Structural insights into simocyclinone as an antibiotic, effector ligand and substrate

FEMS Microbiol Rev. 2018 Jan 1;42(1):fux055. doi: 10.1093/femsre/fux055.

Abstract

Simocyclinones are antibiotics produced by Streptomyces and Kitasatospora species that inhibit the validated drug target DNA gyrase in a unique way, and they are thus of therapeutic interest. Structural approaches have revealed their mode of action, the inducible-efflux mechanism in the producing organism, and given insight into one step in their biosynthesis. The crystal structures of simocyclinones bound to their target (gyrase), the transcriptional repressor SimR and the biosynthetic enzyme SimC7 reveal fascinating insight into how molecular recognition is achieved with these three unrelated proteins.

Keywords: DNA gyrase; DNA topoisomerases; Streptomyces; aminocoumarins; antibiotics; transcription factor.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • DNA Gyrase / metabolism
  • Enzyme Activation / drug effects
  • Glycosides / chemistry*
  • Glycosides / pharmacology
  • Ligands

Substances

  • Anti-Bacterial Agents
  • Glycosides
  • Ligands
  • DNA Gyrase