Modeling Enzymatic Regulation in Metabolic Networks
Year: 2011
Type: other
Abstract: Metabolic network modeling is a fundamental aspect of systems biology for metabolic engineering applications. Constraint-based modeling has become the most popular framework for modeling metabolic networks at the genome scale, due to its simple formulation. However, the price to pay for this simplicity is the neglection of the enzymatic mechanisms and their kinetic behavior. In order to overcome these limitations, a new generation of kinetic models built from constraint-based models and approximative kinetic formats is emerging. We identify the lack of representation for enzymatic regulation mechanisms as a major limitation in this new approach and propose the utilization of Extended Petri nets as a better scaffold for the creation of kinetic reconstructions that account for this kind regulation. We evaluate the impact of accounting for enzymatic regulation in the central carbon metabolism of E. coli for the simulation of the steady-state phenotype of mutant strains. The work shows evidence that enzymatic regulation influences the mutant phenotype and its representation can improve rational strain design methods.
Authors: Clara Machado, Rafael S. Costa, E. C. Ferreira, Bruce Tidor, Isabel Rocha
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2122338500