Next generation biopesticides for environmentally benign control of crop pests

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Pesticides are an essential tool for increasing agricultural productivity and meeting the challenge of providing increased food supplies from diminishing land areas available for cultivation. Invertebrate pests of crops, which include both insects and other arthropods, such as caterpillars, aphids, beetles, flies and mites, and molluscs, such as slugs and snails, can cause total crop losses if not treated. However, the negative effects of unregulated use of indiscriminate chemical pesticides on the environment, and human health, are well-documented. In the search for new environmentally-friendlypesticides, many investigators have identified the possibility of using examples from the wide range of protein and peptide toxins produced naturally by organisms such as spiders, scorpions and other predators to control insect and other invertebrate pests. These toxins have many advantages - they are effective, can be highly specific in their action, with no effects on higher animals; they are also susceptible to biodegradation in the environment. However, delivery of these toxins to their sites of action - usually in the central nervous system - has remained a consistent problem which has prevented their adoption as pesticides; whereas a predatory organism can sting or bite its prey to introduce toxins into its circulatory system, delivery through contact or feeding by the target organism is usually ineffective.Fusion protein technology enables the conversion of a protein or peptide toxin which normally requires access to the circulatory system of an organism to be effective, into a pesticide which is effective when orally delivered. This is achieved by fusion of the toxin to a protein "carrier", which is able to transport across the gut wall of the target organism into the circulatory system. The fusion protein, containing both the toxin and the carrier in a single polypeptide, is produced from a synthetic gene in a recombinant expression system, either for exogenous application or produced endogenously in the crop. When the target organism ingests material containing the fusion protein, the toxin component of the fusion is transported by the "carrier" into the circulatory system; it is now able to access its targets. Fusion proteins are thus effective pesticides in baits or sprays. Fusion protein technology has been developed to produce novel pesticides which are more specific towards target species, with minimal side effects on beneficial organisms, such as bees. Since fusion proteins are biodegradable, they do not persist in the environment, which is timely in view of current concerns about molluscicide residues in water supplies.The proposed project aims to develop two prototype fusion proteins, which have been shown to have insecticidal activity towards caterpillars, beetles, flies and aphids, and molluscicidal activity towards slugs, to the point where a prototype biopesticide is ready for evaluation in a commercial setting, in collaboration with potential customers. This will involve optimising the production process, and carrying out formulation and product development. At the same time the necessary background testing for preparing data for pesticide registration will be accumulated; this will include evaluation of both efficacy towards target pests, and ecotoxicological and environmental studies. The project will also aim to develop further fusion protein biopesticides, to allow a portfolio of products suitable for different applications to be built up. It will also look at development of resistance towards fusion protein biopesticides in potential targets, to develop a strategy for managing use of these products to minimise loss of effectiveness; the availability of a range of fusion proteins with differing modes of action will also be a valuable resource in resistance management.