of
will have to be reviewed.
As already discussed in Example 3.5 and further in Example 5.4 aerobic growth of
glucose involves a mixed metabolism, with both respiration and fermentation being active. At high
glucose uptake rates there is a limitation in the respiratory pathway, which results in an overflow
metabolism towards ethanol. The exact location of the limitation has not been identified, but it is
probably at the pyruvate node (Pronk
1996). The glucose uptake rate at which fermentative
metabolism is initiated is often referred to as the critical glucose uptake rate, and the critical glucose
uptake rate is found to depend on the oxygen concentration. Thus, at low dissolved oxygen
concentrations the critical glucose uptake rate is lower than at high dissolved oxygen concentrations (and
clearly at anaerobic conditions there is only fermentative metabolism corresponding to the critical
glucose uptake rate being zero). The influence of dissolved oxygen concentration on the critical glucose
uptake rate is often referred to as the Pasteur effect. A simple verbal model for the mixed metabolism is
given in Fig. 7.7. When
is grown in an aerobic, glucose-limited chemostat two distinct growth
regimes are observed (see Fig. 7.8): (1) at low dilution rates all (or most) of the glucose is converted to
biomass and carbon dioxide, and (2) at high dilution rates ethanol is formed in addition to biomass and
carbon dioxide. As observed in Fig. 7.8, the shift to ethanol formation results in a dramatic decrease in the
biomass yield from glucose.
In Fig. 7.8 the specific oxygen uptake rate is observed to increase with the dilution rate up to A™,
whereafter it is approximately constant, while the specific carbon dioxide formation rapidly increases.
Sometimes there is a more distinct decrease in the specific oxygen uptake rate above the critical dilution
rate, but this depends on the strain and the operating conditions. The shift in metabolism at
nt is normally
referred to as the Crabtree effect, and it is a consequence of a bottleneck in the oxidation of pyruvate and
repression of the oxidative system by high glucose concentrations. The bottleneck in the oxidation of
pyruvate is illustrated in Fig. 7.7, where the flux through the glycolysis (indicated by the arrow) has to be
smaller than the oxidative capacity of the cell (indicated by the bottleneck) if ethanol formation is to be
avoided. If the glucose flux is larger than permitted by the bottleneck, the excess glucose is metabolized by
the fermentative metabolism, and ethanol is formed.