Optimal re-design of primary metabolism in Escherichia coli using linlog kinetics

Impact of Thermodynamic Principles in Systems Biology

“…In a follow up study [31] a non-linear model of glycolysis in E. coli was successfully approximated using lin-log kinetics and a connected product pathway was successfully redesigned in silico with respect to the required large changes in enzyme activities. Even more interesting was a recent study of Smallbone et al [32] in which they showed that a lin-log kinetic model of glycolysis in Saccharomyces cerevisiae, in which elasticities were assumed equal to their reaction stoichiometric coefficients, gave surprising agreement with the mechanistic Teusink model!!…”

Design of stable metabolic networks

“…Also, an increase in metabolite concentration could inhibit enzyme activity [7,10]. To account for this condition, Eq.…”

“…In this sense, several authors have formulated different problems to determine optimal designs of metabolic networks. Visser et al [10] formulate an optimal design problem to maximize serine production and the flux through the phosphotransferase system in E. coli. Chang and Sahinidis [8] propose solution with a global optimization algorithm, for metabolic network design problem that includes stability constraints through the Routh-Hurwitz criterion and the Vieta theorem.…”

The elucidation of metabolic pathways and their improvements using stable optimization of large-scale kinetic models of cellular systems

“…Random multistarts have been used to check the robustness of the SQP search and no alternative global optima was found as earlier reported by Visser et al (2004). Tight absolute (i.e.…”

“…In response to these limitations and challenges, a number of research groups have undertaken the development of plausible large-scale kinetic models. Prominent modeling projects include large-scale kinetic models of Saccharomyces cerevisiae (Hynne et al 2001;Rizzi et al 1997) and Escherichia coli (Chassagnole et al 2002;Visser et al 2004), the kinetic model of central metabolism coupled with tryptophan gene expression in E.coli , and computer models of single cells capturing dynamic effects of chromosome replication and changes in the cell geometry (Atlas et al, 2008;Castellanos et al 2007;Domach et al 1984;Nikolaev et al 2006). The discussed models are highly nonlinear, stiff and include many kinetic parameters which are hard to identify from the measurements.…”