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

Abstract

Streptomyces coelicolor is an important model organism for developmental studies of filamentous GCrich actinobacteria. The genetic characterization of mutants of S. coelicolor blocked at the vegetative mycelium stage, the so-called bald (bld) mutants that are unable to erect spore-forming aerial hyphae, has opened the way to discovering the molecular basis of development in actinomycetes. Desferrioxamine (DFO) production and import of ferrioxamines (FO; iron-complexed DFO) are key to triggering morphogenesis of S. coelicolor and we show here that growth of S. coelicolor on the reference medium for Streptomyces developmental studies is fully dependent on DFO biosynthesis. UPLC-ESI-MS analysis revealed that all bld mutants tested are affected in DFO biosynthesis, with bldA, bldJ, and ptsH mutants severely impaired in DFO production, while bldF, bldK, crr and ptsI mutants overproduce DFO.Morphogenesis of bldK and bldJ mutants was recovered by supplying exogenous iron. Transcript analysis showed that the bldJ mutant is impaired in expression of genes involved in the uptake of FO, whereas transcription of genes involved in both DFO biosynthesis and FO uptake is increased in bldK mutants. Our study allows proposing altered DFO production and/or FO uptake as a novel phenotypic marker of many S. coelicolor bld mutants, and strengthens the role of siderophores and iron acquisition in morphological development of actinomycetes.

Streptomycesvolatile compounds influence exploration and microbial community dynamics by altering iron availability

“…Transcript levels associated with genes in the desferrioxamine biosynthetic cluster ( sven_2568 and sven_2470/desA ) were higher in the double transporter mutant compared to wild type ( Fig. 5C ), consistent with what has been observed previously for bldK mutants in S. coelicolor (21). In contrast, genes in the other four siderophore-encoding biosynthetic clusters were unaltered in wild type and transporter mutant strains ( Fig.…”

“…The closest characterized homologues to these genes in the model S. coelicolor system were in the bldK locus ( sco5112-16 ). Recent work has suggested that BldK transporters function in ferrioxamine siderophore uptake (21). Increased expression for these two bldK- like transporter gene clusters in S. venezuelae implied that exploring cultures may adapt to alkaline, low-iron environments by coupling increased desferrioxamine production with enhanced ferrioxamine uptake.…”

Multiple allosteric effectors control the affinity of DasR for its target sites

“…'Das' stands for Defect in aerial hyphae and spore formation which refers to the impaired sporulation phenotype exhibited by the dasR null mutants of Streptomyces griseus [7] and Streptomyces coelicolor [2]. The observed developmental defect of dasR mutants fits with a regulon that extends well beyond GlcNAc and chitin utilization genes [8,9], such as gene clusters involved in the production of antibiotics prodiginines and actinorhodin [10] and the desferrioxamine siderophores [11] which are essential for proper sporulation of S. coelicolor [12,13]. The identification of the DasR regulon and the functional characterization of the genes it controls allows the description of the very first complete signalling cascade from extracellular signal transport to the control of secondary metabolite production in the industrially important Streptomyces genus [10].…”

Bagremycin Antibiotics and Ferroverdin iron-chelators are synthetized by the Same Gene Cluster

“…Finally, next to the role of iron as vital element for growth [38,39], morphogenesis and metabolite production [12,39,40], our work reveals an unprecedented complexity of natural product biosynthetic pathways where this element is also an environmental trigger able to change the pattern of natural compounds produced by a single BGC. By challenging the concept that one BGC should produce a single family of molecules, our results also highlight the difficulty to estimate the metabolic potential of an organism based on the genomic information alone.…”