Microbial iron transport, studies

Anguibactin (470) is a unique siderophore (microbial iron-transport compound) isolated from iron-deficient cultures of a fish pathogenic bacterium, Vibrio anguillarum (378). The structure of 470 was determined by X-ray diffraction studies of its anhydro derivative. Another related compound copurified with 470 was identified as 2-(2, 3 -dihydroxyphenyl)-thiazoline-4-carboxyiic acid methyl ester (471) (379). 

Kinetically Inert Complexes of the Siderophores in Studies of Microbial Iron Transport... 

HPhe preceding and following chapters amply illustrate the reasons why microbial iron transport compounds are worthy of our attention—both from the biochemical and medical points of view. However, one might wonder what this has to do with coordination chemistry. The obvious answer is that these are, after all, coordination compounds. But more than that, when viewed from the perspective of a coordination chemistry, new experiments or new approaches suggest themselves. This is always the exciting potential of interdisciplinary research. This chapter is the result of a research project which has involved extensive collaboration between J. B. Neilands laboratories and my own. Many of the details of the transport studies of kinetically inert, metal-substituted siderophores in... 

The chromic-substituted siderophores can be used to study the mechanisms of microbial iron transport. These studies rely on the kinetic inertness of the chromic complex and would be impossible to carry out using other techniques or probes. 

Hydroxamates and their monothio and dithio analogues form chelate complexes usually. They have been much studied because hydroxamates are present in sidero-phores, the microbial iron transport systems (Section 17-E-10) and also because of their use in sequestering agents for actinide ions and in analytical studies. 

Despite the increase in our understanding of microbial iron transport from these studies, much remains unknown. For example, one of our original queries remains unanswered. Is recognition of the iron(III) siderophore complex and subsequent active transport into the cell dependent on one optical isomer This and other questions concerning the coordination chemistry of sidero-phores remain to be answered. 

Some natural antibiotics contain a siderophore structure, for instance, 5i-albomycin 35, which is produced by Streptomyces subtropicus. The linear tripeptide portion chelates Fe(III) and, thereby, is able to utilize the iron-transport system of a range of microorganisms. Subsequent to uptake, peptidases localized in the cytoplasmic membrane hydrolytically release the toxic thioribosyl moiety. In principle, this property can be used for selective drug delivery. Preliminary studies indicated that substantial modification of the siderophore framework can be tolerated by microbial iron-transport systems. Surprisingly, simple modifications can be made to cephalosporin molecules, which endow them with the ability to interact with microorganism iron-transport mechanisms. Thus, simple incorporation of a catechol moiety, as in 36, endows this molecule with enhanced activity against Pseudomonas aeruginosa when compared... 

Proton-coupled electron transfer (PCET) is known to play an important role in a variety of biological processes, including microbial iron transport by ferric enterobactin, enzyme catalysis in systems such as fumarate reductase and nitrate reducatase, and dioxygen binding by the non-heme iron protein hemerythrin. " As such, pH-dependent electrochemical studies can play an important role in unraveling these mechanisms. The most heavily studied biological system known to involve PCET is cytochrome c oxidase, the terminal electron-transfer complex of the mitochondrial respiratory chain, which catalyzes the reduction of molecular oxygen to water. ... 

Chromium(III) complexes of a number of polyhydroxamic acids, microbial iron sequestering and transport agents (siderochromes) have been reported.797,798 The kinetic inertness of the chromium(III) complexes allows the facile separation of isomers for the model complex tris(iV-methyl-( - )-methoxyacetylhydroxamato)chromium(III), D-cis, L-cis and the l/d-trans isomers have been separated.798 The chromium complexes of desferrioxamine B (191) have been investigated the possible isomers are illustrated below (192-196). The cis isomer was isolated in relatively pure form.799 Thiohydroxamate800 and dihydroxamate (rhodotorulic acid) complexes have also been studied.801... 

Ga was preferred [115] as a substitute for Fe to study metal binding to enterobactin (11), the microbial high-affinity iron transport compound, to retain coupling constant information which is blotted out by the line-broadening, paramagnetic Fe. ... 

The source of phosphorus for incorporation into CFA in the early diagenetic regime is solid-phase phosphorus liberated either by microbial mineralization of organic matter, or by release of phosphorus associated with iron oxyhydroxides upon reduction of the iron oxyhydroxide substrate once it is transported into suboxic or anoxic zones within sediments. Examination of SEDEX-generated phosphorus profiles from a number of studies show roughly mirror-image profiles of the... 

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