From gene expression to metabolic fluxes

The development of genome-wide high-throughput technologies to identify and map cellular components and to quantify different types of cellular molecules has offered new possibilities for the study of biological systems. In the field of metabolic engineering, which deals with the rational redirection of metabolic fluxes toward a product of interest through the introduction of targeted genetic modifications, it is of interest to have tools and models that relate genotype and phenotype. Here, we illustrate how systems biology approaches are being used in metabolic engineering to explore properties and capabilities of microbial cells, to uncover hidden regulatory mechanisms, and to design enhanced microbial cell factories. Several omics technologies that are particularly useful for metabolic engineering are described, including methods for quantification of mRNA levels, metabolite concentrations, and fluxes through reactions. Furthermore, we review classical and integrative methods for analysis of omics data and describe several mathematical models used to predict phenotypic behavior based on the metabolic network structure. Because metabolic networks and metabolic fluxes are at the core of metabolic engineering, a brief introduction to the characteristics of genome-scale metabolic networks and to key aspects of regulation and control of metabolic fluxes are also referred.