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Tetarimycin A, an MRSA-active antibiotic identified through induced expression of environmental DNA gene clusters.
- Source :
-
Journal of the American Chemical Society [J Am Chem Soc] 2012 Dec 05; Vol. 134 (48), pp. 19552-5. Date of Electronic Publication: 2012 Nov 27. - Publication Year :
- 2012
-
Abstract
- The propagation of DNA extracted directly from environmental samples in laboratory-grown bacteria provides a means to study natural products encoded in the genomes of uncultured bacteria. However, gene silencing often hampers the functional characterization of gene clusters captured on environmental DNA clones. Here we show that the overexpression of transcription factors found in sequenced environmental DNA-derived biosynthetic gene clusters, in conjunction with traditional culture-broth extract screening, can be used to identify new bioactive secondary metabolites from otherwise-silent gene clusters. Tetarimycin A, a tetracyclic methicillin-resistant Staphylococcus aureus (MRSA)-active antibiotic, was isolated from the culture-broth extract of Streptomyces albus cultures cotransformed with an environmentally derived type-II polyketide biosynthetic gene cluster and its pathway-specific Streptomyces antibiotic regulatory protein (SARP) cloned under the control of the constitutive ermE* promoter.
- Subjects :
- Anti-Bacterial Agents chemistry
Anti-Bacterial Agents pharmacology
Bacteria drug effects
Base Sequence
Cloning, Molecular
Microbial Sensitivity Tests
Models, Molecular
Molecular Sequence Data
Phylogeny
Polycyclic Compounds pharmacology
Staphylococcus aureus genetics
Methicillin-Resistant Staphylococcus aureus
Multigene Family physiology
Polycyclic Compounds chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-5126
- Volume :
- 134
- Issue :
- 48
- Database :
- MEDLINE
- Journal :
- Journal of the American Chemical Society
- Publication Type :
- Academic Journal
- Accession number :
- 23157252
- Full Text :
- https://doi.org/10.1021/ja3093828