Nematicidal natural products discovery platform in entomopathogenic bacteria

Overview

Nematode infections create a significant global agricultural burden, yet only a few chemical nematicide classes remain available because most have been restricted due to environmental and public health concerns. This project addresses that gap by exploring entomopathogenic bacteria of the genus Xenorhabdus, which live in symbiosis with Steinernema nematodes, as a rich source of pharmaceutically interesting natural products. By engineering the biosynthetic pathways of these bacteria, the research aims to produce potent, degradable, and eco-friendly nematicidal compounds suitable for agricultural use. The work also generates broader knowledge on engineering enzymes and metabolic pathways for rapid diversification of bioactive molecules with commercial potential.

Technical specifications

• Source organism: Xenorhabdus bacteria in symbiosis with Steinernema entomopathogenic nematodes, known producers of bioactive natural products.
• Biosynthetic engineering: Targeted engineering of non-ribosomal peptide synthetase (NRPS) and NRPS-PKS hybrid biosynthetic gene clusters to unlock production of potent nematicidal metabolites that are otherwise silent under standard conditions.
• Regulatory gene identification and knockout: Identification of cluster-specific regulatory genes followed by targeted gene knockouts to confirm their role in activating nematicidal compound production.
• Enzyme engineering and promoter exchange: Engineering of biosynthetic enzymes and use of promoter exchange strategies to generate Xenorhabdus strains that overproduce target metabolites on induction.
• Bioactivity testing and structure elucidation: Strains are tested for nematicidal activity, and the specialized metabolites produced are isolated and structurally characterized to confirm identity and potency.

Technology readiness level

This is an early-stage academic research project at the discovery and pathway-engineering phase. Prior work by the team has characterized nematicidal phenotypes in Xenorhabdus and identified potent candidate natural products produced exclusively through engineering of their corresponding biosynthetic gene clusters. The proposed one-year study will validate regulatory gene function through knockouts, generate engineered strains via promoter exchange, and confirm nematicidal activity through induction-based bioassays, along with isolation and structure elucidation of the target metabolites. The platform is positioned for translational collaboration with agricultural, agrochemical, or natural product partners interested in eco-friendly nematicide development.