SCIENTISTS ENGINEER NATURAL INSECTICIDE TO BE MORE DEADLY
COLUMBUS, Ohio -- Scientists at Ohio State University have engineered changes in a common biological insecticide that make it four times as toxic to young gypsy moth larvae as the most potent gypsy moth toxin currently available.
The insecticide -- a toxin produced by the common soil bacterium Bacillus thuringiensis -- kills gypsy moth larvae and other insects by binding to receptor molecules in their midgut region. The re-engineered toxin binds more readily to these receptor molecules, and thus is more toxic to insects.
What we intended to do was to show that its possible to increase toxicity by increasing receptor binding, and we did that. The improved toxicity was directly attributable to enhanced binding affinity to the receptor molecules, said Donald H. Dean, a professor of biochemistry, entomology and molecular genetics at Ohio State and a co-author of the study.
These results strongly suggest the possibility of engineering novel toxins that are more toxic to a wider variety
of insects, which would meet the needs of the agricultural industry, he said. We think this is just the beginning of a series of mutations that could be made in B. thuringiensis toxin to target more important agricultural pests.
Dean conducted this research with Francis Rajamohan, research associate; Oscar Alzate, graduate student; Jeffrey A. Cotrill, research aide; and April Curtiss, research associate, all from Ohio State. The groups work was published in a recent issue of the Proceedings of the National Academy of Sciences.
For their study, the scientists substituted various amino acids naturally found in the B. thuringiensis toxin molecule with other amino acids. These switches produced mutant strains of the B. thuringiensis toxin. The scientists applied four different mutant B. thuringiensis toxins to areas of the moth midgut region to see how readily the toxins bound to the midgut receptor molecules.
The results showed that one of the mutant toxins -- dubbed DF-1 -- was four times as lethal as the most potent known gypsy moth toxin, Dean said. The other mutant toxins, while more toxic than unaltered B. thuringiensis toxin, were not as toxic as DF-1.
The reasons for the mutant agents greater toxicity likely lie in the size and other qualities of the substituted amino acid residues, Dean said. Our results suggest that a smaller side chain provides the toxin a closer contact with the binding pocket, which in turn increases the affinity, he said.
Dean said he and his colleagues hope to repeat the success of this study and engineer a B. thuringiensis toxin thats more effective against important agricultural pests, such as corn earworm, European corn borer, beet army worm and cabbage looper. Because it is not harmful to humans, such a toxin would have clear advantages over chemical insecticides, Dean said.
A four- to 10-fold improvement in toxicity there would be viewed as very significant and a very important contribution to safely controlling agricultural pests, he said. Thats going to be our future direction.
Contact: Donald H. Dean, (614) 292-8829; Dean.10@osu.edu
Written by Kelly McConaghy Kershner, (614) 292-8308; Kershner.4@osu.edu