Flux Balance Analysis

Flux Balance Analysis

Flux balance analysis (FBA) is a mathematical method for analyzing metabolism. It is a direct application of linear programming to biological systems that uses the stoichiometric coefficients for each reaction in the system as the set of constraints for the optimization. Additionally, this method requires the assumption of biological steady state, or homeostasis. Imposing this restriction allows the assumption that at any given time the concentration of a given compound in the metabolic network is constant. Then, depending on what is being studied, a specific phenotype will be selected and a relevant biological parameter will be maximized.

One of the main strengths of the flux balance approach is that it does not require any knowledge of the metabolite concentrations, or more importantly, the enzyme kinetics of the system; the homeostasis assumption precludes the need for knowledge of nutrients at any time as long as that quantity remains constant, and additionally it removes the need for specific rate laws since it simply requires that the total flux of any compound in the system is 0. The stoichiometric coefficients alone are sufficient for the mathematical maximization of a specific objective function.

The objective function is essentially a measure of how each component in the system contributes to the production of the desired product. The product itself depends on the purpose of the model, but one of the most common examples is the study of total biomass. A notable example of the success of FBA is the ability to accurately predict the growth rate of the prokaryote E. coli when cultured in different conditions. In this case, the metabolic system was optimized to maximize the biomass objective function. More generally, though, this model can be used to optimize the production of any product, and is often used to determine the output level of some biotechnologically relevant product. The model itself can be experimentally verified by cultivating organisms using a chemostat or similar tools to ensure that nutrient concentrations are held constant. Measurements of the production of the desired objective can then be used to correct the model.

A good description of the basic concepts of FBA can be found in the freely available supplementary material to Edwards et al. 2001 which can be found at the Nature website. Further sources include the book "Systems Biology" by B. Palsson dedicated to the subject and a useful tutorial and paper by J. Orth. Many other sources of information on the technique exist in published scientific literature including Lee et al. 2006, Feist et al. 2008, and Lewis et al. 2012.