EFFECT OF SLOW GROWTH ON METABOLISM OF ESCHERICHIA-COLI, AS REVEALED BY GLOBAL METABOLITE POOL (METABOLOME) ANALYSIS

Escherichia coli growing on glucose in minimal medium controls its met abolite pools in response to environmental conditions. The extent of p ool changes was followed through two-dimensional thin-layer chromatogr aphy of all C-14-glucose labelled compounds extracted from bacteria. T he patterns of metabolites and spot intensities detected by phosphorim aging were found to reproducibly differ depending on culture condition s. Clear trends were apparent in the pool sizes of several of the 70 m ost abundant metabolites extracted from bacteria growing in glucose-li mited chemostats at different growth rates. The pools of glutamate, as partate, trehalose, and adenosine as well as UDP-sugars and putrescine changed markedly. The data on pools observed by two-dimensional thin- layer chromatography were confirmed for amino acids by independent ana lysis. Other unidentified metabolites also displayed different spot in tensities under various conditions, with four trend patterns depending on growth rate. As RpoS controls a number of metabolic genes in respo nse to nutrient limitation, an rpoS mutant was also analyzed for metab olite pools. The mutant had altered metabolite profiles, but only some of the changes at slow growth rates were ascribable to the known cont rol of metabolic genes by RpoS. These results indicate that total meta bolite pool (''metabolome'') analysis offers a means of revealing nove l aspects of cellular metabolism and global regulation.