Formation of D-tyrosyl-tRNATyr accounts for the toxicity of D-tyrosine toward Escherichia coli

D-Tyr-tRNA(Tyr) deacylase cleaves the ester bond between a tRNA molecule and a D-amino acid. In Escherichia coli, inactivation of the gene (dtd) encoding this deacylase increases the toxicity of several D-amino acids including D-tyrosine, D-tryptophan, and D-aspartic acid. Here, we demonstrate that, in a Deltadtd cell grown in the presence of 2.4 mM D-tyrosine, similar to40% of the total tRNA(Tyr) pool is converted into D-Tyr-tRNA(Tyr). No D-Tyr-tRNA(Tyr) is observed in dtd(+) cells. In addition, we observe that overproduction of tRNA(Tyr), tRNA(Trp), or tRNA(Asp) protects a Deltadtd mutant strain against the toxic effect of D-tyrosine, D-tryptophan, or D-aspartic acid, respectively. In the case of D-tyrosine, we show that the protection is accounted for by an increase in the concentration of L-Tyr-tRNA(Tyr) proportional to that of overproduced tRNA(Tyr). Altogether, these results indicate that, by accumulating in vivo, high amounts of D-Tyr-tRNA(Tyr) cause a starvation for L-Tyr-tRNA(Tyr). The deacylase prevents the starvation by hydrolyzing D-Tyr-tRNA(Tyr). Overproduction of tRNA(Tyr) also relieves the starvation by increasing the amount of cellular L-Tyr-tRNA(Tyr) available for translation.