TY - JOUR TI - A single transcription factor regulates evolutionarily diverse but functionally linked metabolic pathways in response to nutrient availability. AU - Schmid, Amy K. AU - Reiss, David J. AU - Pan, Min AU - Koide, Tie AU - Baliga, Nitin S. T2 - Molecular systems biology AB - During evolution, enzyme-coding genes are acquired and/or replaced through lateral gene transfer and compiled into metabolic pathways. Gene regulatory networks evolve to fine tune biochemical fluxes through such metabolic pathways, enabling organisms to acclimate to nutrient fluctuations in a competitive environment. Here, we demonstrate that a single TrmB family transcription factor in Halobacterium salinarum NRC-1 globally coordinates functionally linked enzymes of diverse phylogeny in response to changes in carbon source availability. Specifically, during nutritional limitation, TrmB binds a cis-regulatory element to activate or repress 113 promoters of genes encoding enzymes in diverse metabolic pathways. By this mechanism, TrmB coordinates the expression of glycolysis, TCA cycle, and amino-acid biosynthesis pathways with the biosynthesis of their cognate cofactors (e.g. purine and thiamine). Notably, the TrmB-regulated metabolic network includes enzyme-coding genes that are uniquely archaeal as well as those that are conserved across all three domains of life. Simultaneous analysis of metabolic and gene regulatory network architectures suggests an ongoing process of co-evolution in which TrmB integrates the expression of metabolic enzyme-coding genes of diverse origins. DA - 2009/// PY - 2009 DO - 10.1038/msb.2009.40 VL - 5 SP - 282 J2 - Mol Syst Biol LA - eng SN - 1744-4292 1744-4292 KW - Amino Acid Sequence KW - Archaeal Proteins/*genetics/metabolism KW - Binding Sites KW - Carbohydrate Metabolism KW - Databases, Genetic KW - Enhancer Elements, Genetic KW - Evolution, Molecular KW - Gene Expression Profiling KW - Halobacterium salinarum/*genetics/metabolism KW - Metabolic Networks and Pathways/*genetics/physiology KW - Molecular Sequence Data KW - Oxidation-Reduction KW - Phenotype KW - Promoter Regions, Genetic KW - Sequence Alignment KW - Sequence Analysis, Protein KW - Signal Transduction/genetics/physiology KW - Stress, Physiological KW - Transcription Factors/*genetics/metabolism KW - gene regulatory networks ER -