Iron Binding before Iron Limitation: Siderophore synthesis arose well before iron became a limiting element

Abstract It is widely accepted that the use of siderophores, small molecules that bind and solubilize iron, emerged as a response to the dramatic reduction in bioavailability of this metal in aquatic environments caused by precipitation of iron oxides associated with the Great Oxidation Event (GOE). Here, we report a molecular clock analysis of the time of emergence of siderophore biosynthesis and utilization genes that challenges this view and argues for an emergence of these secondary metabolites that largely predates GOE. The emergence date of NIS siderophore synthases is found to predate by more than 1 Gy the emergence date of ferric siderophore reductases and esterases, which in turn also predate the GOE by approximately1Gy. This temporal gap is surprising given that these enzymes are essential for microorganisms to obtain iron from siderophores. This timing of events raises questions on the original ecological drivers for the emergence of siderophores. We offer an alternative hypothesis for the origin of siderophores which is their use in ferric mineral dissolution to avoid incrustation of neutrophilic iron oxidizers by metabolically generated ferric iron minerals. The observations and hypothesis reported here highlight the importance of environmental microbe-mineral interactions, beyond nutrient acquisition, as critical selective forces in early Earth, and call for a reassessment of the timing and drivers of siderophore evolution.