Ferrioxamine X1 mediated iron interaction with FoxA receptor in marine Pseudomonas stutzeri: An in silico approach

Abstract

The low iron concentrations in the Equatorial Indian Ocean (EIO) create a challenging environment for microbial life, requiring microorganisms to adapt. One strategy involves the production of siderophores, organic compounds that bind to Fe³⁺ ions and facilitate their uptake through specific receptors. Multiple siderophores may improve the bioavailability of iron due to the varied structures of siderophores and receptors. Since a single receptor may bind multiple siderophores, it is imperative to understand the molecular mechanisms underlying the interaction between siderophores and their receptors. This study used an in silico approach to explore these interactions. Pseudomonas stutzeri ATCC 17588, isolated from the EIO, was optimized for siderophore production under various growth conditions and analyzed using LC-qTOF-MS. The tertiary structure of the FoxA receptor and its interaction with the ferrioxamine X₁-Fe³⁺ complex were examined through molecular docking. P. stutzeri ATCC 17588 produced multiple siderophores, including ferrioxamine X₁, with optimal production at 10 nM iron concentration, pH 8.5, and 25 °C. The interaction energies between ferrioxamine X₁-Fe³⁺ and the FoxA receptor were − 40.81 kcal/mol and − 9.3 kJ/mol, respectively, suggesting stable complexes. The predicted FoxA structure, validated through various analyses, revealed helices interspersed with strands. Hydrophobic interactions, involving residues such as Gln287, Arg792, and Glu180, were primarily responsible for the binding of ferrioxamine X₁-Fe³⁺ to the FoxA receptor. This study sheds light on the role of ferrioxamine X₁ in iron acquisition by P. stutzeri in the iron-limited EIO and enhances our understanding of microbial metal-ligand interactions in marine ecosystems.