Comparative genomics and advanced mining of Photorhabdus isolates reveals cryptic polyketide synthase clusters and potent anti-staphylococcal activity

2026 · doi:10.1099/acmi.0.001220.v1
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Full text loading... Abstract This study explores the genomic and functional potential of five newly sequenced Photorhabdus isolates. Phylogenomic reconstruction and average nucleotide identity analysis definitively reclassified the isolates as Photorhabdus hainanensis (strain KLK8.1) and Photorhabdus akhurstii (strains KLK18.5, NMP12.2, NMP13.3, and NMP13.5). Comprehensive genome mining identified a total of 134 biosynthetic gene clusters (BGCs), comprising a core secondary metabolome essential for symbiosis and a substantial proportion (~60%) of uncharacterized clusters. Significantly, deep-learning-assisted annotation highlighted rare highly reducing type II polyketide synthase (HR-T2PKS) clusters, which are predicted to produce novel polyenes. Bioactivity profiling corroborated this high biosynthetic potential; whole-cell suspensions exhibited limited inhibition, while crude extracts displayed potent, concentration-dependent efficacy against Staphylococcus aureus. These results establish these Photorhabdus strains particularly P. hainanensis strain KLK8.1 as high-value reservoirs for the discovery of novel polyene and peptide-derived antimicrobials. - Received: - Version Posted: Funding - Naresuan University (NU), and National Science, Research and Innovation Fund (NSRF) (Award R2567B031) - Principal Award Recipient: Aunchalee Thanwisai

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