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1 The soybean cysteine protease inhibitor soyacystatin N (scN) and Griffonia simplicifolia lectin II (rGSII) have defense functions against the coleopteran cowpea bruchid beetle Callosobruchus maculatus. However, the ability of the insect to activate scN-insensitive digestive proteases and the relatively low potency of rGSII have hindered their practical application in plant protection. 2 Recent research suggests that defense proteins may achieve increased toxicity and durability when used in combination. Based on the structures of several natural toxin molecules, we hypothesized that covalently linked scN and rGSII could exhibit greater anti-insect efficacy than the mixture containing individual proteins. 3 To test this hypothesis, a recombinant scN-rGSII fusion protein that retained both protease inhibitor and lectin functions was constructed. 4 When fed to cowpea bruchid, this new protein showed a synergistic delay in insect development, whereas a mixture of the separate proteins only showed an additive effect. 5 Our results suggest that tethering digestive protease inhibitors to gut epithelium-interacting lectins could give plant protection superior to strategies based on single genes or mixtures of single gene products. [ABSTRACT FROM AUTHOR]