395:(PKS) mechanism. Several enzymes, most notably the HMWP2-HMWP1complex, assemble salicylate, three cysteines, a malonyl linker group and three methyl groups into a four-ring structure made of salicylate, one thiazolidine, and two thiazoline rings with a malonyl linker between the thiazoline and the thiazolidine. YbtD, a phosphopantetheinyl transferase, adds phosphopantetheine tethers to the cysteine, salicylate and malonyl groups to HMWP1 and HMWP2. YbtS synthesizes salicylate from chorismate, which is then adenylated by YbtE and transferred to the HMWP2–HMWP1 assembly complex. HMWP2, which consists of two multidomain NRPS modules, accepts the activated salicylate unit through a carrier protein, then cyclizes and condenses two cysteines to form two
426:
yersiniabactin can solubilize the metal bound to host binding proteins and transport it back to the bacteria. The complex yersiniabactin-Fe recognizes the specific bacterial outer membrane TonB-dependent receptor, FyuA (Psn), and is translocated with the help of membrane-embedded proteins into the cytosol where the iron is discharged from yersiniabactin and used in various metabolic pathways. In the absence of a high-affinity iron-chelating compound, pathogenic
24:
413:
presence of iron. In the presence of Ybt, a member of the AraC family of transcriptional regulators, activates expression from the psn, irp2 and ybtP (transport and biosynthetic genes) promoters but represses expression of its own promoter. There is also evidence that yersiniabactin itself may upregulate its own expression and that of psn/fyuA and ybtPQXS at the transcription level.
430:, responsible for such lethal disease as the bubonic plague, only causes local symptoms of moderate intensity. The availability of iron, through an intrinsic high-affinity iron-chelating system such as Ybt, provides the bacteria with the ability to multiply in the host and to cause systemic infections.
412:
The HPI upon which the genes encoding the Ybt biosynthesis proteins are located is controlled by a series of molecular regulators. All four promoter regions of the yersiniabactin region (psn, irp2, ybtA and ybtP) possess a Fur-binding site and are negatively regulated by this repressor in the
425:
As previously mentioned, siderophores serve the essential function of iron acquisition for pathogens in the low iron conditions of the host. Thus the successful establishment of disease depends on the ability of the invading organism to acquire iron. Because of its high affinity for iron,
403:
before cyclization and condensation of the final thiazoline ring on HMWP1's NRPs domain. YbtT thioesterase may serve some editing function to remove abnormal molecules from the enzyme complex, and a thioesterase domain of HMWP1 releases the completed siderophore from the enzyme complex.
383:, it binds Feas a 1:1 complex by three nitrogen electron pairs and three negatively charged oxygen atoms (each set in meridional positions) with a distorted octahedral structure. The Ybt-Fe complex has a proton-independent formation constant of 4 x 10.
359:; thus, the pathogen produces molecules with an even higher affinity for Fe than these proteins in order to acquire sufficient iron for growth. As a part of such an iron-uptake system, yersiniabactin plays an important role in pathogenicity of
49:
578:
Bisseret, P.; Thielges, S.; Bourg, S. P.; Miethke, M.; Marahiel, M. A.; Eustache, J. (2007). "Synthesis of a 2-indolylphosphonamide derivative with inhibitory activity against yersiniabactin biosynthesis".
177:
InChI=1S/C21H27N3O4S3/c1-20(2,18-24-21(3,10-31-18)19(27)28)15(26)12-8-30-17(22-12)13-9-29-16(23-13)11-6-4-5-7-14(11)25/h4-7,12-13,15,17,22,25-26H,8-10H2,1-3H3,(H,27,28)/t12-,13-,15-,17+,21-/m1/s1
187:
InChI=1/C21H27N3O4S3/c1-20(2,18-24-21(3,10-31-18)19(27)28)15(26)12-8-30-17(22-12)13-9-29-16(23-13)11-6-4-5-7-14(11)25/h4-7,12-13,15,17,22,25-26H,8-10H2,1-3H3,(H,27,28)/t12-,13-,15-,17+,21-/m1/s1
540:
Miller, M. C.; Parkin, S.; Fetherston, J. D.; Perry, R. D.; Demoll, E. (2006). "Crystal structure of ferric-yersiniabactin, a virulence factor of
Yersinia pestis".
759:"Reduced synthesis of the Ybt siderophore or production of aberrant Ybt-like molecules activates transcription of yersiniabactin genes in Yersinia pestis"
203:
501:"Yersiniabactin from Yersinia pestis: Biochemical characterization of the siderophore and its role in iron transport and regulation"
608:"Biosynthesis of Yersiniabactin, a Complex Polyketide-Nonribosomal Peptide, Using Escherichia coli as a Heterologous Host"
168:
287:
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Miller, M. C.; Fetherston, J. D.; Pickett, C. L.; Bobrov, A. G.; Weaver, R. H.; Demoll, E.; Perry, R. D. (2010).
