MccE Provides resistance to protein synthesis inhibitor microcin C by acetylating the processed form of the antibiotic

Maria Novikova, Teymur Kazakov, Gaston H. Vondenhoff, Ekaterina Semenova, Jef Rozenski, Anastasija Metlytskaya, Inna Zukher, Anton Tikhonov, Arthur Van Aerschot, Konstantin Severinov

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The heptapeptide-nucleotide microcin C (McC) is a potent inhibitor of enteric bacteria growth. McC is excreted from producing cells by the MccC transporter. The residual McC that remainsin the producing cell can be processed by cellular amino-peptidases with the release of a non-hydrolyzable aspartyl-adenylate, a strong inhibitor of aspartyl-tRNA synthetase. Accumulation of processed McC inside producing cells should therefore lead to translation inhibition and cessation of growth. Here, we show that a product of another gene of the McC biosynthetic cluster, mccE, acetylates processed McC and converts it into a non-toxic compound. MccE also makes Escherichia coli resistant to albomycin, a Trojan horse inhibitor unrelated to McC that, upon processing, gives rise to a serine coupled to a thioxylofuranosyl pyrimidine, an inhibitor of seryl-tRNA synthetase. We speculate that MccE and related cellular acetyl-transferases of the Rim family may detoxify various aminoacyl- nucleotides, either exogenous or those generated inside the cell.

Original languageEnglish (US)
Pages (from-to)12662-12669
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number17
DOIs
StatePublished - Apr 23 2010

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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