Multiple biosynthetic and uptake systems mediate siderophore-dependent iron acquisition in Streptomyces coelicolor A3(2) and Streptomyces ambofaciens ATCC 23877

Abstract

Siderophore-mediated iron acquisition has been well studied in many bacterial pathogens because it contributes to virulence. In contrast, siderophore-mediated iron acquisition by saprophytic bacteria has received relatively little attention. The independent identification of the des and cch gene clusters that direct production of the tris-hydroxamate ferric iron-chelators desferrioxamine E and coelichelin, respectively, which could potentially act as siderophores in the saprophyte Streptomyces coelicolor A3(2), has recently been reported. Here it is shown that the des cluster also directs production of desferrioxamine B in S. coelicolor and that very similar des and cch clusters direct production of desferrioxamines E and B, and coelichelin, respectively, in Streptomyces ambofaciens ATCC 23877. Sequence analyses of the des and cch clusters suggest that components of ferric-siderophore uptake systems are also encoded within each cluster. The construction and analysis of a series of mutants of S. coelicolor lacking just biosynthetic genes or both the biosynthetic and siderophore uptake genes from the des and cch clusters demonstrated that coelichelin and desferrioxamines E and B all function as siderophores in this organism and that at least one of these metabolites is required for growth under defined conditions even in the presence of significant quantities of ferric iron. These experiments also demonstrated that a third siderophore uptake system must be present in S. coelicolor, in addition to the two encoded within the cch and des clusters, which show selectivity for coelichelin and desferrioxamine E, respectively. The ability of the S. coelicolor mutants to utilize a range of exogenous xenosiderophores for iron acquisition was also examined, showing that the third siderophore-iron transport system has broad specificity for tris-hydroxamate-containing siderophores. Together, these results define a complex system of multiple biosynthetic and uptake pathways for siderophore-mediated iron acquisition in S. coelicolor and S. ambofaciens.

Mining microbial genomes for new natural products and biosynthetic pathways

“…While both the single mutants could grow on this medium provided ferric iron was added, the double mutant could not, even in the presence of high concentrations of ferric iron (Barona-Gó mez et al, 2006). Addition of purified ferrioxamines or ferricoelichelin to the double mutant restored growth (Barona-Gó mez et al, 2006). These data strongly suggest that both desferrioxamines and coelichelin function as siderophores that mediate iron uptake in S. coelicolor.…”

“…7; Barona-Gó mez et al, 2006;Günter et al, 1993). The ferrous complexes of such repressor proteins bind to the inverted repeats and prevent expression of the adjacent genes.…”

“…Conversely the desD mutant did not produce desferrioxamines (Barona-Gó mez et al, 2004), but still made coelichelin (Barona-Gó mez et al, 2006). We also constructed a mutant lacking both the cchH and desD genes, which did not produce coelichelin or desferrioxamines (Barona-Gó mez et al, 2006). The ability of these mutants to grow on a colloidal silica medium was examined.…”

Altered desferrioxamine-mediated iron utilization is a common trait of bald mutants of Streptomyces coelicolor

“…16 This medium is therefore considered iron-limited and, indeed, we recently showed that it strongly stimulates the production of the siderophores coelichelin (CCLIN) and desferrioxamines (DFO). 17 In order to assess the importance of the different types of siderophores for the growth of S. coelicolor on R2YE medium, we compared the growth of S. coelicolor M145 (wild-type) and that of its mutants W4 (DcchH), 18 and JMG1 (DdesA) 19 which are unable to produce CCLIN and DFO, respectively. Fig.…”

Pseudomonas fluorescens Pirates both Ferrioxamine and Ferricoelichelin Siderophores from Streptomyces ambofaciens

“…ambofaciens ATCC 23877 expresses genes necessary for desferrioxamine and coelichelin production on 26A medium. S. ambofaciens ATCC 23877 produces two types of tris-hydroxamate siderophores: desferrioxamine (B and E) and coelichelin (37). We hypothesized that S. ambofaciens produces these siderophores when grown on 26A agar medium and that the siderophores would then be accessible to strain BBc6R8.…”