Genome Mining Approaches for Toxicant Discovery: A Case Study Examining Receptor Proteins for Pest Management in New Zealand

Pest control is a global challenge for agriculture and biodiversity conservation, with the use of existing vertebrate pesticides increasingly constrained by regulatory, environmental, and social pressures. There is an urgent need for safer and more species‐selective toxicants, but the development of novel vertebrate pesticides remains technically challenging. Novel methods to identify putative pathways for development are needed. Therefore, we focused on G protein‐coupled receptors (GPCRs) for exploring a proof‐of‐concept approach for the identification of potential toxicant protein targets in an Aotearoa New Zealand (NZ) conservation context, where invasive mammalian predators are the focus of pest control. GPCRs are a pharmacologically rich protein family extensively studied in humans and other model organisms. We evaluated two approaches for retrieving GPCR sequences from existing genomic databases, which both delivered comprehensive receptor repertoires for NZ pest and non‐target species. We explored protein sequence, structure and toxicological relevance for a subset of GPCRs. We identified receptors exhibiting interspecific sequence and structural variation that may warrant further investigation for species‐selective toxicant development. We also discuss the current challenges in progressing from candidate protein targets to validated toxicants. Although these represent early‐stage findings within the broader pipeline of vertebrate toxicant development, our results show how genome mining approaches can support early prioritisation of toxicant protein targets by comparing proteins between pest and non‐target species.