ABSTRACTMetabolism consists of biochemical reactions that are combined to generate a robust metabolic network that can respond to perturbations and also adapt to changing environmental conditions.Escherichia coliandSalmonella entericaare closely related enterobacteria that share metabolic components, pathway structures, and regulatory strategies. The synthesis of thiamine inS. entericahas been used to define a node of the metabolic network by analyzing alternative inputs to thiamine synthesis from diverse metabolic pathways. To assess the conservation of metabolic networks in organisms with highly conserved components, metabolic contributions to thiamine synthesis inE. coliwere investigated. Unexpectedly, we found that, unlikeS. enterica,E. colidoes not use the phosphoribosylpyrophosphate (PRPP) amidotransferase (PurF) as the primary enzyme for synthesis of phosphoribosylamine (PRA).In fact, our data showed that up to 50% of the PRA used byE. colito make thiamine requires the activities of threonine dehydratase (IlvA) and anthranilate synthase component II (TrpD). Significantly, the IlvA- and TrpD-dependent pathway to PRA functions inS. entericaonly in the absence of a functionalreactiveintermediatedeaminase (RidA) enzyme, bringing into focus how these closely related bacteria have distinct metabolic networks.IMPORTANCEIn most bacteria, includingSalmonellastrains andEscherichia coli, synthesis of the pyrimidine moiety of the essential coenzyme, thiamine pyrophosphate (TPP), shares enzymes with the purine biosynthetic pathway. Phosphoribosylpyrophosphate amidotransferase, encoded by thepurFgene, generates phosphoribosylamine (PRA) and is considered the first enzyme in the biosynthesis of purines and the pyrimidine moiety of TPP. We show here that, unlikeSalmonella,E. colisynthesizes significant thiamine from PRA derived from threonine using enzymes from the isoleucine and tryptophan biosynthetic pathways. These data show that two closely related organisms can have distinct metabolic network structures despite having similar enzyme components, thus emphasizing caveats associated with predicting metabolic potential from genome content.
Simulation of Escherichia coli Dynamics in Biofilms and Submerged Colonies with an Individual-Based Model Including Metabolic Network Information
