Heterocyclic stable peptides as novel selective peptide insecticides for sustainable crop protection

Overview

Ventera Bio is pioneering a new class of selective peptide insecticides (PIPs) derived from naturally evolved venom peptides. The approach targets plant-feeding pests in the orders Lepidoptera and Hemiptera, which last shared a common ancestor with pollinators (Hymenoptera) approximately 400 million years ago. By exploiting this deep evolutionary divergence, the platform identifies peptides that are biologically active against pests while remaining harmless to beneficial pollinators such as bees. The result is a targeted, biodegradable, and environmentally responsible crop protection solution designed to replace harmful synthetic chemical pesticides and reduce the development of insect resistance.

Technical specifications

Discovery platform:

• Bioinformatic alignment of target protein sequences from pest and pollinator species using BLAST to identify regions of biological impact and evolutionary divergence
• Design and construction of a Targeted Venom Discovery Array (T-VDA) built from bespoke fractions of venom-derived peptide libraries
• High-Throughput Time-Resolved Fluorescence (HTRF) assays developed against selected pest-specific protein targets, including proteins involved in ecdysis where rapid growth stages increase vulnerability
• Concentration-response confirmation and intact mass identification of hit fractions using electrospray mass spectrometry and double-digest peptide analysis
• Peptide structure-activity relationship (SAR) studies to pinpoint active regions and propose sequences for expression and feeding trials

Key peptide characteristics:

• Heterocyclic stable folds that resist environmental degradation
• Membrane-penetrant properties enabling efficient bioactivity
• High molecular precision derived from millions of years of venom evolution
• Demonstrated antifeedant and lethal activity in aphid models (Acyrthosiphon and Myzus) within four days
• Successful expression of venom peptides in tobacco plant systems, confirming feasibility for plant-based production

Supply chain and infrastructure:

• Full control of venom supply from source animals, compliant with Nagoya Protocol requirements
• Proprietary ultra-high-performance liquid chromatography (uHPLC) fractionation capabilities
• State-of-the-art automated, high-throughput R&D screening platforms producing data-rich results for agricultural partners

Technology readiness level

The platform has been validated through prior work demonstrating that venom libraries serve as excellent sources of new ligands in HTRF-based screening, as presented at the 2021 ELRIG Drug Discovery conference. Existing data confirm antifeedant and lethal activity of venom fractions against aphid pest species. Feasibility of plant-based peptide expression has also been demonstrated in tobacco. The next phase of validation involves confirming target protein knowledge across pest and pollinator species, building and validating new HTRF assays, screening the full venom library, confirming hits in concentration-response format, and advancing active sequences into PIP expression trials and insect feeding assays.