Isolation and Characterization of New Sixteen-membered Macrolides from the aveA3 Gene Replacement Mutant Strain Streptomyces avermitilis TM24 with Acaricidal and Nematicidal Activities

Polyketides represent an important class of biologically active and structurally diverse compounds found in nature. They are biosynthesized from acyl CoA precursors by polyketide synthases (PKSs). The use of combinatorial biosynthesis to form hybrid PKSs is considered as an excellent approach for the development of novel polyketides. Here, ten new sixteen-membered macrolide compounds were isolated from the broth of the genetically engineered strain Streptomyces avermitilis TM24, in which the PKS gene aveA3 was seamlessly replaced by the milbemycin PKS gene milA3. Their structures were elucidated on the basis of NMR and MS spectroscopic analyses. The acaricidal and nematicidal activities of them against Tetranychus cinnabarinus and Bursaphelenchus xylophilus were evaluated. The results indicated that compound 1 exhibited potent acaricidal activity against adult mites with an LC50 value of 0.0022 mg L-1, while compounds 5 and 7 possessed potent nematicidal activity with LC50 values of 4.56 and 4.30 mg L-1, ...