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


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 ?-lactam activity against methicillin-resistant Staphylococcus aureus in mice, potentially providing a new treatment regimen.

SUBMITTER: Chu J 

PROVIDER: S-EPMC5117632 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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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 a  ...[more]

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