ABSTRACT
The antibiotic borrelidin, which has been shown to inhibit threonyl–tRNA synthetase (ThrRS) from Escherichia coli and yeast, also proved to be highly toxic to Chinese hamster ovary cells. The percentage of the total soluble cellular protein represented by ThrRS in these most highly resistant cell lines is well what has been achieved in a variety of other systems. Cell lines cloned from populations resistant to various concentrations of borrelidin have been cultured for hundreds of generations in the absence of the drug with no resulting loss of resistance or decrease in ThrRS activity. The complete sequence of a human ThrRS cDNA has been determined and the amino acid sequence deduced. Borrelidin is a highly specific inhibitor of ThrRS and kills cells by preventing protein synthesis. When cells are exposed to increasing concentrations of the drug in a stepwise manner, amplification of the structural gene for ThrRS occurs.
