A Trojan-Horse Peptide-Carboxymethyl-Cytidine Antibiotic from Bacillus amyloliquefaciens
| Autor: | Arthur Van Aerschot, Darya Tsibulskaya, Alexey Kulikovsky, Svetlana Dubiley, Olga Mokina, Manesh Nautiyal, Marina V. Serebryakova, Konstantin Severinov |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cytidine monophosphate Bacillus amyloliquefaciens Stereochemistry 030106 microbiology Aspartate-tRNA Ligase Peptide Biochemistry Catalysis Article 03 medical and health sciences chemistry.chemical_compound Colloid and Surface Chemistry Bacteriocins Enzyme Inhibitors Adenylylation chemistry.chemical_classification biology Molecular Structure Computational Biology Cytidine General Chemistry Microcin biology.organism_classification Anti-Bacterial Agents 030104 developmental biology Enzyme chemistry Cytosine |
| Zdroj: | Journal of the American Chemical Society |
| ISSN: | 1520-5126 5690-1569 |
| Popis: | Microcin C and related antibiotics are Trojan-horse peptide-adenylates. The peptide part is responsible for facilitated transport inside the sensitive cell, where it gets processed to release a toxic warhead—a nonhydrolyzable aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. Adenylation of peptide precursors is carried out by MccB THIF-type NAD/FAD adenylyltransferases. Here, we describe a novel microcin C-like compound from Bacillus amyloliquefaciens. The B. amyloliquefaciens MccB demonstrates an unprecedented ability to attach a terminal cytidine monophosphate to cognate precursor peptide in cellular and cell free systems. The cytosine moiety undergoes an additional modification—carboxymethylation—that is carried out by the C-terminal domain of MccB and the MccS enzyme that produces carboxy-SAM, which serves as a donor of the carboxymethyl group. We show that microcin C-like compounds carrying terminal cytosines are biologically active and target aspartyl-tRNA synthetase, and that the carboxymethyl group prevents resistance that can occur due to modification of the warhead. The results expand the repertoire of known enzymatic modifications of peptides that can be used to obtain new biological activities while avoiding or limiting bacterial resistance. ispartof: Journal of the American Chemical Society vol:138 issue:48 pages:15690-15698 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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