Design of novel recombinant fusion proteins for use as bioinsecticides

Abstract

Insecticidal compounds play a pivotal role in effective crop protection strategies. The remarkable adaptability and resilience of herbivorous insect pests has led to widespread insecticidal resistance, rendering many traditional compounds ineffective. Combatting this issue requires effective modern pest control and insecticidal resistance management strategies, which can be realised through the diversification of our insecticidal repertoire. Nature itself offers a vast array of biochemistries suitable for this purpose, with millions of insectivorous species that produce potent, taxonomically selective, and biodegradable toxins.
This thesis presents a multifaceted approach to the initial evaluation, development, and design of innovative, recombinant snowdrop lectin (Galanthus nivalis agglutinin)-based fusion protein bioinsecticides. While investigating various design paradigms, the discussion centres around the inhibitor cysteine knot (ICK), a structural motif or protein scaffold adopted by neurotoxic peptides from a wide range of venomous and poisonous creatures. The repeated convergence upon this structure, particularly among insectivorous arachnids, demonstrates its flexibility and utility. This thesis thus demonstrates a multitude of promising biochemistries and insecticidal modes of action for consideration as lead compounds for bioinsecticide development, as well as the implementation of computationally assisted design systems, and novel bioengineering approaches. By these means, this research seeks to expand the arsenal of bioactive compounds available to combat insecticide resistance and avoid non-target effects on beneficial species.
The novel insecticidal compounds, recombinant fusion technologies, and AI supplemented design techniques discussed in this thesis, each contribute towards the endeavour to enhance the number of insecticidal control measures. By assessing novel compounds, with potentially unique modes of action and specific target sites, and establishing rapid and accessible design techniques to enhance and modulate the insecticidal activity of natural neurotoxic compounds, the diversity of the repertoire of effective and ecologically safe bioinsecticides for use in the protection of crops is possibly limitless.