Increased mutation frequency in redox-impaired Escherichia coli due to RelA- and RpoS-mediated repression of DNA repair.

ABSTRACT: Balancing of reducing equivalents is a fundamental issue in bacterial metabolism and metabolic engineering. Mutations in the key metabolic genes ldhA and pflB of Escherichia coli are known to stall anaerobic growth and fermentation due to a buildup of intracellular NADH. We observed that the rate of spontaneous mutation in E. coli BW25113 (DeltaldhA DeltapflB) was an order of magnitude higher than that in wild-type (WT) E. coli BW25113. We hypothesized that the increased mutation frequency was due to an increased NADH/NAD(+) ratio in this strain. Using several redox-impaired strains of E. coli and different redox conditions, we confirmed a significant correlation (P < 0.01) between intracellular-NADH/NAD(+) ratio and mutation frequency. To identify the genetic basis for this relationship,

SUBMITTER: Singh A 

PROVIDER: S-EPMC2918982 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature