| Literature DB >> 28055186 |
Xavier Vila-Farres1,2, John Chu1,2, Daigo Inoyama1,2, Melinda A Ternei1,2, Christophe Lemetre1,2, Louis J Cohen1,2, Wooyoung Cho1,2, Boojala Vijay B Reddy1,2, Henry A Zebroski1,2, Joel S Freundlich1,2, David S Perlin1,2, Sean F Brady1,2.
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.Entities:
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Year: 2017 PMID： 28055186 PMCID： PMC7163397 DOI： 10.1021/jacs.6b11861
Source DB: PubMed Journal: J Am Chem Soc ISSN： 0002-7863 Impact factor: 15.419