title: A global regulatory role of gluconeogenic genes in Escherichia coli revealed by transcriptome network analysis.
abstract: In bacterial adaptation to the dynamic environment, metabolic genes are typically thought to be the executors, whereas global transcription regulators are regarded as the decision makers. Although the feedback from metabolic consequence is believed to be important, much less is understood. This work demonstrates that the gluconeogenic genes in Escherichia coli, ppsA, sfcA, and maeB, provide a feedback loop to the global regulator, cAMP receptor protein (CRP), in carbon source transition. Disruption of one of the gluconeogenic pathways has no phenotype in balanced growth, but causes a significant delay in the diauxic transition from glucose to acetate. To investigate the underlying mechanism, we measured the transcriptome profiles during the transition using DNA microarray, and network component analysis was employed to obtain the transcription factor activities. Results showed that one of the global regulators, CRP, was insufficiently activated during the transition in the ppsA deletion mutant. Indeed, addition of cAMP partially rescued the delay in transition. These results suggest that the gluconeogenic flux to phosphoenolpyruvate is important for full activation of adenylate cyclase through the phosphorylated enzyme IIA(glu) of the phosphotransferase system. Reduction of this flux causes insufficient activation of CRP and a global metabolic deficiency, which exemplifies a significant feedback interaction from metabolism to the a global regulatory system.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, California 90095, USA.
authors.forename: Katy C
authors.initials: KC
authors.lastname: Kao
authors.forename: Linh M
authors.initials: LM
authors.lastname: Tran
authors.forename: James C
authors.initials: JC
authors.lastname: Liao
mesh_terms: D000085:Acetates / Q000737:chemistry / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D002244:Carbon / Q000378:metabolism; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000085:Acetates; D002373:Cyclic AMP Receptor Protein; D017931:DNA Primers; D012333:RNA, Messenger; D014157:Transcription Factors; D010728:Phosphoenolpyruvate; D002244:Carbon; D000242:Cyclic AMP; D010731:Phosphoenolpyruvate Sugar Phosphotransferase System; D000262:Adenylyl Cyclases; D005947:Glucose