2. Constraint-based modeling: A mechanistic-driven approach
Cell phenotype depends on various interlaced mechanisms such as
metabolism and transcriptional regulation. Kinetic and constraint-based
modeling are two main mechanistic approaches in analyzing the principles
governing an organism’s metabolism and growth [27]. Kinetic models
help to understand the dynamic behavior of biological systems. In this
approach, the relationship between metabolites is expressed through
kinetic laws represented as the ordinary differential equations (ODE)
[28]. However, kinetic modeling requires costly and time-consuming
efforts to determine sophisticated kinetic parameters (e.g., enzymatic
constants and metabolite concentrations). Therefore, the application of
this method is limited to small-scale metabolic models for only
extremely well-studied organisms [29]. However, the advances on this
method are increasing and significant efforts have been made to build
genome-scale kinetic models [30].
Constraint-based modeling (CBM) can overcome the limitations of the
kinetic models by reducing the need for complex kinetic parameters.
Therefore, this approach has been extensively used for understanding the
behavior of genome-wide systems [31]. The main goal of CBM is to
build models with high prediction accuracy to analyze the genome-scale
networks and shed light on relationships between genotype, phenotype,
and environmental conditions [32, 33]. In this section, we first
summarize the main concepts of CBM and next, we present recent
applications of this method in optimizing the fermentation processes.