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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites MAYBE down
12/28 - 12/31
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MetaCyc Pathway: achromobactin biosynthesis

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Biosynthesis Siderophore Biosynthesis

Some taxa known to possess this pathway include ? : Dickeya dadantii 3937 , Erwinia chrysanthemi , Pseudomonas syringae pv. syringae B728a

Expected Taxonomic Range: Proteobacteria

Summary:
General Background

Iron is an essential micronutrient for most microorganisms. It is a cofactor required for growth and metabolism. However, it is present in the environment as relatively insoluble ferric oxyhydroxide complexes that are not readily bioavailable. Siderophores are high-affinity ferric iron (Fe3+) chelators secreted by microorganisms as a means to access this iron. Bacterial pathogens also utilize siderophores to scavenge tightly bound iron from their hosts. Secreted siderophores solubilize and bind ferric iron. The ferric iron-siderophore complex binds to cell surface receptors and is actively transported into the cell (in [Berti09a] and in [Schmelz09]). In Gram-negative bacteria, the binding protein transports the ferric-siderophore into the periplasm, where a second transporter transports it into the cytosol [Winkelmann02].

There are two general pathways for siderophore biosynthesis. One is the nonribosomal peptide synthetase (NRPS) dependent pathway that is based on the well characterized NRPS multienzyme superfamily. The other is the NRPS-independent pathway, referred to as the NIS pathway. The NIS pathway utilizes a novel superfamily of NIS synthetases that are only beginning to be characterized. Unlike NRPS pathways, NIS pathways involve individual enzymes and free intermediates. NIS synthetases catalyze the condensation of carboxylic acids with amines and alcohols. NIS synthetases are divided into three subfamilies A, B and C based on their carboxylic acid substrate specificities. Type A utilizes citrate, type B utilizes 2-oxoglutarate (α-ketoglutarate) and type C utilizes monoamide or monoester derivatives of citrate, or a monohydroxamate derivative of succinate (in [Schmelz09]).

Genes encoding NIS synthetases have been identified in over 40 species of bacteria. These genes are associated with the production of at least eight distinct siderophores (in [Berti09a]). In addition to the biosynthetic pathway for achromobactin [Berti09a] (this pathway), the biosynthetic pathways for the siderophores staphyloferrin A and staphyloferrin B in Staphylococcus aureus have recently been elucidated [Cheung09, Beasley09, Cotton09].

About This Pathway

This pathway is a proposed NIS (NRPS-independent) pathway for biosynthesis of achromobactin, a siderophore secreted by the plant pathogens Pseudomonas syringae pv. syringae B728a and Dickeya dadantii strain 3937 (also named Erwinia chrysanthemi strain 3937 or Pectobacterium chrysanthemi strain 3937 [Franza05, McMahon08, Schmelz09]). These two organisms are evolutionarily and pathologically distinct from each other. achromobactin has a role as a virulence factor in these organisms (in [Schmelz09]). This pathway has been studied in both Pseudomonas syringae pv. syringae B728a [Berti09a] and Dickeya dadantii 3937 [Franza05, Schmelz09].

Dickeya dadantii 3937 synthesizes the siderophores chrysobactin and achromobactin in response to iron limitation. In Dickeya dadantii 3937 the genes involved in achromobactin biosynthesis have been identified [Franza05]. Biochemical analysis suggested that the product of the AcsD catalyzed reaction is O-citryl-L-serine [Schmelz09]. However, the roles of AcsE, AcsC and AcsA in Dickeya dadantii 3937 remain to be experimentally characterized. The putative pyridoxal 5'-phosphate-dependent decarboxylase product of AcsE could catalyze the formation of O-citryl-ethanolamine. AcsC was proposed to catalyze the synthesis of diaminobutyryl-citryl-ethanolamine. AcsA was proposed to catalyze the successive addition of two 2-oxoglutarate (α-ketoglutarate) moieties to produce achromobactin (in [Berti09a] in [Schmelz09] and reviewed in [Challis05]). It has been shown that the 2-oxoglutarate (α-ketoglutarate) moieties of achromobactin cyclize in neutral aqueous solution to form pyrrolidine rings [Munzinger00] and in [Berti09a].

