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.