BackgroundHuntington's disease (HD) is a fatal inherited neurodegenerative disease, caused by a

Rhizobactin 1021, a novel siderophore from the nitrogen-fixing alfalfa symbiont Rhizobium meliloti 1021, was isolated and structurally characterized by a combination of chemical and spectroscopic techniques. The compound is a citrate derivative in which the distal carboxyl groups of the molecule are amide linked to two different side chains.One of these is 1 -amino-3-(N-hydroxy-N-acetylamino)propane, and the other is l-amino-3-(N-hydroxy-N-(E)-2-deceny1amino)propane. The structure of rhizobactin 1021 was determined as (E)-4-[ [3-(acetylhydroxyamino)propyl]amino]-2-hydroxy-2-[2-[ 3-[hydroxy( 1-oxo-2-decenyl)amino]propyl]amino]-2-oxoethyl]-4-oxobutanoic acid. Ferric rhizobactin 1021 exists in solution predominantly in the A configuration, in an apparent equilibrium between a monomeric and a dimeric species.Iron is essential for virtually all forms of life, and microorganisms have evolved elaborate and tightly regulated systems for its uptake. These systems are compatible with the extremely low solubility of polymeric ferric oxyhydroxides at neutral pH in an oxidizing atmosphere (Ks = 10-38, [Fe3+] = I W 7 M) and the ability of iron ions to catalyze radical-producing reactions.1.2 The extracellular components of these high-affinity iron acquisition systems are known as siderophores, Fe(II1)-specific ligands that are excreted and, upon chelation, diffuse back to the cell surface and reenter the cell via outer membrane ferric siderophore receptor^.^ In host-dependent environments, microorganisms face the additional obstacle of iron-withholding mechanisms$ for endosymbiontic rhizobia, part of the life cycle involves invasion, growth, and differentiation within plant tissue.5Rhizobium meliloti is an endosymbiont of Medicago sativa (alfalfa) and, like other rhizobia, induces nodule formation in the root cortex of its legume host.5 Dinitrogen fixation is catalyzed by bacteroids in the nodules, and since both nitrogenase and leghemoglobin,s as well as regulatory proteins related to nitrogen fixation: contain iron, a satisfactory supply of this element is essential.'The hexadentate siderophore rhizobactin, a complexone type compound from R . meliloti DM-4, has been structurally char-' Present address:

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In response to iron limitation. Pseudomonas fluorescens M114 induces a number of genes including an iron-scavenging siderophore termed pseudobactin M114, its cognate receptor, PbuA, and a casein protease. A Tn5lacZ-induced mutant (M114FA1) was isolated that exhibits a pleiotropic phenotype and lacks the ability to express these iron-regulated genes. A cosmid clone was identified which complements this mutation. This clone is capable of activating a number of iron-regulated promoter fusion constructs from P. fluorescens M114 and Pseudomonas putida WCS358 and can also promote expression of these fusions in Escherichia coli. A series of insertion mutants was constructed by homologous recombination which were unable to transcribe the promoter fusions. DNA sequence analysis of the complementing region identified one open reading frame (ORF) termed pbrA (pseudobactin regulation activation) and the deduced amino acid sequence shows domains with significant homology to a number of ECF (extracytoplasmic function) transcriptional regulators of the sigma 70 sigma factor family, including fecl required for expression of the ferric dicitrate outer-membrane receptor protein of E. coli. Sequences upstream of the pbrA gene suggest that transcription of pbrA may also be iron regulated.