Formation of D-tyrosyl-tRNATyr accounts for the toxicity of D-tyrosine toward Escherichia coli.
Abstract
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 $\Delta$dtd cell grown in the presence of 2.4 mm D-tyrosine, approximately 40% 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 $\Delta$dtd 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-tRNATyr 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.
Origin : Publisher files allowed on an open archive
