{"doi":"10.1101/2022.03.27.485901","title":"S51 family peptidases provide resistance to peptidyl-nucleotide antibiotic McC","abstract":"ABSTRACT Microcin C-like compounds are natural Trojan horse peptide-nucleotide antibiotics produced by diverse bacteria. The ribosomally-synthesized peptide parts of these antibiotics are responsible for their facilitated transport into susceptible cells. Once inside the cell, the peptide part is degraded, releasing the toxic payload, an isoaspartyl-nucleotide that inhibits aspartyl-tRNA synthetase, an enzyme essential for protein synthesis. Bacteria that produce microcin C-like compounds have evolved multiple ways to avoid self-intoxication. Here, we describe a new strategy through the action of S51 family peptidases, which we name MccG. 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 whose products may provide basal level of resistance to peptide-nucleotide antibiotics in phylogenetically distant bacteria. SIGNIFICANCE We identified a natural substrate for a major phylogenetic clade of poorly characterized S51 family proteases from bacteria. We show that these proteins can contribute to basal level of resistance to an important class of natural antibiotics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":306698,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9483,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":919674,"name":"Konstantin Gilep","orcid":"0009-0009-2319-2213","position":1,"is_corresponding":false},{"id":373234,"name":"Marina V. Serebryakova","orcid":"0000-0002-5402-8215","position":2,"is_corresponding":false},{"id":107326,"name":"Yuri I. Wolf","orcid":"0000-0002-0247-8708","position":3,"is_corresponding":false},{"id":373241,"name":"Svetlana Dubiley","orcid":"0000-0001-9225-5534","position":4,"is_corresponding":false},{"id":57617,"name":"Konstantin Severinov","orcid":"0000-0001-9706-450X","position":5,"is_corresponding":false},{"id":513957,"name":"Eldar Yagmurov","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T00:32:52.703737Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}