Prof. Dr. G. Winkelmann
We study the production of microbial (secondary) metabolites that function either as growth inhibitors (antibiotics) or growth promoters (siderophores). We have made major contributions to the identification of novel antifungal antibiotics such as Iturin AL, Herbicolin A and B, and Maltophilin.
Among the growth promotion compounds, the siderophores have received much attention in the scientific community due both to the major progress that have been made during recent years and the ever increasing number of laboratories involved. Some of the commonly found microbial siderophores are shown below.
We also have identified a variety of novel siderophores like ornibactins, rhizoferrins, heterobactins and salmochelins.
Iron transport in fungi and bacteria is a crucial event during growth and development in natural environments and also in the pathophysiology of host-adapted strains. Most of the currently known microbial organisms biosynthesize siderophores (microbial iron chelates) that solubilize and transport environmental iron into the cells during aerobic growth. A major topic of my laboratory has been the isolation of new siderophores and the analysis of their transport properties (see enclosed publication list). Thus we isolated ferrichromes from a variety of acomycetous fungi, including Neurospora crassa, Aspergillus, Penicillium, and Botrytis etc. as well as from mycorhizal fungi. Further we have reported the existence of ferrioxamines in the enterobacterial genera of Erwinia-Enterobacter-Hafnia group and characterized the structurally novel ornibactins in Burkholderia cepacia. Recently, together with Carl J. Carrano, we have isolated and structurally characterized the novel heterobactins in the Rhodococci
In 1991 we identified novel carboxylate-type siderophores, named rhizoferrins, from the fungus Rhizopus and related Mucorales and showed that fungi of the Zygomycetes produce carboxylate siderophores instead of the commonly found hydroxamate siderophores.
R,R-Rhizoferrin isolated from Rhizopus strains (Mucorales, Zygomycetes)
(Drechsel et al., Rhizoferrin - a novel siderophore from the fungus Rhizopus microsporus var. rhizopodiformis. BioMetals 4: 238-243 (1991)
Recently we identified the salmochelins produced by Salmonella enterica and uropathogenic Escherichia coli (UPEC) strains.
Salmochelin S4 isolatzed from S. enterica.
Bister et al. The structure of salmochelins: C-glucosylated enterobactins of Salmonella enterica. BioMetals 17, 471-481, 2004.
In addition to the isolation and characterization of new siderophores we have also investigated the structural details that determine the transport and utilization of the siderophores in fungi and bacteria. Therefore, the specificity of siderophore transport is a major thrust of my laboratory. For example, in 1979 we were the first to demonstrate a pronounced stereoselective uptake of ferrichrome-type siderophores in fungi that is based on stereospecific interaction of membrane located transport proteins. Also the fungal R,R-rhizoferrins and the bacterial S,S-rhizoferrins revealed stereospecific recognition.
Siderophore transporters in Yeast
Currently our siderophore research is focussed on the identification and characterization of siderophore transporters in yeast, where members of the Major Facilitator Superfamily (MFS) are involved in siderophore transport. Thus, we have assigned several MFS-genes of the previously unknown MFS a function in the transport of siderophores, i.e. TAF1 encodes the transporter for triacetylfusarinine C, ARN1 encodes the transporter for ferrichromes carrying anhydro-mevalonyl residues and ENB1 encodes a transporter for enterobactin. Details are summarized in a recent book on Microbial Transport Systems, Wiley-VCH 2001, G. Winkelmann (ed.). We hope to find similar genes in filamentous fungi, although we are only at the beginning of a detailed understanding of siderophore transport and mechanisms in the microbial world.
MFS-Genes involved in Siderophore Transport (Yeast).
Winkelmann, G. Siderophore transport in fungi. In: Microbial Transport Systems (G. Winkelmann, ed.) Wiley-VCH 2001