ALTERED AMINO-ACID-METABOLISM IN LRP MUTANTS OF ESCHERICHIA-COLI K12 AND THEIR DERIVATIVES

An Escherichia coli lrp mutant, lacking the leucine-responsive regulatory protein and the global response it controls, is deregulated in the expression of many genes, but is nevertheless able to grow in glucose-minimal medium at 37 degrees C. In the presence of isoleucine and valine, the growth rate of the lrp mutant at 37 degrees C is significantly increased by exogenous L-serine or L-leucine (or both). suggesting that synthesis of these amino acids is limiting. In the absence of isoleucine and valine, however, growth is severely inhibited by both L-serine and L-leucine. A shift to 42 degrees C or to anaerobiosis makes the lrp mutant auxotrophic for L-serine. Three double mutants carrying lrp and another known mutation, acquire new auxotrophies: lrp relA, lacking the stringent response to amino acid limitation, requires leucine; lrp ssd with numerous metabolic perturbations and antibiotic resistances, requires serine and leucine; and lrp pnt, lacking pyridine nucleotide transhydrogenase, requires glutamate or aspartate (or the corresponding amides). The lrp mutant, although able to achieve balanced growth in some conditions, is clearly on the edge of a metabolic precipice, unable to tolerate many physiological and genetic perturbations which are inocuous to wild-type E. coli.