Siderophore-mediated iron uptake in cyanobacteria: current insights and knowledge gaps compared with model heterotrophic bacteria

Iron is indispensable for most organisms, but it is often not easily available in the natural environments. This constraint has considerable impact on cyanobacteria, which require large amounts of iron to support several physiological processes, prominent among them being photosynthesis and, in some species, nitrogen fixation. To overcome iron limitation, many cyanobacteria produce low-molecular-weight, strong iron-sequestering molecules called siderophores, and employ specialized transport systems for environmental iron acquisition. Although these systems share similarities with those of well-characterized heterotrophic bacteria, our understanding of siderophore-mediated iron uptake in cyanobacteria remains limited. To date, only a handful of cyanobacterial siderophores have been structurally identified, and few genes involved in their biosynthesis, transport, and regulation have been reported, but a complete understanding of these processes remains lacking. This review first briefly discusses the well-established siderophore biosynthesis, transport, and regulatory systems of the model heterotrophic bacteria Escherichia coli and Pseudomonas aeruginosa, as a comparative framework. It further discusses the current understanding of siderophore systems in cyanobacteria, highlighting similarities and differences with heterotrophic bacteria, species-specific variations among cyanobacteria, and major knowledge gaps. The review also discusses the ecological significance of cyanobacterial siderophores and their emerging applications in heavy metal bioremediation. Overall, this review identifies important directions for future research, including expanded structural characterization of cyanobacterial siderophores, deeper investigation of their biosynthesis, transport, and regulatory pathways, and improved understanding of their ecological functions and environmental applications. Addressing these gaps will strengthen our mechanistic understanding of siderophore-mediated iron uptake in cyanobacteria and its environmental relevance.