Acyltransferase Domain Swapping for the Production of Tenvermectin B Metabolites in Genetically Engineered Strain Streptomyces avermitilis HU02

Abstract

Tenvermectins A and B (TVMs A and B) are hybrid natural compounds of avermectins and milbemycins with enhanced insecticidal activity. Aiming at obtaining a strain for the production of the higher activity metabolite–TVM-B as a major constituent, a recombinant strain Streptomyces avermitilis HU02 was constructed by a domain swapping strategy in which milA1-AT0 gene in S. avermitilis MHJ1011 was replaced by eryA1-AT0 gene from Saccharopolyspora erythraea ATCC 40137. Chemical investigation on the culture of S. avermitilis HU02 led to the isolation of a large amount of TVM-B and trace amounts of five new TVM-B analogues. The structures of new metabolites were elucidated by extensive spectroscopic analysis including 1D and 2D nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The bioassay test indicated that five new TVM-B analogues exhibited potent insecticidal activity against Tetranychus cinnabarinus and Bursaphelenchus xylophilus. This study provided a feasible route to the low-cost production of TVM-B and enriched the structural diversity of TVM-B metabolites.