Kineochelins - A new group of siderophores from an antarctic bacterium

The global rise of antimicrobial resistance has intensified the search for new microbial metabolites from underexplored environments and taxonomic groups. Extreme and geographically isolated habitats such as Antarctic terrestrial ecosystems represent promising reservoirs of biosynthetic diversity, particularly among rare and difficult-to-cultivate actinomycetes that may produce chemically diverse metabolites with potential biotechnological applications. Here, we report the characterization of kineochelins, a previously undescribed group of siderophores produced by the Antarctic isolate Actinokineospora sp. UV203, representing a difficult-to-cultivate actinomycete lineage. Structural elucidation revealed a set of closely related congeners with a mixed-ligand architecture consistent with metal-chelating activity. Genome mining combined with transcriptomic analysis identified a dedicated nonribosomal peptide synthetase-encoding biosynthetic gene cluster responsible for kineochelin production. Comparative genomic analyses indicated that, although kineochelin biosynthetic genes share limited similarity with known mixed-ligand siderophores, their gene content and organization differ substantially, suggesting a distinct biosynthetic lineage. Functional characterization of the culture supernatant and an enriched pre-purified kineochelin fraction demonstrated strong and selective iron chelation, with high affinity for ferric and ferrous iron. Crude culture extracts inhibited the growth of bacterial strains isolated from the same Antarctic environment, indicating that kineochelins may contribute to iron-mediated microbial competition. In addition, kineochelin-enriched pre-purified fractions showed moderate selective inhibitory activity against the opportunistic yeast pathogen Nakaseomyces glabratus and a clinical isolate of Saccharomyces cerevisiae associated with invasive infection. These findings expand the chemical and biosynthetic diversity known within the genus Actinokineospora and demonstrate that Antarctic rare actinomycetes represent valuable sources of previously unexplored natural products. The discovery of kineochelins highlights the potential of genome-guided exploration of polar microorganisms for identifying bioactive metabolites with relevance for antimicrobial discovery and biotechnology.