Petrobactin

Petrobactin is a bis-catechol siderophore found in M. hydrocarbonoclasticus, A. macleodii, and the anthrax-producing B. anthracis. Like other siderophores petrobactin is a highly specific iron(III) transport ligand, contributing to the marine microbial uptake of environmental iron.

The iron-chelated petrobactin complex readily undergoes a photolytic oxidative decarboxylation due to its α-hydroxy carboxylate group, converting iron(III) to the more biologically useful iron(II).



Biological function
Like other siderophores, petrobactin is secreted by an animal pathogenic bacterium. B. anthracis uses petrobactin to acquire iron from its host. Interestingly, while the 3,4-catecholate ends of petrobactin do not improve iron(III) affinity relative to hydroxamate ends, they speed up iron removal from human diferric transferrin. Petrobactin in its ferric and iron-free forms is bound selectively by YclQ (an isogenic disruption mutant in the transporter encoded by the yclNOPQ operon in Bacillus subtilis), as is petrobactin's precursor protocatechuic acid and the ferric petrobactin photoproduct. The yclNOPQ operon is required for the utlization of petrobactin and yclNOPQ orthologs likely contribute to the pathogenicity of Bacilli.

Biosynthesis
In B. anthracis, petrobactin is produced by a nonribosomal peptide synthetase independent siderophore (NIS) synthetase pathway. The enzyme sequences used are anthrax siderophore biosynthesis (Asb) A through F, in alphabetical order. These gene clusters are identical to those used in M. hydrocarbonclasticus biosynthesis of petrobactin. In A. macleodii only the first three gene clusters, AsbA through AsbC, are identical to B. anthracis; then a longer AsbD and AsbF is next, followed by two hypothetical protein domains and a PepSY domain-containing gene. A. macleodii ends its sequence with AsbE.

The biosynthesis of petrobactin in B. anthracis can progress in order AsbA-AsbB-AsbE-AsbE or AsbA-AsbE-AsbB-AsbE.



If the enzymation reactions in this pathway proceed generally, in domains AsbA and AsbB the phosphorylation of a carboxylic acid forms an acylphosphate intermediate, which is then dephosphorylated by a primary amine in spermidine. In domain AsbE the lone pair of electrons on a primary amine allows for a nucleophilic attack on the electrophilic hydroxyl carbon. The sulfur on AsbE is protonated to form a thiol and the amide nitrogen is deprotonated.

The dehydration of 3-dehydroshikimic acid might proceed as a modified, enzyme-catalyzed dienol benzene rearrangement and reduction, leading to aromatization of the ring.