Eldar Yagmurov (deceased), Konstantin Gilep, Svetlana Dubiley and Konstantin Severinov published a preprint “S51 family peptidases provide resistance to peptidyl-nucleotide antibiotic McC” at bioRxiv. Microcin C-like compounds (McC) are natural peptide-nucleotide antibiotics produced by diverse bacteria. In bacterial cell, the peptide part is degraded, releasing the toxic payload, an isoaspartyl-nucleotide that inhibits aspartyl-tRNA synthetase, an enzyme essential for protein synthesis. The researchers have described a novel pathway developed by bacteria to avoid self-intoxication. The pathway involves S51 family peptidases, which was named as MccG by the authors of the preprint. MccG cleaves the toxic isoaspartyl-nucleotide rendering it inactive. While some MccG homologs are encoded in gene clusters responsible for McC-like compounds biosynthesis, most are encoded by stand-alone genes. The products of these genes may provide basal level of resistance to peptide-nucleotide antibiotics in phylogenetically distant bacteria. Full text of the preprint is available here.