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Kinetic of Whole Cell Equation

1. Monod Equation
1.1. History
During the last half century, the concepts in microbial growth kinetics have been
dominated by the relatively simple semi-empirical model proposed by Monod. The Monod
model di ers from the primary models in the way that it introduces the concept of a growth
controlling substrate. This sub-strate is called limiting substrate to indicate that the microbial
growth rate is dictated by the actual concentration of a particular metabolite. Whereas there is a
causal relationship between the exhaustion of the limiting substrate and the end of growth, the
Monod model may be considered deterministic.
In the 1930s and 1940s, Jacques Monod performed experiments on bacte-ria feeding on a
single limiting nutrient in order to see if the logistic equation accurately described bacterial
growth. He found it did not and therefore he developed a new model to describe his results. If
S(t) denotes the concentration (kg/m3) of the nutrient in the media at time t, his experiments
suggested that the specific growth rate.

tration X(t) is described by.

The expression above is often called the Monod function.

1.2. Concept
We have already know the Monod equation from the explanation before:

As a function of S it is monotonically increasing with limit max as S. The parameter

max is therefore called maximum specific growth rate and KS is called half-saturation constant,
or a nity constant, because when S(t) = KS the speci c growth rate becomes max, that is half the
maximum speci c growth rate. The key feature of the Monod function is that the speci c growth
rate increases with nutrient concentration S as expected, but it levels out at low nutrient
concentrations. For high substrate concentration, the relation above approaches zero order and
the rate of reaction is thus independent of sub-strate concentration and is constant at the
maximum value. In this case the growth is said to be in conditions of non-limiting nutrients.
The link between growth and substrate utilization was made by Monod, who linearly
related the speci c rate of biomass growth and the specific rate of substrate consumption through
the yield coeffcient YXS, a measure for the conversion efficiency of a growth substrate into cell
material. The relation between cell growth and substrate consumption is given by:
The complete Monod model is then composed by two coupled differential equations with
two model parameters:

That can be solved if the initial value X0 and S0 are given. In figure bellow, the solution for the
cell and the substrate concentrations is plotted: we can observe that cell growth gradually stops
as the substrate is consumed.
Although very simple, the Monod model often describes experimental data for growth
rates reasonably well.

1.3. Modified Concept

a. Multiple-substrate Monod Kinetics
If we want to describe the in uence of many substrates, for example two substrates S 1 and
S2, we can consider the following form of the Monod

In this model either substrate may be limiting under conditions when the other substrate
is in excess. An example of such kinetics is the simultaneous requirement of glucose and oxygen
by aerobically growing organism.
b. Double-Monod Kinetics

The Monod equation can also be written for two substrates that can be used by the
cell with parallel reactions:

An example of this kinetics is the parallel use of alternative carbon substrates, such as
glucose and glutamine.

c. Diauxic Monod Growth

In a medium containing two carbon sources, cells can display a growth curve that is
called diauxic. Diauxic growth can be observed in many organisms. Monod first observed
this phenomenon when he grew Escherichia Coli in a medium containing glucose and
lactose. Under these conditions, glucose is rst utilized as energy source and after the
exhaustion of glucose, lactose is utilized. This led him to conclude that some bacteria
preferentially utilize certain carbon substrates.
Diauxic Monod growth can be modeled, for two substrates S1 and S2, by the relation

