Corynebacterium glutamicum - JUWEL - Forschungszentrum Jülich

2. Theory
1997; Goncalves et al., 2002; Harada et al., 2002; Schubert et al., 1994).
The current work focuses on the development of mechanistic models and does not
include the use of special black-box modeling techniques, although the actual processes
which take place inside the cells are not regarded in detail, as also mentioned in the next
paragraph.
2.2.2. Macroscopic Modeling
In every model, the real process is simplified. The models can differ in the extent to
which details are described.
In modeling fermentation processes, ’macroscopic models’ describe the whole bioreactor
as one system. These models include equations for the rates of the reactions
taking place, as well as for mass transfer and fluxes into and out of the bioreactor. Usually,
these models do not describe the actual processes taking place inside the organisms,
but use a simplified form which hopefully describes the overall behaviour well enough
for process optimization or process control.
A more detailed description of the processes taking place in the organisms, can be
found in metabolic network models (Bailey, 1991). Here, the enzymatic conversions in
the (relevant) metabolic routes of the cells are modeled. These stoichiometric models
can be used to determine the metabolic fluxes through the cell. Therewith, they can
provide useful information on the actual metabolism and be helpful for the identification
of targets for metabolic engineering 4 . On the other hand, they may prove to be too
complicated for optimization of process conditions or for use in process control.
Going even further into detail in the cell, also the regulation of the expression of genes
and the activity of enzymes could be added to the models. Many different mechanisms of
regulation exist and they are not yet all understood completely. Some examples can be
found in Bajpai et al. (1981); Cheng et al. (2000); Covert and Palsson (2002); Elf et al.
(2001); Herwig and von Stockar (2002).
In the current work, macroscopic models are used, which can be used for optimization
of the process conditions. The detailed description of the intracellular processes is outside
the scope of the project.
2.2.3. Structured and Unstructured Models
Models can also be categorized by the way they are structured.
In models of bioprocesses, the term ’unstructured model’ is usually used for models
which describe the biomass as one (chemical) compound (Fredrickson et al., 1970). In
this simplification, balanced growth is assumed. Structured models use compartimentation,
for instance introducing intracellular metabolite pools as in Birol et al. (2002);
4 Metabolic engineering is the technique of developing improved strains of organisms by modifications
of the genome of the cell. An introduction into this topic can be found in Nielsen (2001)
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