Production of 6,8a-seco-6,8a-deoxy derivatives of avermectins by a mutant strain of Streptomyces avermitilis.
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.
Pang
C H
CH
School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Matsuzaki
K
K
Ikeda
H
H
Tanaka
H
H
Omura
S
S
D000871:Anthelmintics / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D005798:Genes, Bacterial; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D016296:Mutagenesis; D009154:Mutation; D013302:Streptomyces / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D000871:Anthelmintics; D000981:Antiprotozoal Agents; D004269:DNA, Bacterial; D007559:Ivermectin; C019264:avermectin