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

Chu John J Vila-Farres Xavier X Inoyama Daigo D Ternei Melinda M Cohen Louis J LJ Gordon Emma A EA Reddy Boojala Vijay B BV Charlop-Powers Zachary Z Zebroski Henry A HA Gallardo-Macias Ricardo R Jaskowski Mark M Satish Shruthi S Park Steven S Perlin David S DS Freundlich Joel S JS Brady Sean F SF

Nature chemical biology 20161017 12

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]

PMID: 27748750

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