Peptide-nucleotide antibiotic microcin C (McC) is produced by some Escherichia coli strains. Inside a sensitive cell, McC is processed releasing a non-hydrolysable analog of aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. The product of mccE, a gene from plasmid-borne McC biosynthetic cluster, acetylates processed McC converting it into a non-toxic compound. MccE is homologous to chromosomally-encoded acetyltransferases RimI, RimJ, and RimL, which acetylate, correspondingly, N-termini of ribosomal proteins S18, S5, and L12. Here, we show that E. coli RimL, but not other Rim acetyltransferases, provides a basal level of resistance to McC and various toxic non-hydrolysable aminoacyl adenylates. RimL ... More
Peptide-nucleotide antibiotic microcin C (McC) is produced by some Escherichia coli strains. Inside a sensitive cell, McC is processed releasing a non-hydrolysable analog of aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. The product of mccE, a gene from plasmid-borne McC biosynthetic cluster, acetylates processed McC converting it into a non-toxic compound. MccE is homologous to chromosomally-encoded acetyltransferases RimI, RimJ, and RimL, which acetylate, correspondingly, N-termini of ribosomal proteins S18, S5, and L12. Here, we show that E. coli RimL, but not other Rim acetyltransferases, provides a basal level of resistance to McC and various toxic non-hydrolysable aminoacyl adenylates. RimL acts by acetylating processed McC, which, along with ribosomal protein L12, should be considered as natural RimL substrate. When overproduced, RimL also makes cells resistant to albomycin, an antibiotic which upon intracellular processing gives rise to a seryl-thioribosyl pyrimidine that targets seryl-tRNA synthetase. We further show that E. coli YhhY, a protein related to Rim acetyltransferases but without a known function, is also able to detoxify several non-hydrolysable aminoacyl adenylates but not processed McC. We propose that RimL and YhhY protect bacteria from various toxic aminoacyl nucleotides, either exogenous or those generated inside the cell during normal metabolism.
