Discovery of microbial natural products by activation of silent biosynthetic gene clusters

Nat Rev Microbiol. 2015 Aug;13(8):509-23. doi: 10.1038/nrmicro3496. Epub 2015 Jun 29.


Microorganisms produce a wealth of structurally diverse specialized metabolites with a remarkable range of biological activities and a wide variety of applications in medicine and agriculture, such as the treatment of infectious diseases and cancer, and the prevention of crop damage. Genomics has revealed that many microorganisms have far greater potential to produce specialized metabolites than was thought from classic bioactivity screens; however, realizing this potential has been hampered by the fact that many specialized metabolite biosynthetic gene clusters (BGCs) are not expressed in laboratory cultures. In this Review, we discuss the strategies that have been developed in bacteria and fungi to identify and induce the expression of such silent BGCs, and we briefly summarize methods for the isolation and structural characterization of their metabolic products.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacteria / genetics
  • Bacteria / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biological Products / chemistry
  • Biological Products / metabolism*
  • Gene Expression Regulation, Bacterial / physiology*
  • Multigene Family*
  • Silencer Elements, Transcriptional / genetics*


  • Bacterial Proteins
  • Biological Products