Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12

Nat Biotechnol. 2009 May;27(5):462-4. doi: 10.1038/nbt.1538. Epub 2009 Apr 26.


We show that selection of drug-resistant bacterial mutants allows the discovery of antibacterial compounds. Mutant strains of a soil-isolated Streptomyces species that does not produce antibacterials synthesize a previously unknown class of antibacterial, which we name piperidamycin. Overall, 6% of non-Streptomyces actinomycetes species and 43% of Streptomyces species that do not produce antibacterials are activated to produce them. The antibacterial-producing mutants all carried mutations in RNA polymerase and/or the ribosomal protein S12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / genetics
  • Actinobacteria / metabolism
  • Anti-Bacterial Agents / analysis*
  • DNA-Directed RNA Polymerases / genetics*
  • Drug Discovery*
  • Mutation*
  • Ribosomal Proteins / genetics*
  • Streptomyces / chemistry*
  • Streptomyces / genetics*
  • Streptomyces / metabolism


  • Anti-Bacterial Agents
  • Ribosomal Proteins
  • ribosomal protein S12
  • DNA-Directed RNA Polymerases