<jats:title>Summary</jats:title><jats:p>Ferrioxamines‐mediated iron acquisition by <jats:italic>Streptomyces coelicolor</jats:italic> A3(2) has recently received increased attention. In addition to the biological role of desferrioxamines (dFOs) as hydroxamate siderophores, and the pharmaceutical application of dFO‐B as an iron‐chelator, the ferrioxamines have been shown to mediate microbial interactions. In <jats:italic>S. coelicolor</jats:italic> the siderophore‐binding receptors DesE (Sco2780) and CdtB (Sco7399) have been postulated to specifically recognize and uptake FO‐E (cyclic) and FO‐B (linear) respectively. Here, disruption of the <jats:italic>desE</jats:italic> gene in <jats:italic>S. coelicolor</jats:italic>, and subsequent phenotypic analysis, is used to demonstrate a link between iron metabolism and physiological and morphological development. <jats:italic>Streptomyces coelicolor desE</jats:italic> mutants, isolated in both wild‐type (M145) and a coelichelin biosynthesis and transport minus background (mutant W3), a second hydroxamate siderophore system only found in <jats:italic>S. coelicolor</jats:italic> and related species, resulted in impaired growth and lack of sporulation. This phenotype could only be partially rescued by expression <jats:italic>in trans</jats:italic> of either <jats:italic>desE</jats:italic> and <jats:italic>cdtB</jats:italic> genes, which contrasted with the ability of FO‐E, and to a lesser extent of FO‐B, to fully restore growth at µM concentrations, with a concomitant induction of a marked phenotypic response involving precocious synthesis of actinorhodin and sporulation. Moreover, growth restoration of the <jats:italic>desE</jats:italic> mutant by complementation with <jats:italic>desE</jats:italic> and <jats:italic>cdtB</jats:italic> showed that DesE, which is universally conserved in <jats:italic>Streptomyces</jats:italic>, and CdtB, only present in certain streptomycetes, have partial equivalent functional roles under laboratory conditions, implying overlapping ferrioxamine specificities. The biotechnological and ecological implications of these observations are discussed.