title: Large-scale 13C-flux analysis reveals distinct transcriptional control of respiratory and fermentative metabolism in Escherichia coli.
abstract: Despite our increasing topological knowledge on regulation networks in model bacteria, it is largely unknown which of the many co-occurring regulatory events actually control metabolic function and the distribution of intracellular fluxes. Here, we unravel condition-dependent transcriptional control of Escherichia coli metabolism by large-scale (13)C-flux analysis in 91 transcriptional regulator mutants on glucose and galactose. In contrast to the canonical respiro-fermentative glucose metabolism, fully respiratory galactose metabolism depends exclusively on the phosphoenol-pyruvate (PEP)-glyoxylate cycle. While 2/3 of the regulators directly or indirectly affected absolute flux rates, the partitioning between different pathways remained largely stable with transcriptional control focusing primarily on the acetyl-CoA branch point. Flux distribution control was achieved by nine transcription factors on glucose, including ArcA, Fur, PdhR, IHF A and IHF B, but was exclusively mediated by the cAMP-dependent Crp regulation of the PEP-glyoxylate cycle flux on galactose. Five further transcription factors affected this flux only indirectly through cAMP and Crp by increasing the galactose uptake rate. Thus, E. coli actively limits its galactose catabolism at the expense of otherwise possible faster growth.
authors: Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
authors: Bart R B
authors: BR
authors: Haverkorn van Rijsewijk
authors: Annik
authors: A
authors: Nanchen
authors: Sophie
authors: S
authors: Nallet
authors: Roelco J
authors: RJ
authors: Kleijn
authors: Uwe
authors: U
authors: Sauer
mesh_terms: D000105:Acetyl Coenzyme A / Q000378:metabolism*; D002244:Carbon / Q000378:metabolism*; D002247:Carbon Isotopes / Q000378:metabolism; D002952:Citric Acid Cycle; D000242:Cyclic AMP / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005690:Galactose / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D006038:Glyoxylates / Q000378:metabolism; D007553:Isotope Labeling; D010100:Oxygen / Q000378:metabolism; D010728:Phosphoenolpyruvate / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002247:Carbon Isotopes; D029968:Escherichia coli Proteins; D006038:Glyoxylates; D014157:Transcription Factors; D000105:Acetyl Coenzyme A; D010728:Phosphoenolpyruvate; D002244:Carbon; D000242:Cyclic AMP; D005947:Glucose; C031150:glyoxylic acid; D010100:Oxygen; D005690:Galactose