Fed-Batch Cultivation - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 687

without introducing any disturbances to the culture. Moreover, the rate of heat production is
stoichiometrically related to the rate of substrate consumption and product, including
biomass formation. In many cases, it can be replaced by exhaust gas analysis, although
this approach cannot be considered in anaerobic processes which proceed without formation
of gaseous products.
This technique has been proved successful to indirectly determine the substrate and
product concentrations continuously during aerobic batch growth of S. cerevisiae with
glucose as the carbon and energy source. In the presence of this substrate, this yeast shows
diauxic growth by initially consuming the glucose with concomitant production of ethanol
and then, once glucose is depleted, using the produced ethanol as an energy source. Calo-
rimetry can then be used to control the feed rate in such a way that ethanol formation is
avoided.
Another interesting description of a temperature-based controlled reactor follows
a stability criterion. The range of operation is controlled by the reactant feed temperature,
which can be controlled by the flow rate of the cooling medium. Although the study has
been performed in a chemical reactor, the concepts can be easily extended to a biotransforma-
tion process.
13.7.2. Specific Growth Rate
For the production of a growth-associated product, the production of a certain product is
related with the specific growth rate of the producing microorganism. This is a case where
chemostat (or CSTR) cultivation could be optimum should all the stability conditions met.
Consequently, it is of interest to feed the fermentor in such a way that the specific growth
rate remains constant. Such is the case of the production of hepatitis B surface antigen by
S. cerevisiae . The yield of the antigen can be a factor of 10 times that of the fed-batch cultiva-
tion for the same final volume and total substrate added. Care should be given to the value of
the chosen specific growth rate, because cells may not be “activated” easily, stress proteases
can be produced that may degrade the product and also there might be a threshold value of
specific growth rate above which there is production of by-products.
13.7.3. Substrate (Carbon and Nitrogen Source)
Substrate is a particularly important parameter to control due to eventually associated
growth inhibitions and to increase the effectiveness of the carbon flux, by reducing the
amount of by-products formed and the amount of carbon dioxide evolved.
13.7.4. By-product concentration
We refer a by-product as a primary product from a side reaction. Therefore, the production
of by-products is undesirable because it reduces the efficacy of the carbon flux in a fermenta-
tion. The production of these components takes place whenever the substrate is provided in
quantities that exceed the oxidative capacity of the cells. This approach has been used in the
fermentation of S. cerevisiae , in which acid production rate is used to provide online estimates