Iron acquisition in plague: modular logic in enzymatic biogenesis of yersiniabactin by Yersinia pestis
| Autor: | Christopher T. Walsh, Jacqueline D. Fetherston, Robert D. Perry, Edward DeMoll, Ichiro Mori, George F. Mayhew, Frederick R. Blattner, Amy M. Gehring |
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| Rok vydání: | 1998 |
| Předmět: |
siderophore
Sequence analysis Yersinia pestis Iron polyketide synthase Molecular Sequence Data Clinical Biochemistry Siderophores Yersinia Yersiniabactin Biochemistry chemistry.chemical_compound Biosynthesis Bacterial Proteins Phenols Nonribosomal peptide Multienzyme Complexes Polyketide synthase Iron-Binding Proteins Drug Discovery Amino Acid Sequence Molecular Biology DNA Primers chemistry.chemical_classification Pharmacology Plague biology Base Sequence Sequence Homology Amino Acid Virulence heterocyclization yersiniabactin General Medicine biology.organism_classification Acyl carrier protein Thiazoles chemistry Periplasmic Binding Proteins Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization biology.protein Molecular Medicine Salicylic Acid nonribosomal peptide synthetase Bacterial Outer Membrane Proteins |
| Zdroj: | Chemistry & Biology. 5(10):573-586 |
| ISSN: | 1074-5521 |
| DOI: | 10.1016/s1074-5521(98)90115-6 |
| Popis: | Background: Virulence in the pathogenic bacterium Yersinia pestis , causative agent of bubonic plague, has been correlated with the biosynthesis and transport of an iron-chelating siderophore, yersiniabactin, which is induced under iron-starvation conditions. Initial DNA sequencing suggested that this system is highly conserved among the pathogenic Yersinia . Yersiniabactin contains a phenolic group and three five-membered thiazole heterocycles that serve as iron ligands. Results: The entire Y. pestis yersiniabactin region has been sequenced. Sequence analysis of yersiniabactin biosynthetic regions ( irp2-ybtE and ybtS ) reveals a strategy for siderophore production using a mixed polyketide synthase/nonribosomal peptide synthetase complex formed between HMWP1 and HMWP2 (encoded by irp1 and irp2 ). The complex contains 16 domains, five of them variants of phosphopantetheine-modified peptidyl carrier protein or acyl carrier protein domains. HMWP1 and HMWP2 also contain methyltransferase and heterocyclization domains. Mutating ybtS revealed that this gene encodes a protein essential for yersiniabactin synthesis. Conclusions: The HMWP1 and HMWP2 domain organization suggests that the yersiniabactin siderophore is assembled in a modular fashion, in which a series of covalent intermediates are passed from the amino terminus of HMWP2 to the carboxyl terminus of HMWP1. Biosynthetic labeling studies indicate that the three yersiniabactin methyl moieties are donated by S -adenosylmethionine and that the linker between the thiazoline and thiazolidine rings is derived from malonyl-CoA. The salicylate moiety is probably synthesized using the aromatic amino-acid biosynthetic pathway, the final step of which converts chorismate to salicylate. YbtS might be necessary for converting chorismate to salicylate. |
| Databáze: | OpenAIRE |
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