Models with growth inhibitors.

1. Substrate inhibition: At high substrate concentrations, microbial growth rate is inhibited by the
substrate. As in enzyme kinetics, substrate inhibition of growth may be competitive or
noncompetitive. If a single-substrate enzyme-catalyzed reaction is the rate-limiting step in
microbial growth, then inhibition of enzyme activity results in inhibition of microbial growth by
the same pattern. The major substrate-inhibition patterns and expressions are as follows:

2. Product inhibition: High concentrations of product can be inhibitory for microbial growth.
Product inhibition may be competitive or noncompetitive, and in some cases when the underlying
mechanism is not known, the inhibited growth rate is approximated to exponential or linear decay
expressions. Important examples of the product inhibition rate expression are as follows:

3. Inhibition by toxic compounds: The following rate expressions are used for competitive,
noncompetitive, and uncompetitive inhibition of growth in analogy to enzyme inhibition.
The Logistic Equation.
The logistic equation. When plotted on arithmetic paper, the batch growth curve assumes a
sigmoidal shape. This shape can be predicted by combining the Monod equation with the growth equation
and an equation for the yield of cell mass based on substrate consumption.

The relationship between microbial growth yield and substrate consumption is

Requires a predetermined knowledge of the maximum cell mass in a particular

environment. This maximum cell mass we will denote as ; it is identical to the ecological concept of
carrying capacity.

Is implicit in its dependence on S.

Logistic equations are a set of equations that characterize growth in terms of carrying capacity.
The usual approach is based on a formulation in which the specific growth rate is related to the amount of
unused carrying capacity:
 Example:
Ethanol formation from glucose is accomplished in a batch culture of Saccharomyces cerevisiae,
and the following data were obtained.

a. By fitting the biomass data to the logistic equation, determine the carrying- capacity
coefficient k.
b. Determine yield coefficient / and / .

Solution:
1
a. =
(1 )

Is the average biomass concentration during

Is about 10.8 g/L, since growth is almost complete at 30h.
 k = 0.24/h.
b. The yields are estimated directly from the data as:

(49 0)
/ = = = .
(2 100)
(10.7 0.5)
/ = = = .
(2 100)
The above estimate of / is only approximate, as maintenance effects and endogenous
metabolism have been neglected.

Growth Models for Filamentous Organisms

Filamentous organisms such as molds often form microbial pellets at high cell densities in
suspension culture. Cells growing inside pellets may be subject to diffusion limitations. The growth models
of molds should include the simultaneous diffusion and consumption of nutrients within the pellet at large
pellet sizes.
Alternatively, filamentous cells can grow on the surface of a moist solid. Such growth is usually a
complicated process, involving not only growth kinetics but the diffusion of nutrients and toxic metabolic
by-products. However, for an isolated colony growing on a rich medium, we can ignore some of these
complications.
In the absence of mass-transfer limitations, it has been observed that the radius of a microbial pellet
in a submerged culture or of a mold colony growing on an agar surface increases linearly with time.
 The initial biomass, , is usually very small compared to M, and therefore M varies with t3.

Cybernetic Models
Another modeling approach has been developed primarily to predict growth under conditions when
several substrates are available. These substrates may be complementary (e.g., carbon or nitrogen) or
substitutable. One approach to modeling growth on multiple substrates is a cybernetic approach.
Cybernetic means that a process is goal seeking (e.g., maximization of growth rate). While this
approach was initially motivated by a desire to predict the response of a microbial culture to growth on a
set of substitutable carbon sources, it has been expanded to provide an alternative method of identifying the
regulatory structure of a complex biochemical reaction network (such as cellular metabolism) in a simple
manner. Typically a single objective, such as maximum growth rate, is chosen and an objective-oriented
mathematical analysis is employed. This analysis is similar to many economic analyses for resource
distribution. For many practical situations this approach describes satisfactorily growth of a culture on a
complex medium. However, the potential power of this approach is now being realized in efforts in
metabolic engineering and in relating information on DNA sequences in an organism to physiologic
function. This approach has limitations, as the objective function for any organism is maximizing its long-
term survival as a species. Maximization of growth rate or of growth yield are really sub-objectives which
can dominate under some environmental conditions; these conditions are often of great interest to the
bioprocess engineer.
Consequently, the cybernetic approach is often a valuable tool. It is too complex for us to describe
in detail in this book; the interested reader may consult the references at the end of this chapter.