Siderophore enterobactin, catechol-containing

The Catechol-Containing Siderophore—Enterobactin. The isolation and characterization of the cyclic triester 2,3-dihydroxy-N-benzoyl-Z-serine, a tricatechol siderophore (Figure 4), were independently reported by both Pollack and Neilands (18) and O Brien and Gibson (19). The ligand was isolated from cultures of Salmonella typhimurium and Escherichia coli and given the names enterobactin and enterochelin, respectively. Enterobactin is an efficient cellular transport agent but, unlike ferrichrome, intracellular release of the iron involves enzymatic hydrolysis of the enterobactin to the monomer, 2,3-dihydroxy-N-benzoyl-Z-ser-ine (1). 

There are two catecholate siderophores which may be chosen as model compounds for synthesis the cyclic enterobactin and the linear parabactin precursor N. N8-bis(2,3-dihydroxybenzoyl)spermidine. Both of these natural products are capable of the rapid removal of iron from transferrin, the human iron transport protein 89-90). The synthesis of these and other catecholate ligands routinely requires protection of the phenolic oxygens (for example, by methyl, benzyl or acetyl groups). Very few preparations of catechol-containing siderophores have appeared in which the unprotected 2,3-dihydroxybenzoyl group is used in the synthesis 91,92). 

The effective molarity measured for [Phen2]PAAcPEI may be compared with that for enterobactin, the strongest microbial siderophore, containing three catechol units connected by a spacer. The effective molarity of a catechol unit towards a Fe(m) ion bound to another catechol unit contained in enterobactin is estimated to be 3 x 104 m [37]. Enterobactin contains three catechol units, whereas the Cu(ii) binding site of [Phen2]-paAcPEI consists of only two phenanthrolines. Nevertheless, the effective molarity observed for [Phen2]PAAcPEI is extraordinary for a synthetic system. 

The three catechol groups of enterobactin are carried on a cyclic serine triester structure. A variety of both cyclic and linear structures are found among other catechol siderophores. " For example, parabactin and agrobactin (Fig. 16-1) contain a backbone of spermidine (Chapter 24). After the Fe -enterobactin complex enters a bacterial cell the ester linkages of a siderophore are cleaved by an esterase. Because of the extremely high formation constant of M for... 

Althou we have characterized the siderophore of P. denitri-ficans as parabactin (Figure 2, R=H) and not parabactin A (Figure 1, R=H), there is some question as to which form was isolated from the same organism by Tait ( 5 ) The relative stability of the oxazoline to acid hydrolysis, the spectral shifts observed by Tait in acidic media and not found in our parabactin A ( 8), and the properties he ascribes to the iron complex can only be reconciled with the structure in Figure 2, R H. Although crude preparations of ferric enterobactin contain a number of colored species, the reddish form is the tris-catecholate bluish tints are associated with oxidized/polymerized or otherwise coordinated forms of iron ( 23). Parabactin A yields a relatively inferior complex with ferric ion which fails to develop a red color even at quite alkaline pH. 

Many siderophores are three-armed podands that contain hydroxamates or catechol moieties which bind to the metal ion. Siderophore iron(iii) complexes are high-spin and are highly thermodynamically stable. The highest stability constant for a natural siderophore is for enterobactin (2.43), whose affinity for iron(iii) is 10 M h The iron(iii) ion is totally enveloped by the catechol arms in a six-coordinate geometry (2.43). Artificial, macrobicyclic siderophores have achieved binding constants of up to... 

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