Characterization of trehalase from Acyrthosiphon pisum for the design of new insecticides

Summary

Aphids are major pests in agriculture, causing direct damage to plants and acting as vectors for phytopathogenic viruses. Conventional insecticides are widely used to control them, but their toxicity and efficacy pose problems in terms of the environment, human health and the emergence of resistance to these compounds. New alternatives are therefore needed, such as biological control using predators or parasitoids. However, these methods are not always economically viable on a large scale. As part of this thesis, another approach is being explored which involves developing new insecticides targeting the biochemical functions of aphids.

The project aims to discover new inhibitors of trehalase, an enzyme essential for insect energy metabolism. Inhibition of this enzyme could disrupt vital insect functions without affecting mammals. This research involved several stages: the purification and complete characterization of trehalase from Acyrthosiphon pisum (the model for this study), the in vivo, in vitro and in silico analysis of commercial inhibitors on this enzyme, before moving on to the search for new inhibitors. Two points of integrated insect management were explored, biological and chemical control.

The biological side saw the study of a strain of Streptomyces naturally producing trehalase-inhibiting metabolites, notably validamycin A, a molecule recognized in the literature as one of the best inhibitors, but not applicable as an insecticide. Other molecules appear to have interesting features, but we have not been able to isolate and characterize them.
The chemical side has enabled us to create a pharmacophore hypothesis based on experimental results on molecules obtained by virtual screening. Although these molecules are not usable as insecticides as they stand, this hypothesis provides a better understanding of trehalase inhibitors in general and can be used to refine future analyses.

Jury

  • Prof. Jean-Yves MATROULE (UNamur), president
  • Dr Catherine MICHAUX (UNamur), promoter and secretary
  • Prof. Frédéric FRANCIS (ULiège), co-promoter
  • Prof. André MATAGNE (ULiège)
  • Dr Rudy CAPARROS (ULiège)
  • Dr Morgan HANS (Biocidal)