Cell Metabolism - Bioprocess Engineering: Kinetics, Biosystems, Sustainability and Reactor Design - page 497

different glucose concentrations. This illustrates a general problem when a genetically struc-
tured model is combined with overall models for cell function: Certain mechanisms may be
described in great detail d in this case, the gene expression, whereas other processes are
described by completely empirical expressions. Hereby the performance of the overall model
is largely determined by the performance of the empirical expressions in the model, and it
may be adequate to apply a simpler model for the gene expression.
The real strength of the genetic approach is, however, not its linkage to the overall growth
model but rather the possibility offered to analyze the influence of specific model parameters
on the process. Thus, using the above model, the importance of the different equilibrium
constants, which are related to the binding affinities, e.g. of the repressor to the operator, can
be studied in detail. This can be done by comparison with experimental data for the mRNA
level, preferably at conditions where the overall cell activity is the same in all experiments.
One should now see how the cellular control strategy emerges and how to model it math-
ematically. If the cell has an energetically favorable carbon-energy source available, it will not
expend significant energy to create a pathway for utilization of a less favorable carbon-
energy source. If, however, energy levels are low, then it seeks an alternative carbon-energy
source. If and only if lactose is present will it activate the pathway necessary to utilize it.
Catabolite repression is a global response that affects more than lactose utilization.
Furthermore, even for lactose, the glucose effect can work at levels other than genetic. The
presence of glucose inhibits the uptake of lactose, even when an active uptake system exists.
This is called inducer exclusion.
The role of global regulatory systems is still emerging. One concept is that of a regulon.
Many noncontiguous gene products under the control of separate promoters can be coordi-
nately expressed in a regulon. The best-studied regulon is the heat shock regulon. The cell has
a specific response to a sudden increase in temperature (or other stresses that result in
abnormal protein formation or membrane disruption), which results in the elevated
synthesis of specific proteins. Evidence now exists that this regulon works by employing
the induction of an alternative sigma factor, which leads to high levels of transcription
from promoters that do not readily recognize the normal E. coli s factor. Examples of other
regulons involve nitrogen and phosphate starvation, as well as a switch from aerobic to
anaerobic conditions.
Although many genes are regulated, others are not. Unregulated genes are termed consti-
tutive, which means that their gene products are made at a relatively constant rate irrespec-
tive of changes in growth conditions. Constitutive gene products are those that a cell expects
to utilize under almost any condition; the enzymes involved in glycolysis are an example.
Example 10-1.
Diauxic growth is a term to describe the sequential use of two different carbon-energy sour-
ces. Industrially, diauxic growth is observed when fermenting a mixture of sugars, such as
those obtained from the hydrolysis of biomass. The classic example of diauxic growth is
growth of E. coli on a glucose e lactose mixture. Observations on this system led to formula-
tion of the operon hypothesis and the basis for a Nobel prize (for J. Monod and F. Jacob).
Consider the plot in Fig. 10.14 , where the utilization of glucose and lactose and the growth
of a culture are depicted for a batch culture (batch reactor). As we will discuss in more detail
in Chapter 11, the amount of biomass in a culture, X, accumulates exponentially. Note that at