The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA 
synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid 
selectivity is compromised, fidelity can be ensured by an inherent AARS editing 
activity that hydrolyses mischarged tRNAs. Here, we show that the editing 
activity of Escherichia coli leucyl-tRNA synthetase (EcLeuRS) is not required to 
prevent incorrect isoleucine incorporation. Rather, as shown by kinetic, 
structural and in vivo approaches, the prime biological function of LeuRS 
editing is to prevent mis-incorporation of the non-standard amino acid 
norvaline. This conclusion follows from a reassessment of the discriminatory 
power of LeuRS against isoleucine and the demonstration that a LeuRS 
editing-deficient E. coli strain grows normally in high concentrations of 
isoleucine but not under oxygen deprivation conditions when norvaline 
accumulates to substantial levels. Thus, AARS-based translational quality 
control is a key feature for bacterial adaptive response to oxygen deprivation. 
The non-essential role for editing under normal bacterial growth has important 
implications for the development of resistance to antimicrobial agents targeting 
the LeuRS editing site.