The metabolic versatility of Xenorhabdus and Photorhabdus underscores their ecological significance and untapped potential as sources of novel bioactive natural products.
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.
Rare actinomycetes have emerged as important yet underexplored reservoirs for the discovery of novel bioactive compounds. Microbispora, a genus of rare actinomycetes, is widely distributed across diverse ecological niches, including terrestrial soils, marine-associated environments, plant-associated ecosystems, and insect-derived environments. To date, 81 secondary metabolites have been reported from this genus, encompassing quinones, chromones and chromanones, macrolides, other polyketides, alkaloids, peptides and diketopiperazines, and miscellaneous structural classes. These metabolites display antimicrobial, anticancer, neuroprotective, antiviral, plant growth-promoting, and enzyme inhibitory activities. Beyond systematically cataloging these compounds, this review provides an integrated analysis of their structure–activity relationships (SAR), biosynthetic origins, and biological significance. In addition, the biosynthetic potential of Microbispora is discussed based on reported genomic studies, highlighting the presence of numerous predicted and poorly characterized biosynthetic gene clusters. This review provides an integrative perspective on Microbispora as an underexplored but promising source of structurally diverse and bioactive natural products for drug discovery.
Irpex lacteus is a metabolically versatile white-rot fungus capable of producing a wide range of structurally diverse secondary metabolites, including terpenoids, phenolics, steroids, peptides, and polysaccharides. Many of these compounds exhibit notable biological activities, such as antioxidant, antimicrobial, anti-inflammatory, and cytoprotective effects, highlighting their potential relevance to food chemistry and agricultural applications. Owing to its highly efficient ligninolytic enzyme system and flexible secondary metabolic network, I. lacteus has emerged as a promising biological platform for lignocellulose valorization, microbial biotransformation, and the discovery of functional food ingredients and natural preservatives. In recent years, significant progress has been made in elucidating the chemical diversity and biosynthetic logic of its characteristic metabolites, particularly tremulane-type sesquiterpenoids with unusual skeletal rearrangements. This review systematically summarizes 226 secondary metabolites reported from I. lacteus, covering their chemical classification, biosynthetic features, biotransformation capabilities, and biological activities. Special emphasis is placed on advances enabled by genome mining, heterologous expression, and co-culture strategies that activate cryptic biosynthetic pathways. Finally, the potential applications of I. lacteus metabolites in agriculture, food chemistry, and sustainable bioprocessing are discussed, and future perspectives based on multi-omics integration and metabolic engineering are proposed.
A spore-free, high-yield, scalable production platform for oosporein was established, highlighting the potential of rare, protected fungal species as sources for valuable enzymes and bioactive secondary metabolites for efficient microbial biomanufacturing systems.
Niklas Broel, F. V. Wengner, J. Stein et al.· Journal of Agricultural and...· 0 citations
The symbiotic bacterium Photorhabdus is a rich source of bioactive secondary metabolites that mediate tripartite interactions with nematodes and insect hosts. However, natural products of ribosomal origin remain largely underexplored within this ecological niche. Here, we report the identification of aphotorhaptin A, a darobactin-like peptide (daropeptide) natural product from Photorhabdus asymbiotica, which structurally features an ether crosslink and an N-terminal acetyl unit. Biosynthetic investigation uncovers aphotorhaptin A is matured via an unexpected leader cleavage step, and the subsequent N-terminal acetylation confers metabolic stability that maintains the hexapeptide scaffold integrity. Biochemical and structural studies demonstrate the acetyltransferase PasC exhibits remarkable substrate promiscuity, facilitated by an expansive active-site cavity that accommodates diverse acyl-CoA donors and peptide substrates. Unlike the antimicrobial darobactin, aphotorhaptin A appears to lack antibacterial activity but modulates nematode development, and this activity requires the ether crosslink and the N-terminal acetyl group in the hexapeptide scaffold. These findings expand the chemical and biosynthetic space of ribosomal peptide family and establish its link with nematode development and reproduction.
Suze Ma, Ru Li, Xiangyang Gao et al.· Proceedings of the National...· 0 citations
This study demonstrates that Bacillus velezensis SPE2, a low-abundance isolate from the phycosphere of dinoflagellate, exhibits a wide degree of antagonistic activity against multiple marine Flavobacteriaceae strains, a dominant taxonomic group across the phycosphere of diverse phytoplankton species.
Runlin Cai, Hao Feng, Yang Liu et al.· Environmental Microbiome· 0 citations