379:
Yersiniabactin is a four ring structure composed of carbon, hydrogen, nitrogen, oxygen, and sulfur. According to
399:
rings. A malonyl linker is added by the PKS portion of HMWP1, and YbtU reduces the second thiazoline ring to
665:"Role of the Yersinia pestis Yersiniabactin Iron Acquisition System in the Incidence of Flea-Borne Plague"
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888:
317:
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Sebbane, F.; Jarrett, C.; Gardner, D.; Long, D.; Hinnebusch, B. J. (2010). Ii, Roy Martin Roop (ed.).
343:. Siderophores, compounds of low molecular mass with high affinities for ferric iron, are important
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in pathogenic bacteria. Iron—an essential element for life used for such cellular processes as
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Carniel, E. (2001). "The
Yersinia high-pathogenicity island: An iron-uptake island".
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Perry, R. D.; Shah, J.; Bearden, S. W.; Thompson, J. M.; Fetherston, J. D. (2003).
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Perry, R. D.; Balbo, P. B.; Jones, H. A.; Fetherston, J. D.; Demoll, E. (1999).
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810:"Yersinia pestis TonB: Role in Iron, Heme, and Hemoprotein Utilization"
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Ybt synthesis occurs by a mixed nonribosomal peptide synthetase (NRPS)/
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Except where otherwise noted, data are given for materials in their
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and DNA replication—is extensively chelated by host proteins like
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Pfeifer, B. A.; Wang, C. C. C.; Walsh, C. T.; Khosla, C. (2003).
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449:"Evolutionary Genomics of Salmonella enterica Subspecies"
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CC(C)((O)1CSC(N1)2CSC(=N2)c3ccccc3O)C4=N(C)(CS4)C(=O)O
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612:Applied and Environmental Microbiology
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375:Structure and coordination properties
180:Key: JHYVWAMMAMCUIR-BKEHUNJYSA-N
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190:Key: JHYVWAMMAMCUIR-BKEHUNJYBK
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542:Journal of Inorganic Biochemistry
327:, as well as several strains of
632:10.1128/AEM.69.11.6698-6702.2003
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826:10.1128/IAI.71.7.4159-4162.2003
554:10.1016/j.jinorgbio.2006.04.007
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284:(at 25 °C , 100 kPa).
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736:10.1016/S1286-4579(01)01412-5
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690:10.1371/journal.pone.0014379
593:10.1016/j.tetlet.2007.06.150
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518:10.1099/13500872-145-5-1181
331:including enteropathogenic
318:Yersinia pseudotuberculosis
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408:Regulation of expression
306:found in the pathogenic
324:Yersinia enterocolitica
814:Infection and Immunity
776:10.1099/mic.0.037945-0
724:Microbes and Infection
465:10.1128/mBio.00579-12
447:Desai, P. T. (2013).
381:X-ray crystallography
365:Y. pseudotuberculosis
681:2010PLoSO...514379S
624:2003ApEnM..69.6698P
581:Tetrahedron Letters
393:polyketide synthase
340:Salmonella enterica
274: g·mol
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889:Secondary alcohols
288:Infobox references
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618:(11): 6698–6702.
345:virulence factors
296:Chemical compound
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50:Interactive image
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31:Identifiers
879:Amino acids
353:lactoferrin
349:respiration
304:siderophore
302:(Ybt) is a
220:Properties
70:CHEBI:29707
858:Categories
434:References
397:thiazoline
267:Molar mass
101:ChemSpider
37:3D model (
869:Thiazoles
361:Y. pestis
844:12819108
795:20413552
744:11418330
709:21179420
669:PLOS ONE
650:14602630
562:16806483
527:10376834
483:23462113
428:Yersinia
419:Yersinia
417:Role in
357:ferritin
308:bacteria
110:34947481
884:Phenols
786:3068685
700:3003698
677:Bibcode
620:Bibcode
474:3604774
142:PubChem
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321:, and
272:481.64
204:SMILES
155:443589
130:C12038
81:ChEMBL
169:InChI
61:ChEBI
39:JSmol
840:PMID
791:PMID
740:PMID
705:PMID
646:PMID
558:PMID
523:PMID
479:PMID
453:mBio
355:and
337:and
121:KEGG
830:PMC
822:doi
781:PMC
771:doi
767:156
732:doi
695:PMC
685:doi
636:PMC
628:doi
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513:doi
509:145
469:PMC
461:doi
145:CID
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