2. Academic Validation
  3. Discovery of MRSA active antibiotics using primary sequence from the human microbiome

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

  • Nat Chem Biol. 2016 Dec;12(12):1004-1006. doi: 10.1038/nchembio.2207.
John Chu 1,  Xavier Vila-Farres 1,  Daigo Inoyama 2,  Melinda Ternei 1,  Louis J Cohen 1,  Emma A Gordon 1,  Boojala Vijay B Reddy 1,  Zachary Charlop-Powers 1,  Henry A Zebroski 3,  Ricardo Gallardo-Macias 2,  Mark Jaskowski 2,  Shruthi Satish 2,  Steven Park 4,  David S Perlin 4,  Joel S Freundlich 2,  Sean F Brady 1
Affiliations

Affiliations

  • 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.
PMID: 27748750 DOI: 10.1038/nchembio.2207
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.

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