Location: Horticultural Crops Research Unit
Title: GPCR-based bioactive peptide screening using phage-displayed peptides and an insect cell system for insecticide discoveryAuthor
Submitted to: Biomolecules EISSN 2218-273X
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 4/13/2021 Publication Date: 4/16/2021 Citation: Choi, M.Y., Vander Meer, R.K. 2021. GPCR-based bioactive peptide screening using phage-displayed peptides and an insect cell system for insecticide discovery. Biomolecules EISSN 2218-273X. 11(4). Article 583. https://doi.org/10.3390/biom11040583. DOI: https://doi.org/10.3390/biom11040583 Interpretive Summary: The typical high-throughput screening for insecticide discovery is a high-risk process with a low probability of success. To develop a new specific class of insecticides, insect G-protein coupled receptors (GPCRs) have been considered targets for decades, but little progress was made until now. We recently established a novel GPCR-based screening for insecticide discovery using insect cells, and successfully isolated small bioactive peptides for pest control. Application of our new technology for insecticide discovery suggests multiple advantages: 1) use of inexpensive materials; 2) simple and fast processing with an insect cell-based screening system; and 3) a variable target sites to minimize resistance problems from conventional insecticides. Therefore, the technology will be a new avenue in integrated pest management (IPM). Technical Abstract: Discovery of new insecticides improves insect pest management (IPM) but is a long iterative process with low chances of success and high risk. For over two decades, insect neuropeptides (NPs) and their G-protein coupled receptors (GPCRs) have been considered as biological targets for discovery of new specific classes of pesticides because they are involved in almost all physiological processes during insect life stages. A key roadblock to success is how to efficiently screen large chemical libraries, including natural products for active compounds. New technologies, such as ‘omics’ and many biological tools are now available and should facilitate development of a new approach. In this study, we report a novel GPCR-based screening technology using a phage peptide library and a biopanning method in an insect cell system. This report provides the first proof-of-concept for the development of novel IPM strategies using neuropeptides and GPCRs. Using the fire ant as a model system, bioactive peptides were isolated and identified. The novel small peptides interfere with the target GPCR-ligand functions. Therefore, we refer to this new mechanism as “receptor interference” (Receptor-i). The GPCR-based bioactive screening suggests multiple advantages, including a manageable size (20-30 genes) of target genes, rapid screening process, and flexible delivery methods such as topical, ingestion, and plant-incorporated protectants as a Bt toxin alternative. |