RRC ID 4976
Author Nakahigashi K, Toya Y, Ishii N, Soga T, Hasegawa M, Watanabe H, Takai Y, Honma M, Mori H, Tomita M.
Title Systematic phenome analysis of Escherichia coli multiple-knockout mutants reveals hidden reactions in central carbon metabolism.
Journal Mol Syst Biol
Abstract Central carbon metabolism is a basic and exhaustively analyzed pathway. However, the intrinsic robustness of the pathway might still conceal uncharacterized reactions. To test this hypothesis, we constructed systematic multiple-knockout mutants involved in central carbon catabolism in Escherichia coli and tested their growth under 12 different nutrient conditions. Differences between in silico predictions and experimental growth indicated that unreported reactions existed within this extensively analyzed metabolic network. These putative reactions were then confirmed by metabolome analysis and in vitro enzymatic assays. Novel reactions regarding the breakdown of sedoheptulose-7-phosphate to erythrose-4-phosphate and dihydroxyacetone phosphate were observed in transaldolase-deficient mutants, without any noticeable changes in gene expression. These reactions, triggered by an accumulation of sedoheptulose-7-phosphate, were catalyzed by the universally conserved glycolytic enzymes ATP-dependent phosphofructokinase and aldolase. The emergence of an alternative pathway not requiring any changes in gene expression, but rather relying on the accumulation of an intermediate metabolite may be a novel mechanism mediating the robustness of these metabolic networks.
Volume 5
Pages 306
Published 2009-1-1
DOI 10.1038/msb.2009.65
PII msb200965
PMID 19756045
PMC PMC2758719
MeSH Carbon / metabolism* Computer Simulation Culture Media / chemistry Culture Media / metabolism Dihydroxyacetone Phosphate / metabolism Escherichia coli / genetics* Escherichia coli / growth & development Escherichia coli / metabolism* Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism Gene Expression Profiling Gene Knockout Techniques / methods* Metabolic Networks and Pathways / genetics Metabolome Models, Biological Mutation Phenotype Sugar Phosphates / metabolism Systems Biology / methods* Transaldolase / metabolism
IF 9.8
Times Cited 94
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
Prokaryotes E. coli ME9062(BW25113) JE5530