Group h Chitinase: A Molecular Target for the Development of Lepidopteran-Specific Insecticides

Sustainable agriculture requires insecticides that are selective between insects and mammals and even between harmful and beneficial insects. Lepidoptera includes the largest number of insect pests that threaten crops, and Hymenoptera contains the natural enemies for these pests. Discovery of lepidopteran-specific molecular targets is one route to develop such selective pesticides. Group h chitinase (Chi-h) is an ideal target for lepidopteran-specific insecticides because it is only distributed in Lepidoptera and is critical to their molting processes. This minireview focuses on the latest progress in developing Chi-h as a lepidopteran-specific insecticide target. We describe the biological function, crystal structure, and small-molecule inhibitors of the enzyme. Notably, two unique pockets were discovered in the crystal structure of Chi-h for the binding of the selective inhibitors, phlegmacin B₁ and lynamicin B. Moreover, lynamicin B was found to exhibit significant insecticidal activity toward lepidopteran pests but is harmless toward their natural enemies. These findings are advancing the development of selective insecticides to meet the needs of sustainable agriculture.