An 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 °C. In the presence of isoleucine and valine, the growth rate of the mutant at 37 °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 °C or to anaerobiosis makes the mutant auxotrophic for L-serine. Three double mutants carrying and another known mutation, acquire new auxotrophies: , lacking the stringent response to amino acid limitation, requires leucine; with numerous metabolic perturbations and antibiotic resistances, requires serine and leucine; and , lacking pyridine nucleotide transhydrogenase, requires glutamate or aspartate (or the corresponding amides). The 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


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