Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store
Updated BioCyc iOS App now
available in iTunes store

MetaCyc Pathway: alcaligin biosynthesis
Traceable author statement to experimental supportInferred from experiment

Enzyme View:

Pathway diagram: alcaligin biosynthesis

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: BiosynthesisSiderophore Biosynthesis

Some taxa known to possess this pathway include : Achromobacter xylosoxidans, Bordetella bronchiseptica, Bordetella parapertussis, Bordetella pertussis

Expected Taxonomic Range: Alcaligenaceae

General Background

Iron is an essential trace element. In the presence of oxygen, ferrous iron is oxidized to ferric iron which forms insoluble compounds, and is thus not available to organisms. As a result, the level of physiologically available iron can drop to far below 1 μM, and become growth-limiting for bacteria. To survive, many bacteria evolved specialized transport systems called siderophores, which can complex and retract ferric iron ions. The siderophores are low molecular mass compounds, and have been generally divided into three main types: catecholate-, hydroxamate-, and carboxylate-siderophores.

The siderophores, which have a very high and specific affinity for Fe3+, are excreted out of the cell and bind the metal extracellularly. The siderophore-metal complex is transported back into the cell through specific binding proteins present in the bacterial membrane. In Gram-negative bacteria, the binding protein transports the ferric-siderophore into the periplasm, where a second transporter transports it into the cytosol [Winkelmann02].

About This Pathway

Alcaligin is a dihydroxamate siderophore that was originally identifed in the marine bacterium Achromobacter xylosoxidans (then known as Alcaligenes denitrificans) [Nishio88]. Alcaligin was subsequently identified as the siderophore of the important pathogens Bordetella pertussis and Bordetella bronchiseptica, previously known as bordetellin [Moore95a].

The alcA gene, which encodes the first enzyme in the pathway, was the first to be identified, by complementation of a Bordetella bronchiseptica transposon mutant defective in alcaligin biosynthesis [Giardina95]. The gene was found to be homologous to the Escherichia coli iucD gene, which is involved in aerobactin biosynthesis. Two additional genes, alcB and alcC, were discovered next to alcA [Giardina97]. These genes were homologous to the aerobactin biosynthetic genes iucB and iucC, respectively. The three genes form an operon whose transcription is regulated by iron [Giardina97]. An identical operon was found in the genome of the related Bordetella pertussis [Kang96a]. Subsequent work revealed three additional genes in the operon. Two tightly linked open reading frames, alcD and alcE, follow alcC, and a third gene, alcR, which encodes a transcriptional regulator, ends the operon [Pradel98, Beaumont98].

The roles of alkD and alcE are not well understood, but a recent review proposed that alcE, which shows significant similarity to Rieske dioxygenases such as naphthalene dioxygenase, may catalyze the hydroxylation of N-hydroxy-N-succinyl-putrescine, yielding 3-[4-amino-3-hydroxybutyl]-hydroxy-carbamoyl-propanoate [Challis05].

Created 13-Nov-2009 by Caspi R, SRI International


Beaumont98: Beaumont FC, Kang HY, Brickman TJ, Armstrong SK (1998). "Identification and characterization of alcR, a gene encoding an AraC-like regulator of alcaligin siderophore biosynthesis and transport in Bordetella pertussis and Bordetella bronchiseptica." J Bacteriol 180(4);862-70. PMID: 9473040

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

Giardina95: Giardina PC, Foster LA, Toth SI, Roe BA, Dyer DW (1995). "Identification of alcA, a Bordetella bronchiseptica gene necessary for alcaligin production." Gene 167(1-2);133-6. PMID: 8566764

Giardina97: Giardina PC, Foster LA, Toth SI, Roe BA, Dyer DW (1997). "Analysis of the alcABC operon encoding alcaligin biosynthesis enzymes in Bordetella bronchiseptica." Gene 194(1);19-24. PMID: 9266668

Kang96a: Kang HY, Brickman TJ, Beaumont FC, Armstrong SK (1996). "Identification and characterization of iron-regulated Bordetella pertussis alcaligin siderophore biosynthesis genes." J Bacteriol 178(16);4877-84. PMID: 8759851

Moore95a: Moore CH, Foster LA, Gerbig DG, Dyer DW, Gibson BW (1995). "Identification of alcaligin as the siderophore produced by Bordetella pertussis and B. bronchiseptica." J Bacteriol 177(4);1116-8. PMID: 7860593

Nishio88: Nishio, T., Tanaka, N., Hiratake, J., Katsube, Y., Ishida, Y., Oda, J. (1988). "Isolation and structure of the novel dihydroxamate siderophore alcaligin." J. Am. Chem. Soc. 110:8733-8734.

Pradel98: Pradel E, Guiso N, Locht C (1998). "Identification of AlcR, an AraC-type regulator of alcaligin siderophore synthesis in Bordetella bronchiseptica and Bordetella pertussis." J Bacteriol 180(4);871-80. PMID: 9473041

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

Kadi08a: Kadi N, Arbache S, Song L, Oves-Costales D, Challis GL (2008). "Identification of a gene cluster that directs putrebactin biosynthesis in Shewanella species: PubC catalyzes cyclodimerization of N-hydroxy-N-succinylputrescine." J Am Chem Soc 130(32);10458-9. PMID: 18630910

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

Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216

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 Pathway Tools version 19.5 (software by SRI International) on Wed May 4, 2016, biocyc13.