Antimicrobials inspired by nonribosomal peptide synthetase gene clusters

Xavier Vila-Farres, John Chu, Daigo Inoyama, Melinda A. Ternei, Christophe Lemetre, Louis J. Cohen, Wooyoung Cho, Boojala Vijay B. Reddy, Henry A. Zebroski, Joel S. Freundlich, David S. Perlin, Sean F. Brady

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

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.

Original languageEnglish
Pages (from-to)1404-1407
Number of pages4
JournalJournal of the American Chemical Society
Volume139
Issue number4
DOIs
StatePublished - 1 Feb 2017
Externally publishedYes

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