ИСТИНА

Aminoacyl-tRNA synthetases (aaRSs) are essential housekeeping enzymes present in all domains of life. Thus, inactivation of any of the twenty aaRSs results in protein synthesis inhibition, growth arrest, and eventual cell death. Bacteria extensively exploit aaRSs as antibiotic targets, producing structurally and biosynthetically diverse compounds. Intriguingly, no group of natural congeners capable of inhibiting different aaRSs is known, suggesting that successful tRNA synthetase-targeting antibiotics evolved independently to fit an individual aaRS type. We have identified a new family of bacterial ribosomally synthesized post-translationally modified peptides (RiPPs), which we have named linear imidazolone-containing peptides (LIPs). We showed that LIPs enter the cytoplasm of the target cell via the conserved YejABEF transporter and are processed by cellular peptidases to release the warhead, which binds at the active center of aaRS. Our bioinformatic analysis shows that LIPs include structurally diverse inhibitors of at least seven different aaRS types.