title: Production of doramectin by rational engineering of the avermectin biosynthetic pathway.
abstract: In an attempt to construct a strain that produces doramectin, the loading module of Ave polyketide synthase (PKS) from Streptomyces avermitilis M1 was replaced with a cyclohexanecarboxylic (CHC) unique loading module from phoslactomycin PKS. Additionally, the CHC-CoA biosynthetic gene cassette was introduced into the engineered strain, which provided the precursor for directed biosynthesis of doramectin. The doramectin production ability of the final mutant S. avermitilis TG2002 was increased about six times and the ratio of Dor to Ave was enhanced 300 times more than the original strain.
authors.affiliation: State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Rd., Shanghai 200032, China.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Hai-Xue
authors.initials: HX
authors.lastname: Pan
authors.forename: Gong-Li
authors.initials: GL
authors.lastname: Tang
mesh_terms: D000871:Anthelmintics / Q000737:chemistry / Q000378:metabolism; D053898:Biosynthetic Pathways / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D015964:Gene Expression Regulation, Bacterial; D005818:Genetic Engineering; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism
chemical_list: D000871:Anthelmintics; D011994:Recombinant Proteins; D007559:Ivermectin; C019264:avermectin; C084101:doramectin