Production of 6,8a-seco-6,8a-deoxy Derivatives of Avermectins by a Mutant Strain of Streptomyces Avermitilis

J Antibiot (Tokyo). 1995 Jan;48(1):59-66. doi: 10.7164/antibiotics.48.59.

Abstract

Streptomyces avermitilis produces the anthelmintic and insecticidal secondary metabolite avermectins. Following mutagenesis of a recombinant strain, S. avermitilis K2038 (aveD X) with N-methyl-N'-nitro-N-nitrosoguanidine, a derivative strain K2057 (aveD aveE X), was isolated, which produced seven avermectin-related compounds different from the eight components of avermectins. Four among these seven compounds from mutant K2057 were found to be new metabolites. Their structures were 4'-deoleandrosyl-6,8a-seco-6,8a-deoxyavermectin B1a, 4'-deoleandrosyl-6,8a-seco-6,8a-deoxy-5-oxoavermectin B1a, 4'-deoleandrosyl-6,8a-seco-6,8a-deoxy-5-oxoavermectin B2a and 6,8a-seco-6,8a-deoxy-2,5-didehydroavermectin B2a, all of which lack the furan ring at C-6, C-8a. The mutation affecting the formation of the furan ring (aveE) is located in the center of the gene cluster for avermectin biosynthesis.

MeSH terms

  • Anthelmintics / chemistry
  • Anthelmintics / isolation & purification
  • Anthelmintics / metabolism*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / isolation & purification
  • Antiprotozoal Agents / metabolism*
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Cloning, Molecular
  • DNA, Bacterial / genetics
  • Genes, Bacterial
  • Ivermectin / analogs & derivatives*
  • Ivermectin / chemistry
  • Ivermectin / isolation & purification
  • Ivermectin / metabolism
  • Mutagenesis
  • Mutation*
  • Streptomyces / chemistry
  • Streptomyces / genetics*
  • Streptomyces / metabolism*

Substances

  • Anthelmintics
  • Antiprotozoal Agents
  • DNA, Bacterial
  • Ivermectin
  • avermectin