UNIVERSITY OF MINDANAO

COLLEGE OF ENGINEERING EDUCATION

“Kinetics Model of Growth and Product Formation”

A written report under the study of Biochemical Engineering

Submitted by:

Jeffrey G. Esquilona

Submitted to:

ENGR. ARJAN C. LINGAYA

INSTRUCTOR
Kinetics and Modelling

Kinetics is a study that deals with rate of the reaction. It is based on the mechanisms of any
processes-physical, chemical or biological. The chemical kinetics deals with how the rate of
reaction is dependent upon the concentration of the reactants. In a biochemical reaction, kinetics
is a little complicated. A living cell, during fermentation or any biological processes, require
essential nutrients and suitable environment to survive. Hence a biochemical reaction proceeds
with the intervention of microbial cells in a liquid medium containing nutritive sources under
conditions like pH, temperature. The cells multiply and grow, consuming a part of substrate and
other necessary components from the fermentation broth. Cell growth is associated with two
processes namely, uptake of some material from the cell’s environment and consuming it into
metabolic end products. (D.G Rao, 2001)

Certain parameters phenomena that determine cell population kinetics are the
characteristics of culture broth, nutrients and substrates used for growth and production of
metabolites, cell to cell heterogeneity, microbial cells of different ages manifesting metabolic
activities and characterization of biochemical pathway. These complex parameters make it
difficult to formulate a simple kinetic model for cellular activities (Bailley and Ollis, 1986). A
kinetic model describes the behaviour of the cellular processes through possible mathematical
equations and it serves to be a very effective tool to test and eliminate the extremities. Different
kinetic models have been proposed in several research works for microbial growth, substrate
utilisation and product formation in various fermentation modes. In order to construct a simple
kinetic model, different approximation and representations of cellular population are taken into
consideration. An individual cell in a liquid broth is a complicated multi component system, which
is not spatially homogenous even at a single cell level. Nutrient solution used for the inoculum
growth and production is also a multi component system containing all the complex nutrients for
cell growth and accumulates various products as the result of metabolic activities. According to
number of components used in microbial representations and considering cells as heterogeneous
mass or wholly as average cell clusters, different perspective are put forward for cell population
kinetic representations . See figure 1, below
Figure 1. Certain important parameters, phenomena, and interactions which determine cell
population kinetics ( Bailley and Ollis,1986)

Environment (medium) Cell population

Multicomponent Nutrients Multicomponent
Reaction in solution Substrates cell-to-cell
Acid-base equilibria Products heterogeneity
Variable pH, T… Multireaction
Changing rheological properties (viscosity,..) Heat Internal Controls
Multiphase (G-L,L-L, G-L-L) Mechanical Adaptability
Spatial nonunifomity interactions Stochastic and genetic drift

Structured model is one perspective in which the microbial cells are considered as
multicomponent systems. When cell population is treated as one component system, it is referred
to as unstructured model. The rate of reaction depends only on the parameters inside the fermenter.
These models only contain growth, substrate consumption and product formation kinetics. Cell to
cell heterogeneity and discrete cells compose a multi component entity, constituting ultimately a
segregated perspective. An unsegregated view considers average cellular properties. In actual
cellular cases, the situation is a structured and segregated one. In balanced growth of cells, the
metabolic activities are coordinated in such a way that the average cell composition is not
influenced by increase in cell mass. In such cases, models that do not consider the multi component
nature of cells are necessary. Hence unsegregated, unstructured model is the most idealized
situation when analyzing the growth of cells (Bailley and Ollis, 1986). See figure 2, below

Unstructured Structured

Most Idealized case Balanced Growth Mulicomponent average cell description

Unsegregated Cell population treated as one component solute

(approximation) "average cell"
"average cell" approx imation
approx imation

Balanced Growth Multicomponent description of cell-to-cell heterogeniety

Segregated
single component, heterogeneous individuals cells (approximation) Actual case

Figure 2. Different perspectives for cell population kinetic representation (Adapted from
Bailley and Ollis,1986)
Growth Kinetics Models

The growth of microbial cells include four major phases namely lag phase, exponential
phase, stationary phase and the decline phase, which had been previously described. An emphasis
on the exponential or logarithmic phase had been given in this particular work, since the production
of the product, exopolysaccharide, is found maximum and directly proportional to the microbial
cell growth.

