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Discovery of MRSA active antibiotics using primary sequence from the human microbiome

Here, we present a natural product discovery approach whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When applied to no...

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Detalles Bibliográficos
Autores principales: Chu, John, Vila-Farres, Xavier, Inoyama, Daigo, Ternei, Melinda, Cohen, Louis J., Gordon, Emma A., Reddy, Boojala Vijay B., Charlop-Powers, Zachary, Zebroski, Henry A., Gallardo-Macias, Ricardo, Jaskowski, Mark, Satish, Shruthi, Park, Steven, Perlin, David S., Freundlich, Joel S., Brady, Sean F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5117632/
https://www.ncbi.nlm.nih.gov/pubmed/27748750
http://dx.doi.org/10.1038/nchembio.2207
Descripción
Sumario:Here, we present a natural product discovery approach whereby structures are bioinformatically predicted from primary sequence and produced by chemical synthesis (synthetic-bioinformatic natural products, syn-BNPs), circumventing the need for bacterial culture and gene expression. When applied to nonribosomal peptide synthetase gene clusters from human-associated bacteria we identified the humimycins. These antibiotics inhibit lipid II flippase and potentiate β-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.