From the Cover: Discovery of a widely distributed toxin biosynthetic gene cluster Export

@article{citeulike:2676348, abstract = {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 Streptococcus pyogenes, we demonstrate the in vitro 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. 10.1073/pnas.0801338105}, author = {Lee, Shaun W. and Mitchell, Douglas A. and Markley, Andrew L. and Hensler, Mary E. and Gonzalez, David and Wohlrab, Aaron and Dorrestein, Pieter C. and Nizet, Victor and Dixon, Jack E.}, citeulike-article-id = {2676348}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.0801338105}, citeulike-linkout-1 = {http://www.pnas.org/cgi/content/abstract/105/15/5879}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18375757}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18375757}, day = {15}, doi = {10.1073/pnas.0801338105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {antibiotic, pnas}, month = {April}, number = {15}, pages = {5879--5884}, posted-at = {2008-04-16 08:46:36}, priority = {2}, title = {From the Cover: Discovery of a widely distributed toxin biosynthetic gene cluster}, url = {http://dx.doi.org/10.1073/pnas.0801338105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:2676348 L3 - citeulike-article-id:2676348 N2 - 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 Streptococcus pyogenes, we demonstrate the in vitro 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. 10.1073/pnas.0801338105 IS - 15 JF - Proceedings of the National Academy of Sciences EP - 5884 TI - From the Cover: Discovery of a widely distributed toxin biosynthetic gene cluster VL - 105 SP - 5879 KW - antibiotic KW - pnas AU - Lee, Shaun AU - Mitchell, Douglas AU - Markley, Andrew AU - Hensler, Mary AU - Gonzalez, David AU - Wohlrab, Aaron AU - Dorrestein, Pieter AU - Nizet, Victor AU - Dixon, Jack PY - 2008/04/15/ UR - http://dx.doi.org/10.1073/pnas.0801338105 ER -