In this way the consumption of substrate S2 will be inhibited until S1 is exhausted, for
suitably low values of inhibition constant KI.
2. Gompetz Equation
2.1. History
Benjamin Gompertz came from a family of merchants who left Holland and settled in
England. He was one of three sons born in England to a Dutch family which, although from
Holland, was Jewish. His mother, Leah Cohen, was the second wife of the diamond merchant
Solomon Barent Gompertz. Benjamin was self educated, learning mathematics by reading
Newton and Maclaurin. He had to take this route because he was denied admission to
universities since he was Jewish. In fact he was greatly helped in his mathematical education
by the Spitalfields Mathematical Society which was later to become the London
Mathematical Society. Gompertz, writing to De Morgan, explained how he came to be a
member of the Society.
On 10 October 1810 Gompertz married Abigail Montefiore, who came from a
wealthy Jewish family with strong links with the stock exchange, at the Hambro Synagogue,
London. They had three children, a daughter Justina Lydia born in 1811, a son Joseph born in
1814, and a second daughter Juliana born one year later. Gompertz himself joined the stock
exchange in 1810 and he became a Fellow of the Royal Society in 1819. The following year
he read a paper to the Society which applied the differential calculus to the calculation of life
expectancy. In 1824, the year his 10 year old son died, Gompertz was appointed as actuary
and head clerk of the Alliance Assurance Company. This company had been set up by Sir
Moses Montefiore, the brother of Gompertz's wife, at least in part to put Gompertz's
mathematical and actuarial skills to good use.
Gompertz applied the calculus to actuarial questions and he is best remembered for
Gompertz's Law of Mortality. Gompertz, in 1825, showed that the mortality rate increases in
a geometric progression. Hence, when death rates are plotted on a logarithmic scale, a
straight line known as the Gompertz function is obtained. It is the most informative actuarial
function for investigating the ageing process. The slope of the Gompertz function line
indicates the rate of actuarial ageing. The differences in longevity between species are the
result primarily of differences in the rate of ageing and are therefore expressed in differences
in slope of the Gompertz function. His expertise on life tables was recognised at the highest

2.2. Concept
The Gompertz function is a sigmoid function, as the logistic curve. The curve shows a
slowest growth at the start and at the end of the time period. In contrast to the logistic
function in which both the asymptotes are approached by the curve symmetrically, in the
Gompertz model the future value asymptote of the function is approached much more
gradually by the curve than the lower valued asymptote.
The Gompertz curve has the following expression (Figure 1.4):

It is possible to verify immediately that a is the upper asymptotic value, b is the x

displacement and c sets the growth rate. Moreover, the initial cell concentration is X0 = a exp
2.3. Logistic Equation
2.4. History
A typical application of the logistic equation is a common model of population
growth (see also population dynamics), originally due to Pierre-Franois Verhulst in 1838,
where the rate of reproduction is proportional to both the existing population and the amount
of available resources, all else being equal.
The Verhulst equation was published after Verhulst had read Thomas Malthus' An
Essay on the Principle of Population. Verhulst derived his logistic equation to describe the
self-limiting growth of a biological population. The equation was rediscovered in 1911 by A.
G. McKendrick for the growth of bacteria in broth and experimentally tested using a
technique for nonlinear parameter estimation. The equation is also sometimes called the
Verhulst-Pearl equation following its rediscovery in 1920 by Raymond Pearl (18791940)
and Lowell Reed (18881966) of the Johns Hopkins University. Another scientist, Alfred J.
Lotka derived the equation again in 1925, calling it the law of population growth.

2.5. Concept
A second model that we can introduce is the logistic model, that was rst published by
Pierre-Francois Verhulst in 1838 after he read Malthus' work. It takes the following form:

where now, besides , there is a second parameter K (kgcell/m3), often called carrying
capacity, which is the maximum concentration of cells that the environment can support. The
logistic equation has the major disadvantage that the carrying capacity K cannot be measured
other than by growing the organism until it stops growing. Moreover, there is no theoretical
under-pinning for it.
The logistic equation can be integrated exactly and has solution (Figure 1.3).

4. Modified Concept for Gompertz and Logistic Method

Sigmoidal functions have been the most popular ones used to fit microbial growth
data since these functions consist of three phases, similar to the microbial growth curve. The
most commonly used in the literature are the modified logistic model:

and the modi ed Gompertz model:

where X(t) is the number of cells at time t, and A, B, C and M are model parameters. The
original logistic and Gompertz functions are considered to be mechanistic; however, the modi
ed functions are empirical: it is difficult, in fact, to give an interpretation of the model
parameters, that have to be statistically estimated from experimental results. The Gompertz
equation and its modified version have been used extensively by researchers to fit a wide
variety of growth curves from different microorganisms with good results.
There are, however, some limitations associated with the use of these functions: the
Gompertz rate max is always the maximum rate, regardless of the actual culture medium
composition, and it occurs at an arbitrary point of inflection; thus the generation time is not
estimated properly. In addition, since the slope of the function cannot be zero, the lower
asymptote must be lower than the inoculum level, giving a negative lag phase duration for
some data sets.
The correlation of those equations is the growth rate parameter. it is in monod equation
whereas it is called B in gompertz and logistic equations. Thus the graphics among those
equiation is typically the same.