S51 Family Peptidases Provide Resistance to Peptidyl-Nucleotide Antibiotic McC

mBio

Eldar Yagmurov¹  Konstantin Gilep¹  Konstantin Severinov¹  Svetlana Dubiley¹  Marina Serebryakova²  Yuri I. Wolf³ 

[1] Center Molecular and Cellular Biology, Skolkovo Institute of Science and Technology, Moscow, Russia;Institute of Gene Biology, Russian Academy of Science, Moscow, Russia;National Center for Biotechnology Information, National Library of Medicine, Bethesda, Maryland, USA;

关键词: RiPPs;    antibiotics;    microcin C;    S1 family peptidases;    peptide-nucleotides;   

DOI  :  10.1128/mbio.00805-22

来源: DOAJ

【 摘 要 】

ABSTRACT Microcin C (McC)-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 by gene clusters responsible for biosynthesis of McC-like compounds, most are encoded by standalone genes whose products may provide a basal level of resistance to peptide-nucleotide antibiotics in phylogenetically distant bacteria. IMPORTANCE Here, 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 a basal level of resistance to an important class of natural antibiotics.

【 授权许可】

Unknown