In Pseudomonas syringae pv. syringae B728a mutant analysis showed that this organism produces both achromobactin and a pyoverdine) siderophores under iron-limited conditions. Recombinant NIS synthetases AcsA, AcsC and AcsD from Pseudomonas syringae pv. syringae B728a were expressed in Escherichia coli, purified and kinetically characterized. A minimal achromobactin synthetase was reconstituted in vitro using these three proteins. Active achromobactin analogs could also be produced using this in vitro system [Berti09a].

Credits:
Created 12-Aug-2010 by Fulcher CA , SRI International


References

Beasley09: Beasley FC, Vines ED, Grigg JC, Zheng Q, Liu S, Lajoie GA, Murphy ME, Heinrichs DE (2009). "Characterization of staphyloferrin A biosynthetic and transport mutants in Staphylococcus aureus." Mol Microbiol 72(4);947-63. PMID: 19400778

Berti09a: Berti AD, Thomas MG (2009). "Analysis of achromobactin biosynthesis by Pseudomonas syringae pv. syringae B728a." J Bacteriol 191(14);4594-604. PMID: 19482931

Challis05: Challis GL (2005). "A widely distributed bacterial pathway for siderophore biosynthesis independent of nonribosomal peptide synthetases." Chembiochem 6(4);601-11. PMID: 15719346

Cheung09: Cheung J, Beasley FC, Liu S, Lajoie GA, Heinrichs DE (2009). "Molecular characterization of staphyloferrin B biosynthesis in Staphylococcus aureus." Mol Microbiol 74(3);594-608. PMID: 19775248

Cotton09: Cotton JL, Tao J, Balibar CJ (2009). "Identification and characterization of the Staphylococcus aureus gene cluster coding for staphyloferrin A." Biochemistry 48(5);1025-35. PMID: 19138128

Franza05: Franza T, Mahe B, Expert D (2005). "Erwinia chrysanthemi requires a second iron transport route dependent of the siderophore achromobactin for extracellular growth and plant infection." Mol Microbiol 55(1);261-75. PMID: 15612933

McMahon08: McMahon SA, Oke M, Liu H, Johnson KA, Carter L, Kadi N, White MF, Challis GL, Naismith JH (2008). "Purification, crystallization and data collection of Pectobacterium chrysanthemi AcsD, a type A siderophore synthetase." Acta Crystallogr Sect F Struct Biol Cryst Commun 64(Pt 11);1052-5. PMID: 18997340

Munzinger00: Munzinger M, Budzikiewicz H, Expert D, Enard C, Meyer JM (2000). "Achromobactin, a new citrate siderophore of Erwinia chrysanthemi." Z Naturforsch C 55(5-6);328-32. PMID: 10928541

Schmelz09: Schmelz S, Kadi N, McMahon SA, Song L, Oves-Costales D, Oke M, Liu H, Johnson KA, Carter LG, Botting CH, White MF, Challis GL, Naismith JH (2009). "AcsD catalyzes enantioselective citrate desymmetrization in siderophore biosynthesis." Nat Chem Biol 5(3);174-82. PMID: 19182782

Visca07: Visca P, Imperi F, Lamont IL (2007). "Pyoverdine siderophores: from biogenesis to biosignificance." Trends Microbiol 15(1);22-30. PMID: 17118662

Winkelmann02: Winkelmann G (2002). "Microbial siderophore-mediated transport." Biochem Soc Trans 30(4);691-6. PMID: 12196166

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Feil05: Feil H, Feil WS, Chain P, Larimer F, DiBartolo G, Copeland A, Lykidis A, Trong S, Nolan M, Goltsman E, Thiel J, Malfatti S, Loper JE, Lapidus A, Detter JC, Land M, Richardson PM, Kyrpides NC, Ivanova N, Lindow SE (2005). "Comparison of the complete genome sequences of Pseudomonas syringae pv. syringae B728a and pv. tomato DC3000." Proc Natl Acad Sci U S A 102(31);11064-9. PMID: 16043691

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 27, 2014, biocyc11.