Microbial Secondary Metabolite, Phlegmacin B1, as a Novel Inhibitor of Insect Chitinolytic Enzymes.

Abstract

Periodic chitin remodeling during insect growth and development requires a synergistic action of two glycosyl hydrolase (GH) family enzymes, GH18 chitinase and GH20 β-N-acetylhexosaminidase (Hex). Inhibiting either or both of these enzymes is a promising strategy for pest control and management. In this study, OfChi-h (a GH18 chitinase) and OfHex1 (a GH20 Hex) from Ostrinia furnacalis were used to screen a library of microbial secondary metabolites. Phlegmacin B1 was found to be the inhibitor of both OfChi-h and OfHex1 with Ki values of 5.5 μM and 26 μM, respectively. Injection and feeding experiments demonstrated that phlegmacin B1 has insecticidal effect on O. furnacalis's larvae. Phlegmacin B1 was predicted to bind to the active pockets of both OfChi-h and OfHex1. Phlegmacin B1 also showed moderate inhibitory activities against other bacterial and insect GH18 enzymes. This work provides an example of exploiting microbial secondary metabolites as potential pest control and management agents.