Antimicrobials inspired by nonribosomal peptide synthetase gene clusters
Journal
Journal of the American Chemical Society
Journal Volume
139
Journal Issue
4
Pages
1404-1407
Date Issued
2017
Author(s)
Vila-Farres, X.
Inoyama, D.
Ternei, M.A.
Lemetre, C.
Cohen, L.J.
Cho, W.
Reddy, B.V.B.
Zebroski, H.A.
Freundlich, J.S.
Perlin, D.S.
Brady, S.F.
Abstract
Bacterial culture broth extracts have been the starting point for the development of numerous therapeutics. However, only a small fraction of bacterial biosynthetic diversity is accessible using this strategy. Here, we apply a discovery approach that bypasses the culturing step entirely by bioinformatically predicting small molecule structures from the primary sequences of the biosynthetic gene clusters. These structures are then chemically synthesized to give synthetic-bioinformatic natural products (syn-BNPs). Using this approach, we screened syn-BNPs inspired by nonribosomal peptide synthetases against microbial pathogens, and discovered an antibiotic for which no resistance could be identified and an antifungal agent with activity against diverse fungal pathogens.
SDGs
Type
journal article