Enzymatic logic of anthrax stealth siderophore biosynthesis: AsbA catalyzes ATP-Dependent condensation of citric acid and spermidine
Oves-Costales, Daniel, Kadi, Nadia, Fogg, Mark J., Song, Lijiang, Wilson, Keith S. and Challis, Gregory L.. (2007) Enzymatic logic of anthrax stealth siderophore biosynthesis: AsbA catalyzes ATP-Dependent condensation of citric acid and spermidine. Journal of the American Chemical Society, Vol.129 (No.27). pp. 8416-8417. ISSN 0002-7863Full text not available from this repository.
Official URL: http://dx.doi.org/10.1021/ja072391o
Petrobactin is an iron-chelating siderophore originally isolated from Marinobacter hydrocarbonoclasticus that has been shown to play an important role in growth under iron-deficient conditions and virulence of the deadly bioterrorism agent Bacillus anthracis. It has recently been shown not to bind to siderocalin, leading it to be designated as a "stealth siderophore" that can avoid the mammalian immune system. A unique combination of nonribosomal peptide synthetase (NRPS) and NRPS-independent siderophore (NIS) synthetase enzymes is known to be required for petrobactin biosynthesis in B. anthracis. Here it is shown that AsbA from B. anthracis, the first type A NIS synthetase to be biochemically characterized, catalyzes ATP-dependent regioselective condensation of citric acid with N-8 of spermidine, but not with N-1-(3,4-dihydroxybenzoyl)-spermidine. These results rule out a recently proposed pathway for petrobactin biosynthesis involving AsbA-catalyzed condensation of N-1-(3,4-dihydroxybenzoyl)-spermidine with citric acid and show that acylation of N-1 of spermidine with the 3,4-dihydroxybenzoyl group must occur after acylation of N-8 of spermidine with citrate. They also provide the fundamental knowledge needed to establish a high throughput screen for inhibitors of AsbA that may provide the basis for development of new antibiotics for the treatment of deadly anthrax infections.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry|
|Divisions:||Faculty of Science > Chemistry|
|Journal or Publication Title:||Journal of the American Chemical Society|
|Publisher:||American Chemical Society|
|Official Date:||11 July 2007|
|Number of Pages:||2|
|Page Range:||pp. 8416-8417|
|Access rights to Published version:||Restricted or Subscription Access|
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