Unstructured Kinetic model

Model
 Unstructured kinetic model
• Microbial kinetics and energetics are discussed in connection with the
formulation of unstructured growth models.

• The development of microbial energetics and the use of macroscopic

methods in the study of microbial growth

• A simple unstructured model based on Monod kinetics and the linear

relation for substrate consumption is evaluated with reference to extensive
experimental and simulation data obtained in batch, fed-batch, and
continuous cultivation modes
 Unstructured kinetic model
• These models are based on conservation equations for cell mass,
nutrients, metabolites, and species generation/consumption rates.

Most of the UKMs can be divided into three terms:

• rate expressions for cell growth
• rate expressions for nutrient uptake,
• and rate expressions for metabolite production.
Title
 Monod model
• The Monod model was first introduced by Jacques Monod in
1942 to describe the relationship between specific growth rate
and substrate utilization rate in a bioreactor (Monod, 1949).
• The model can be defined in two forms: based on substrate
concentration only, and based on both substrate and biomass
concentration.
• The two forms of the model are defined by
 Monod model assumptions
The Monod model has 5 limitations as described by Kong (2017).
• The 1st limitation is observed at high substrate concentration. At high substrate
concentration, the maximum specific growth rate is independent of the
substrate concentration.
• The 2nd limitation is observed at low substrate concentration. At low substrate
concentration, growth is dependant on substrate concentration.
• 3rd limitation is that the Monod model cannot be applied when a substrate
exhibits inhibition (Kim et al., (2005); Shukor (2014); Han and Levenspiel (1988).
• 4th the Monod model does not account for the fact that cells may require
substrate for maintenance during the death phase.
• The 5th limitation is that the model does not account for the lag and death
phase during the growth phase (Kong (2017), and Mrwebi (2004 ).
 Blackman model
• The Blackman model was introduced by Blackman in 1905 (Blackman,
1905).
• The model is similar to the Monod model in terms of its assumptions.
• At low substrate concentration, growth is dependant on substrate and
at high substrate concentration, growth is independent of substrate
concentration.
• At high substrate concentration, some nutrients are limiting (Kong,
2017).
• The model has been described as being capable of making a sharp
transition from first order kinetics to zero order kinetics (Mrwebi, 2004).
 Haldane model
• Haldane model was introduced by Haldane in 1930.
• The model is viewed as an extension of the Monod model.
• The model introduces a 3rd constant Ki that deals with specific growth rate
inhibition at low and high substrate concentration.
• Ki is the inhibition constant which is equal to the highest substrate
concentration at which the specific growth rate is equal to one half maximum
growth rate in the absence of an inhibition.
• Kong (2017) reported that at high substrate concentration, specific growth rate
of an organism may be hindered by the presence of toxic substrate.
• With the inclusion of the inhibition constant, the model is capable of handling
both toxic and non-toxic substrate. The Haldane model is defined by equation
 Teissier model
• The Teissier model was introduced in 1942 (Teissier, 1942).
• The Teissier model is also known as the Exponential model that describes the
specific growth rate as a function of continuous substrate concentration.
• The model is similar to the Monod model, and Blackman model.
• Experimental data fitted on the Teissier model was observed to lie in between
the Monod model, and Blackman model (Kong, 2017).
• Just like the Monod model, Blackman model, and Moser models, the Teissier
model is not capable of describing cell growth inhibition. Hence it is not capable
of describing the lag and death phase.
• The Teissier model is defined by eqn
 Moser model
• The Moser model is an unstructured model based on substrate
concentration only introduced in 1958 by Herman Moser (Moser,
1958).
• The model is an extension of the Monod model.
• The Moser model introduced a parameter constant (n) on the Monod
model. The parameter (n) is an adjustable parameter that provides
flexibility in fitting experimental data and dynamic behaviour in the
bioreactor (Mahanta et al., 2014).
• The Moser model is considered to be a better model than the Monod
model because the parameter (n) can be adjusted to fit the
experimental data (Kong, 2017).
 Conclusion
• Literature shows that there are a number of unstructured models that can be used to describe kinetic
growth rate. Based on the information from the literature, all the kinetic growth models were capable
of describing growth rate.

