FIGURE 1.

Structure and biosynthesis of petrobactin, the virulence-associated siderophore of Bacillus anthracis. A, petrobactin is a symmetrical, mixed catechol-hydroxy-carboxylate siderophore comprised of a central citric acid moiety, two spermidine arms, and two 3,4-DHBA moieties. The unique 3,4-position of the hydroxyl groups in the catechol confers the stealth characteristics of petrobactin during host infection. B, the asbABCDEF gene cluster, shown with B. anthracis strain Ames labels, encodes the enzymatic machinery required for biosynthesis of petrobactin. Products include NIS synthetases (gray), a nonribosomal peptide synthetase-like aryl transferase system (white), and a 3-dehydroshikimate dehydratase/3,4-DHBA synthase (black). C, shown is the proposed pathway for petrobactin biosynthesis. Left panel, AsbF converts 3-dehydroshikimate to 3,4-DHBA, which is in turn adenylated by AsbC and loaded onto the phosphopantetheine thiol of the aryl-carrier protein AsbD. In vitro, AsbE transfers the 3,4-dihydroxybenzoyl group from AsbD to the primary amino groups of spermidine. Right panel, through regioselective condensation of spermidine with citric acid, AsbA and AsbB form intermediates that subsequently react with 3,4-dihydroxybenzoyl units. The flexibility of AsbB in vitro suggests multiple possible routes for the biosynthesis of petrobactin.