Identification of the actinorhodin monomer and its related compound from a deletion mutant of the actVA-ORF4 gene of Streptomyces coelicolor A3(2)

Bioorg Med Chem Lett. 2012 Aug 1;22(15):5041-5. doi: 10.1016/j.bmcl.2012.06.005. Epub 2012 Jun 17.

Abstract

An oxygenated derivative of dihydrokalafungin (DHK) was isolated from a deletion mutant of the actVA-ORF4 gene involved in the biosynthesis of a dimeric benzoisochromanequinone (BIQ) antibiotic, actinorhodin (ACT), in Streptomyces coelicolor A3(2). Spectroscopic analysis elucidated its structure as 8-hydroxy-DHK, corresponding to the monomeric unit of ACT. Further metabolite analysis identified its related compound, clearly derived from the reduction of 8-hydroxy-DHK. The structures of these metabolites indicate the essential role of ActVA-ORF4 in ACT biosynthesis, specifically in dimerization of a BIQ intermediate via C-C bond formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones / analysis
  • Anthraquinones / metabolism
  • Anti-Bacterial Agents / analysis
  • Anti-Bacterial Agents / biosynthesis*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Chromatography, High Pressure Liquid
  • Gene Deletion
  • Magnetic Resonance Spectroscopy
  • Mutation
  • Spectrometry, Mass, Electrospray Ionization
  • Streptomyces coelicolor / metabolism*

Substances

  • Anthraquinones
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • actinorhodin