title: 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.
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Francisco
authors.initials: F
authors.lastname: Barona-Gómez
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lautru
authors.affiliation: CNRS, Institut de Génétique et Microbiologie, UMR 8621, Université Paris-Sud 11, 91405 Orsay Cedex, France.
authors.forename: Francois-Xavier
authors.initials: FX
authors.lastname: Francou
authors.affiliation: Laboratoire de Génétique et Microbiologie, UMR INRA 1128 IFR 110, Faculté des Sciences et Techniques, Université Henri Poincaré Nancy 1, Boulevard des Aiguillettes, BP239, 54506 Vandoeuvre-les-Nancy Cedex, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Leblond
authors.affiliation: CNRS, Institut de Génétique et Microbiologie, UMR 8621, Université Paris-Sud 11, 91405 Orsay Cedex, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Pernodet
authors.affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Gregory L
authors.initials: GL
authors.lastname: Challis
mesh_terms: D003676:Deferoxamine / Q000737:chemistry / Q000378:metabolism; D005798:Genes, Bacterial; D007501:Iron / Q000378:metabolism*; D005810:Multigene Family; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism; D017262:Siderophores / Q000235:genetics* / Q000378:metabolism; D013302:Streptomyces / Q000235:genetics* / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000235:genetics / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D017262:Siderophores; C412862:coelichelin; D007501:Iron; D003676:Deferoxamine