Protein prenylation in insects: a potential target for the development of bio-rational insecticides targeting the Lepidoptera?

摘要

Short-chain prenyltransferases (farnesyl diphosphate synthase [FPPS] and geranylgeranyl diphosphate synthase [GGPPS]) and protein-prenyltransferases (farnesyltransferase and geranylgeranyltransferase) are enzyme families involved in the synthesis of C-15 and C-20 prenyl moieties and in their attachment to the carboxyl-termini of a variety of eukaryotic proteins, respectively. Given that protein prenylation is an important post-translational modification essential for the localization and activation of many proteins, these enzymes have been the focus of many studies in mammals, with a view to developing new therapeutic tools for the treatment of cancer. In insects, only FPPS and GGPPS have been characterized to date. FPPS displays unique features in the Lepidoptera, thereby making it a potential target for the development of bio-rational insecticides that can disrupt key pathways, such as juvenile hormone biosynthesis and protein prenylation. Further characterization of insect FPPS and GGPPS, and biochemical investigations of insect protein-prenyltransferases may provide the foundation for the development of bio-rational insecticides targeting protein prenylation.