Initiation of actinorhodin export in Streptomyces coelicolor

Mol Microbiol. 2007 Feb;63(4):951-61. doi: 10.1111/j.1365-2958.2006.05559.x.


Many microorganisms produce molecules having antibiotic activity and expel them into the environment, presumably enhancing their ability to compete with their neighbours. Given that these molecules are often toxic to the producer, mechanisms must exist to ensure that the assembly of the export apparatus accompanies or precedes biosynthesis. Streptomyces coelicolor produces the polyketide antibiotic actinorhodin in a multistep pathway involving enzymes encoded by genes that are clustered together. Embedded within the cluster are genes for actinorhodin export, two of which, actR and actA resemble the classic tetR and tetA repressor/efflux pump-encoding gene pairs that confer resistance to tetracycline. Like TetR, which represses tetA, ActR is a repressor of actA. We have identified several molecules that can relieve repression by ActR. Importantly (S)-DNPA (an intermediate in the actinorhodin biosynthetic pathway) and kalafungin (a molecule related to the intermediate dihydrokalafungin), are especially potent ActR ligands. This suggests that along with the mature antibiotic(s), intermediates in the biosynthetic pathway might activate expression of the export genes thereby coupling export to biosynthesis. We suggest that this could be a common feature in the production of many bioactive natural products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / metabolism
  • Anti-Bacterial Agents / metabolism
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biological Transport
  • Biosensing Techniques
  • DNA, Bacterial / metabolism
  • Gene Expression Regulation, Bacterial / drug effects
  • Ligands
  • Multigene Family
  • Mutation
  • Naphthalenes / metabolism
  • Naphthoquinones / metabolism
  • Pyrans / metabolism
  • Repressor Proteins / drug effects
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Streptomyces coelicolor / drug effects
  • Streptomyces coelicolor / genetics
  • Streptomyces coelicolor / metabolism*
  • Tetracycline / pharmacology


  • 4-dihydro-9-hydroxy-1-methyl-10-oxo-3-H-naphtho-(2,3-c)-pyran-3-acetic acid
  • Anthraquinones
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • DNA, Bacterial
  • Ligands
  • Naphthalenes
  • Naphthoquinones
  • Pyrans
  • Repressor Proteins
  • tetracycline resistance-encoding transposon repressor protein
  • kalafungin
  • Tetracycline
  • actinorhodin