Amycomicin is a potent and specific antibiotic discovered with a targeted interaction screen [electronic resource]

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Tác giả:

Ngôn ngữ: eng

Ký hiệu phân loại: 615.19 Pharmaceutical chemistry

Thông tin xuất bản: Washington, D.C. : Oak Ridge, Tenn. : United States. Dept. of Energy. Office of Science ; Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018

Mô tả vật lý: Size: p. 10124-10129 : , digital, PDF file.

Bộ sưu tập: Metadata

ID: 260153

 The rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated the search for new antibiotics. Many clinically used antibacterials were discovered through culturing a single microbial species under nutrient-rich conditions, but in the environment, bacteria constantly encounter poor nutrient conditions and interact with neighboring microbial species. In an effort to recapitulate this environment, we generated a nine-strain actinomycete community and used 16S rDNA sequencing to deconvolute the stochastic production of antimicrobial activity that was not observed from any of the axenic cultures. We subsequently simplified the community to just two strains and identified <
 em>
 Amycolatopsis<
 /em>
 sp. AA4 as the producing strain and <
 em>
 Streptomyces coelicolor<
 /em>
  M145 as an inducing strain. Bioassay-guided isolation identified amycomicin (AMY), a highly modified fatty acid containing an epoxide isonitrile warhead as a potent and specific inhibitor of <
 em>
 Staphylococcus aureus<
 /em>
 . Amycomicin targets an essential enzyme (FabH) in fatty acid biosynthesis and reduces <
 em>
 S. aureus<
 /em>
  infection in a mouse skin-infection model. The discovery of AMY demonstrates the utility of screening complex communities against specific targets to discover small-molecule antibiotics.
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