The emergence of systems biology has re-emphasized the advantages of understanding biological processes with a global perspective. One biological process amenable to global approaches is microbial metabolism. This review describes a model system that contributes to the goals of systems biology by experimentally defining metabolic integration found in a bacterial cell and thus providing data needed for implementation and interpretation of systems approaches. We have taken a largely unbiased in vivo approach centered on thiamine biosynthesis to identify new metabolic components and connections, and to explore uncharacterized paradigms of the integration between them. This article summarizes recent results from this approach that include the identification of the function of unknown genes, connections between cofactors biosynthesis and thiamine biosynthesis, and how metabolites from one biosynthetic pathway can be used in thiamine biosynthesis.
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