A genome-scale metabolic reconstruction consists of a large set of linear algebraic equations with the equations representing stoichiometric mass balances on the intracellular metabolites and the variables representing the unknown reaction fluxes. Because the number of unknowns invariably exceeds the number of equations, the fluxes are typically calculated using flux balance analysis (FBA) with an assumed cellular objective of growth rate maximization. FBA is the most commonly used of the constraint-based methods, which employ linear programming to determine optimal fluxes subject to a set of flux constraints (e.g., lower and upper bounds). In Silico Fermentation offers substantial expertise in the development and application of constraint-based methods for the analysis and optimization of microbial metabolism
Flux Balance Analysis
The basic steps in applying FBA to a genome-scale model are to define the nutrient uptake bounds, define the cellular objective function, perform FBA, and analyze the results which consist of a vector of all the predicted reaction fluxes. We have substantial expertise deriving nutrient uptake bounds that generate reasonable in silico growth rates and analyzing FBA results with respect to key pathway fluxes and product secretion rates. Our MATLAB app mediumFBA automates the FBA workflow assuming a maximal growth objective, which is the default encoded in most models. We can use a combination of mediumFBA simulations and customized MATLAB codes to conduct any FBA study of interest.
Other Constraint-Based Methods
We have considerable experience with other constraint-based analysis methods provided in the MATLAB constraint-based reconstruction and analysis (COBRA) toolbox, including parsimonious FBA, minimization of metabolic adjustment (MOMA), and flux variability analysis (FVA). Because the FBA linear programming formulation can return non-unique flux solutions, FVA is a particularly valuable for calculating the possible range of each flux across all possible optimal flux solutions. Our mediumFBA app returns both FBA and FVA solutions to provide more complete characterization of flux solutions. We also offer unique capabilities for performing dynamic FBA calculations as detailed for our expertise in bioreactor process simulation.
Please contact us to discuss your metabolic model simulation and analysis needs.
