Secondary metabolites of Xenorhabdus and Photorhabdus: Diversity, biosynthesis and biotechnological potential

Abstract

Xenorhabdus and Photorhabdus are Gram-negative entomopathogenic bacteria (EPB) that form mutualistic associations with nematodes and play a central role in insect pathogenesis. These bacteria are prolific producers of secondary metabolites, which exhibit remarkable structural diversity and a wide range of biological functions. The various secondary metabolites produced by these genera include peptides, lipopeptides, polyketides, hybrid non-ribosomal peptide synthase-polyketide synthase (NRPS-PKS) compounds, phenolic compounds, indole derivatives, stilbenes and other unique scaffolds. These compounds demonstrate potent antimicrobial, antifungal, cytotoxic, immunosuppressive, antiparasitic and insecticidal properties, which are crucial not only for suppressing insect host immunity and facilitating nematode reproduction but also for outcompeting other microorganisms within the insect cadaver. The biosynthesis of these metabolites is governed by complex gene clusters, often involving modular non-ribosomal peptide synthetases and polyketide synthases that are tightly regulated by global and pathway-specific mechanisms. Despite significant progress, many biosynthetic pathways remain uncharacterised, underscoring the need for more comprehensive genomic, transcriptomic and metabolomic investigations. Future research involving genome mining, synthetic biology and heterologous expression hold promise for the discovery of novel bioactive compounds. Given their potent biological activities, these metabolites have strong potential in applied sciences, including their use as environmentally friendly insecticides in agricultural biocontrol and as new antibiotics or immunomodulatory agents in pharmaceutical development. Overall, the metabolic versatility of Xenorhabdus and Photorhabdus underscores their ecological significance and untapped potential as sources of novel bioactive natural products.