Gene Replacement for the Generation of Designed Novel Avermectin Derivatives with Enhanced Acaricidal and Nematicidal Activities

• DOI: 10.1128/aem.01025-15
• Publication Date: 2015-05-30T05:42:50Z
• Authors: Jun Huang; An-Liang Chen; Hui Zhang; Zhen Yu; Mei-Hong Li; Na Li; Jia-Tan Lin; Hua Bai; Ji-Dong Wang; Yu-Guo Zheng
• Keywords: Avermectin

ABSTRACT Avermectin (AVM) and ivermectin (IVM) are potent pesticides acaricides which have been widely used during the past 30 years. As insect resistance to AVM IVM is greatly increasing, alternatives urgently needed. Here, we report two novel derivatives, tenvermectin A (TVM A) TVM B, considered a potential new generation of agricultural veterinary drugs. The molecules TVMs were designed based on structure pharmacological property comparisons among AVM, IVM, milbemycin (MBM). To produce TVMs, genetically engineered strain, MHJ1011, was constructed from Streptomyces avermitilis G8-17, an industrial strain. In native aveA1 gene seamlessly replaced with milA1 hygroscopicus . total titer produced by MHJ1011 reached 3,400 mg/liter. Insecticidal tests proved that had enhanced activities against Tetranychus cinnabarinus Bursaphelenchus xylophilus , as desired. This study provides typical example exploration for active compounds through method polyketide synthase (PKS) reassembly replacement. results insecticidal may be use in elucidating structure-activity relationship AVMs MBMs.