Discovery of MRSA active antibiotics using primary sequence from the human microbiome
Journal
Nature Chemical Biology
Journal Volume
12
Journal Issue
12
Pages
1004-1006
Date Issued
2016
Author(s)
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.
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.
SDGs
Type
journal article