Recent advances of natural product pesticide milbemycins from Streptomyces

Abstract Milbemycins are a group of 16‐membered macrolides produced by the soil‐dwelling filamentous bacteria Streptomyces . Renowned for their potent acaricidal and insecticidal properties, combined with low toxicity, milbemycins are recognized as eco‐friendly biopesticides, vital for pest control and sustainable agricultural development. Over several decades, milbemycins have been extensively investigated, achieving significant progress, including advancements in their biological activities (such as insecticidal mechanisms and toxicity studies), biosynthetic and regulatory mechanisms, high‐yield strain engineering strategies, and the development of milbemycin‐derived commercial products for agricultural applications. This review discusses recent advances, current limitations, and ongoing and emerging efforts to overcome the limitations of milbemycin research. Finally, future research directions are outlined for the development of superior milbemycin‐producing cell factories to facilitate widespread application in the agricultural field.