Various Model have been used for studying growth kinetics.

Malthus Model

The simplest cell growth model is the Malthusian model commonly known as exponential
law. The model is named after Thomas Robert Malthus, who wrote An Essay on the Principle of
Population (1798). In a batch fermentation operated under ideal conditions the concentration and
weight of biomass increases proportionally with increase in time. Hence it could be said that all
the cells have the same probability to multiply. Thus the overall rate of biomass formation is
proportional to the biomass itself. For a batch system, this is equivalent to
𝒅𝒙
= µ𝒙
𝒅𝒕

Where x is the mass of cells per unit volume, µ is the proportionality constant known as 'specific
growth rate' (h-1) and t is the time (h).

Integrating, by first order kinetics

X=xoeµt
The demerit of this model is that it ignores the substrate needed for its growth and

that the resources are constrained.

Contois Model

Contois model is another unstructured model that depends upon substrate and cell
concentration which is given as
𝑺
µ=µmax
𝑩𝒙+𝑺
Tessier Model

Tessier model is another growth kinetic model that also rely upon the substrate
concentration and is explained by,

µ=µmax(1-e-s/Ks)
Moser Model

Moser model relies upon the growth rate and substrate concentration and the two parameter
model is depicted as

µ=µmax(1+Ks S-λ)-1

Note: Moser and Tessier model render algebraic solution of the growth equations much more
difficult than the Monod model .

Product Formation Kinetics Model

The type of kinetic description that may be employed for product formation by cell
population parallel those used to describe cell population growth. The simplest types of product
formation kinetics arise where there is a simple stoichiometric connection between product
formation and substrate utilization or cell growth. The rate of production of the product parallels
the rate of cell growth. Substrate concentration falls continuously as fermentation proceeds. Such
product formation kinetics is sometimes called as growth associated. In many fermentation,
involving secondary metabolite, significant product formation does not occur until relatively late
in a batch cultivation, that is, production happens in the late exponential phase or during the
stationary phase. Production rate is proportional to cell concentration rather than growth rate. This
kind of kinetics is referred to as non growth associated model.

A typical and widely used product kinetic model is Luedeking- Piret model (1959), which
is an unstructured approach contributed to both growth and non growth associated phenomena for
product formation. This model was originally developed for the formation of lactic acid by
Lactobacillus delbruckeii and the equation is given as

rfp=αrfx+βx

where rfp is the rate of product formation , αrfx is the rate of biomass formation and α and β are
the kinetic constants of Luedeking- Piret model. This two-parameter expression has proven
extremely useful and versatile in fitting product formation data from different fermentations. This
is an expected kinetic form when the product is the result of energy yielding metabolism.
 According to this model, the product formation rate depends linearly upon the growth rate
and the cell concentration
𝒅𝑷 𝒅𝒙
=α +βx
𝒅𝒕 𝒅𝒕

The Luedeking-piret kinetic parameters, α and β depend upon and vary with the
fermentation dynamics. The kinetic constant β can be evaluated from the stationary phase of batch
volume, which implies
𝒅𝑷
( )𝒔𝒕𝒂𝒕𝒊𝒐𝒏𝒂𝒓𝒚 𝒑𝒉𝒂𝒔𝒆
β= 𝒅𝒕
𝑿𝒔

where xs, is the cell concentration at the stationary phase.

Reference:

KINETICS, MICROBIAL GROWTH,

http://people.math.gatech.edu/~weiss/uploads/5/8/6/1/58618765/panikov_kinetics_microbial_gro

wth.pdf

Doran, P. M. (1995). Bioprocess Engineering Principles. San Diego, California: Academic Press
Limited.

Bailey, J.E and Ollis, D.F (1986). Biochemical Engineering Fundamentals. Second Edition.Edn,
McGraw-Hill, Inc., New York, p.12

Rao, D.G,(2001). Fundamentals of Food Engineering. Washington Publishing Company.

Wachington D.C