• The only distinction is on the conducting of experiments. The collection of data, analysing of data,
and environmental conditions will have an impact on the performance of each kinetic growth model.

• The most notable model the performed well was the Haldane model.

• The model was the most reported model in the literature with success on different types of substrate.

• The Monod, Moser, Teissier, and Contois model struggle to describe the lag and death phase during
growth however they performed well as reported in the literature .
 Structured kinetic model

• Structured kinetic models (SKMs) describe changes in cell

population (intracellular metabolism)
• Attempts to account for unbalanced growth of micro organisms
• Classified into morphologically structured models, chemically
structured models, genetically structured models, and
metabolically structured models 
• Structured models consider the kinetics of nutrient consumption
and product formation
• SKMs can be classified as dynamic and structural 
 Structured kinetic model- types

• Morphologically structured models consider the kinetics of nutrient

consumption and product formation. These models consider different cell types
as living species in terms of the role that they play in the overall reaction.
• Chemically structured models consider the effects of chemical species in
fermentation kinetics; all viable cells are functionally similar, and all the
fermentation rates and transport phenomena parameters are accounted for.
• Genetically structured models assume molecular mechanism knowledge. The
model includes the rate of expression of an operator-regulated gene and kinetic
equations for the transcription, translation, and folding processes.
• Metabolically structured models provide a better understanding of process
regulation mechanisms such as feedback regulation.
 Compartmental model

Basis of function of parts of cell’s internal machinery

• Williams model
• Model of cellular energetics and metabolism
• Model for aerobic growth
• Models of product formation
• Single cell models
 William’s model

• K (synthetic) and G (genetic) are the 2 compartments

• K- pool of RNA and small metabolites
• G- DNA and protein
• 3rd compartment- external substrate concentration
• K and G are the concentrations of the components in K and G
compartments, Mass balance for the constant reactor volume (VR ),

dxVR / dt  K1SXVR
ie., dx / dt  k1SX
dsVR / dt  1 / Ys k1SXVR
ie., ds / dt  1 / Ys k1SX
• The mass balance based on reactor volume , thus concentration
per cell must be multiplied by the total cell volume per unit reactor
volume, X/ρc
• The synthetic portion of biomass is produced at a rate that is first
order in substrate concentration and depends on cell density (sum
of K and G)
Simulation results of two compartmental model
 Model of Cellular Energetics and Metabolism
• Reactions occur within the cell
• Metabolic pathways- catabolism and anabolism
• Energy production and energy consumption highly regulated
• Consideration of carbon and energy flows will be considered in this
model
Ex: Model for aerobic growth of the yeast Saccharomyces cerevisiae
 carbon and energy metabolism
 Model for Aerobic growth of Yeast
• Respiratory Pathway- glucose + Co2 + Cell mass
• Fermentative Pathway- ethanol + Co2 + Cell mass
• Two stage cell cycle : G1 depends on availablity of limiting
substrate
• Division phase (G2 , M and S Phase): independent of substrate
• A+B) is the total mass (X) and E is ethanol concentration
A  ai 
rA
2 B  a 2 E  CO2
O2  a  a3 E 
rB
2 B  CO2
B
rC
A
S
rA  K1 A
ks  S
E
rB  K 2 A
KE  E
rC  KB
 • Budding process B ͢ A
dB
 2rA  2rB  rC Assumed to be constant
dt Mass balances can be
dA written for each of the
 rA  rB  rC
dt species
dE
 a3 rA  a4 rB
dt
dS
 a1rA
dt
• Yield coefficients to evaluate the constants a1 and a3
• The specific uptake Rates can be calculated from

1 dS  a1rA
qs   
X dt X
1 dE a r  a3 rB
qE   2 A
X dT X
1 dX
 
X dt
• Consequence fraction of B mass increases linearly and the
fraction of A mass decreases with specific growth rate
• At low specific growth rate , total specific substrate uptake rate is
low. Fraction of A mass available to carryout activity is large
 Single cell model

• Incorporation of cell geometry

• Influence of metabolic transport