-
- Shaun W. Lee
- *Department of Pharmacology,
-
- Douglas A. Mitchell
- *Department of Pharmacology,
-
- Andrew L. Markley
- Department of Chemistry and Biochemistry,
-
- Mary E. Hensler
- Skaggs School of Pharmacy and Pharmaceutical Sciences, and
-
- David Gonzalez
- Department of Chemistry and Biochemistry,
-
- Aaron Wohlrab
- Department of Chemistry and Biochemistry,
-
- Pieter C. Dorrestein
- *Department of Pharmacology,
-
- Victor Nizet
- Skaggs School of Pharmacy and Pharmaceutical Sciences, and
-
- Jack E. Dixon
- *Department of Pharmacology,
書誌事項
- 公開日
- 2008-04-15
- DOI
-
- 10.1073/pnas.0801338105
- 公開者
- Proceedings of the National Academy of Sciences
この論文をさがす
説明
<jats:p> Bacteriocins represent a large family of ribosomally produced peptide antibiotics. Here we describe the discovery of a widely conserved biosynthetic gene cluster for the synthesis of thiazole and oxazole heterocycles on ribosomally produced peptides. These clusters encode a toxin precursor and all necessary proteins for toxin maturation and export. Using the toxin precursor peptide and heterocycle-forming synthetase proteins from the human pathogen <jats:italic>Streptococcus pyogenes</jats:italic> , we demonstrate the <jats:italic>in vitro</jats:italic> reconstitution of streptolysin S activity. We provide evidence that the synthetase enzymes, as predicted from our bioinformatics analysis, introduce heterocycles onto precursor peptides, thereby providing molecular insight into the chemical structure of streptolysin S. Furthermore, our studies reveal that the synthetase exhibits relaxed substrate specificity and modifies toxin precursors from both related and distant species. Given our findings, it is likely that the discovery of similar peptidic toxins will rapidly expand to existing and emerging genomes. </jats:p>
収録刊行物
-
- Proceedings of the National Academy of Sciences
-
Proceedings of the National Academy of Sciences 105 (15), 5879-5884, 2008-04-15
Proceedings of the National Academy of Sciences