Optimization of Productivity and Thermodynamic Performance of Metabolic Pathways

Abstract

In this contribution, a novel optimisation strategy has been presented that combines the metabolic flux analysis and pathway identification with the thermodynamic analysis of cellular metabolic systems. First, an optimal metabolic flux distribution among elementary pathways is identified by LP optimisation subject to constraints on flux balance analysis, pathway analysis and negative Gibbs free energy change for pathways, for achieving the maximum yield of products. The Gibbs free energy change for pathways is calculated from the new transformed Gibbs free energy of formation of external metabolites and cofactors that are in stoichiometric balance in metabolic pathways. The consideration of thermodynamic constraints on pathways ensures the selection of feasible pathways. Thereafter, the Gibbs free energy change of pathways is minimised to predict the optimal reaction conditions that facilitate such pathways. Thus the optimisation approach derives the optimal pathway distribution and conditions for the best performance of cellular systems. The effectiveness of the methodology is demonstrated by a case study on the optimisation of pentose phosphate pathway (PPP) and the glycolysis cycle of the insilico Escherichia coli.

Kinetic Modeling Studies of Heterogeneously Catalyzed Biodiesel Synthesis Reactions

“…Raimondeau et al 22 23 and bulk scale mean field (MF) simulations 24 to validate the kinetic parameters estimated using genetic algorithm (GA) based optimization approach. 25,26 The kinetic parameters obtained correspond to the appropriate match between simulation and experimental results of evolution in bulk concentrations.…”

A critical review of integration analysis of microbial electrosynthesis (MES) systems with waste biorefineries for the production of biofuel and chemical from reuse of CO 2

“…Equally, the model that uses reaction controlled charge transfer, the Butler-Volmer equation and has a general basis in non-equilibrium thermodynamics can be applied to smaller dimensions to predict performances of finite elements that can be compiled for up-scaled systems [113]. The analysis of metabolic pathways to expand the source of feedstock, engineer microorganisms and to tune the properties of products [126,127,128,129,130,131] is another thread of research should be explored for optimising MES process design.…”

“…This way the right innovations and options for advanced integration can be supported. Research efforts should be more on the metabolic flux and pathway analyses to reduce the number of experimental trials and optimise the experimental strategy [126,127,128,129,130,131]. It is time to make use of computeraided analytical tools to increase the search efficiency and speed up the commercial uptake of MES technologies, as shown in Fig 12. Finally, the targeted chemicals are listed in Table 2 and the targeted polymers are shown in Fig.…”

Optimization

“…Three optimization problem formulations, a two-step optimization by GAMS, a nondominated sorting genetic algorithm and a MATLAB based combined genetic algorithm and linear programming tool are shown using a cellular system metabolic productivity and thermodynamic performance optimization as an example elsewhere 12,17 . The objective was to deduce optimum flux distributions through a unique set of enzyme-catalyzed pathways for maximizing the production of a given metabolic product of importance.…”