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

John Chu, Xavier Vila-Farres, Daigo Inoyama, Melinda Ternei, Louis J. Cohen, Emma A. Gordon, Boojala Vijay B. Reddy, Zachary Charlop-Powers, Henry A. Zebroski, Ricardo Gallardo-Macias, Mark Jaskowski, Shruthi Satish, Steven Park, David S. Perlin, Joel S. Freundlich, Sean F. Brady

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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 we applied the approach 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.

Original languageEnglish (US)
Pages (from-to)1004-1006
Number of pages3
JournalNature Chemical Biology
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2016
Externally publishedYes

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    Chu, J., Vila-Farres, X., Inoyama, D., Ternei, M., Cohen, L. J., Gordon, E. A., Reddy, B. V. B., Charlop-Powers, Z., Zebroski, H. A., Gallardo-Macias, R., Jaskowski, M., Satish, S., Park, S., Perlin, D. S., Freundlich, J. S., & Brady, S. F. (2016). Discovery of MRSA active antibiotics using primary sequence from the human microbiome. Nature Chemical Biology, 12(12), 1004-1006. https://doi.org/10.1038/nchembio.2207