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Nat Chem Biol. 2016 Dec;12(12):1004-1006. doi: 10.1038/nchembio.2207. Epub 2016 Oct 17.

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

Author information

1
Laboratory of Genetically Encoded Small Molecules, The Rockefeller University, New York, New York, USA.
2
Department of Pharmacology, Physiology, and Neuroscience, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.
3
Proteomics Resource Center, The Rockefeller University, New York, New York, USA.
4
Public Health Research Institute, Rutgers University-New Jersey Medical School, Newark, New Jersey, USA.

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.

PMID:
27748750
PMCID:
PMC5117632
DOI:
10.1038/nchembio.2207
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Financial Interest Statement The authors declare no competing financial interests.

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