Metabolic Engineering: Flux Balance Analysis
(2006)metabolic networks, flux balance analysis, steady states, elementary modes & extreme pathways, linear programming.Abstract
Biologists are interested in the capabilities of metabolic networks. A number of mathematical and
biological models were developed to predict these capabilities based on stoichiometric and kinetic
information. The predicted outcomes can help to create new hypotheses which can be tested and
used within metabolic engineering to optimize certain pathways in an organism.
Three models will be explained and discussed in this paper. Metabolic control analysis will predict
single solutions, but requires lots of information about the parameters of the enzymes in the organism.
This will form a drawback of the method, because a lot of this kinetic information is not yet available.
The second approach, carbon flux analysis is a combined mathematical/biological approach based on
modified carbon molecules which are fed to the organism. Based on measuring where these
molecules are located, predictions can be made about the fluxes within the model. The third model,
flux balance analysis, will be discussed in more detail.
Flux balance analysis is a constraints-based approach. This model will not create a single prediction,
but instead it will create a solution space based on stoichiometric information. The solution space can
then be reduced by biochemical and environmental constraints. Based on an objective function,
optimalization can be applied to find the flux distribution which optimizes this objective function.
Adding gene regulation to the model will further reduce the solution space and can even help predict
outcomes under different conditions. This second generation of flux balance models can open new
doors by adding more additional information about the organism and further reducing the solution
space.