Flux balance analysis of metabolic networks for efficient engineering of microbial cell factories

Metabolic engineering principles have long been applied to explore the metabolic networks of complex microbial cell factories under a variety of environmental constraints for effective deployment of the microorganisms in the optimal production of biochemicals like biofuels, polymers, amino acids, recombinant proteins. One of the methodologies used for analyzing microbial metabolic networks is the Flux Balance Analysis (FBA), which employs applications of optimization techniques for forecasting biomass growth and metabolic flux distribution of industrially important products under specified environmental conditions. The in silico flux simulations are instrumental for designing the production-specific microbial cell factories. However, FBA has some inherent limitations. The present review emphasizes how the incorporation of additional kinetic, thermodynamic, expression and regulatory constraints and integration of omics data into the classical FBA platform improve the prediction accuracy of FBA. A programmed comparison of the simulated data with the experimental observations is presented for supporting the claim. The review further accounts for the successful implementation of classical FBA in biotechnological applications and identifies areas in which classical FBA fails to make correct predictions. The analysis of the predictive capabilities of the different FBA strategies presented here is expected to help researchers in finding new avenues in engineering highly efficient microbial metabolic pathways and identify the key metabolic bottlenecks during the process. Based on the appropriate metabolic network design, fermentation engineers will be able to effectively design the bioreactors and optimize large-scale biochemical production through suitable pathway modifications.