Tetarimycin A, an MRSA-active antibiotic identified through induced expression of environmental DNA gene clusters

J Am Chem Soc. 2012 Dec 5;134(48):19552-5. doi: 10.1021/ja3093828. Epub 2012 Nov 27.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Base Sequence
  • Cloning, Molecular
  • Methicillin-Resistant Staphylococcus aureus*
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Sequence Data
  • Multigene Family* / physiology
  • Phylogeny
  • Polycyclic Compounds / chemistry*
  • Polycyclic Compounds / pharmacology
  • Staphylococcus aureus / genetics


  • Anti-Bacterial Agents
  • Polycyclic Compounds
  • tetarimycin A