An <i>O</i> -acetylated derivative of piericidin A1 produced by <i>Kitasatospora</i> sp. A2-31 has potent activity against the cacao mirid bug, <i>Helopeltis bakeri</i> Poppius

Abstract There is an increasing demand for novel biopesticides to protect agricultural products and improve yields. To address this need, extracts from a library of Actinomycetes collected in the Philippines were evaluated against the cacao mirid bug, Helopeltis bakeri Poppius. Analysis of an active ethyl acetate extract from Kitasatospora sp. A2-31 led to the identification of a novel metabolite acetylpiericidin A1 ( 3 ) along with the known natural products piericidin A1 ( 1 ), piericidin A5 ( 2 ), chromomycin A2 ( 4 ), chromomycin A3 ( 5 ), and olivomycin A ( 6 ). Acetylpiericidin A1 demonstrated 100 % mortality against H. bakeri , while other metabolites exhibited either weak or no activity. Whole genome sequencing followed by bioinformatics analysis identified a gene downstream of the piericidin biosynthetic gene cluster that encodes a putative acetyltransferase proposed to catalyze acetylation of the C10 hydroxyl group of piericidin A1. The involvement of this gene in acetylpiericidin A1 biosynthesis was confirmed by (i) introducing an additional copy under the control of the ermE* promoter into Kitasatospora sp. A2-31, resulting in elevated production levels and (ii) through an in vitro enzymatic assay of the corresponding purified recombinant enzyme.