title: Construction of a doramectin producer mutant from an avermectin-overproducing industrial strain of Streptomyces avermitilis.
abstract: The avermectin analogue doramectin (CHC-B1), which is produced in mutants that have an altered biosynthesis pathway of avermectin, is one of the most effective agricultural pesticides and antiparasitics. We report here the construction of a bkdF olmA double-deletion mutant lacking one of the branched-chain alpha-keto acid dehydrogenase encoding genes (bkdF) and the oligomycin PKS encoding gene cluster (olmA) in Streptomyces avermitilis 76-05. We then characterized the production of various antibiotics in cultures of the deletion mutant. In a fermentation medium supplemented with cyclohexanecarboxylic acid, this double mutant produced doramectin and its analogues but no oligomycin. The mutant proved to be genetically stable, without any antibiotic resistance markers inserted into its chromosome, and could potentially become an industrial doramectin-producing strain after further improvement.
authors.affiliation: Department of Microbiology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Xuejin
authors.initials: X
authors.lastname: Zhao
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Wang
authors.forename: Shiwei
authors.initials: S
authors.lastname: Wang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Wen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
mesh_terms: D000871:Anthelmintics / Q000378:metabolism*; D005285:Fermentation; D017353:Gene Deletion; D005818:Genetic Engineering; D007218:Industrial Microbiology; D007306:Insecticides / Q000378:metabolism*; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000235:genetics; D005810:Multigene Family; D009154:Mutation; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D048630:Polyketide Synthases / Q000235:genetics; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D000871:Anthelmintics; D007306:Insecticides; D009097:Multienzyme Complexes; D007559:Ivermectin; C019264:avermectin; D048630:Polyketide Synthases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C038808:2-methylacyl-CoA dehydrogenase; C084101:doramectin