Background; The distribution, diversity, and phylogeny of siderophores in cyanobacteria have significant environmental, medical and biotechnological applications. Siderophores are iron-chelating compounds produced by microorganisms to facilitate iron uptake1.
Objectives: This study investigated the three types of cyanobacterial siderophores: hydroxamates, catecholates, and carboxylates and identified potential novel siderophores within this diverse and widespread phylum.
Methods: Cyanobacterial genomes were downloaded from NCBI and after quality assessment, 785 genomes were included for further analysis. These genomes were annotated using Prokka (version 1.14.5) and a comprehensive alignment of genomes was generated using a set of 400 universal proteins from the PhyloPhlAn database (PhyloPhlAn version 3.0.60). In addition to established genome mining tools like antiSMASH (version 3.1), siderophore biosynthetic enzymes were identified using hidden markov models (HMMs) from InterPro, and HMMs developed in-house. Predicted gene clusters were organised into sequence similarity networks using BiG-SCAPE (1.1.2) to investigate pathway conservation.
Results: Putative siderophores were identified across seven cyanobacterial orders. Hydroxamates were present in 5.1% of the samples, predominantly in the Nostocales and Oscillatoriales orders, and mainly in host-associated environments. Catecholates were more common, found in 15% of the samples, especially in the Pleurocapsales, Nostocales, and Chroococcidiopsidales orders, and were primarily found in host-associated and terrestrial environments. Carboxylates appeared in 6.5% of the samples, with a similar distribution to catecholates.
Conclusions: The study highlights the genetic diversity of catecholate and carboxylate siderophores, which could not be grouped into lineages due to their diversity. Given their widespread presence in cyanobacteria, catecholates are hypothesized to be the primary siderophore, although they are the least biochemically characterized and absent in several cyanobacterial orders. However, this absence in particular clades reveal genomes with novel clusters worthy of further investigation. These findings enhance our understanding of iron metabolism in cyanobacteria and the ecological roles of siderophores in broader environmental contexts.