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Escherichia coli K-12 substr. MG1655 Pathway: 2,3-dihydroxybenzoate biosynthesis

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

Locations of Mapped Genes:

Genetic Regulation Schematic: ?

Superclasses: Biosynthesis Aromatic Compounds Biosynthesis

Summary:
General Background

Iron is an essential trace element. In the presence of oxygen, ferrous iron (Fe2+) is oxidized to ferric iron (Fe3+) which forms insoluble compounds that are not available to bacteria. As a result, the level of physiologically available iron can drop to low levels and become growth-limiting. To survive, many bacteria evolved specialized transport systems for low molecular weight iron chelating compounds called siderophores which form complexes with Fe3+. Amino acid conjugates of 2,3-dihydroxybenzoate make up a major class of siderophores, including enterobactin, bacillibactin and 2,3-dihydroxybenzoylglycine.

E. coli produces only one siderophore, enterobactin which is a cyclic triester of 2,3-dihydroxybenzoylserine. It is transported by the ferric enterobactin / colicin B / colicin D outer membrane porin FepA which imports Fe3+ chelated to enterobactin into the cell. Enterobactin biosynthesis in unnecessary under anaerobic conditions when iron is in the soluble Fe2+ form.

About This Pathway

As indicated in the first the pathway link, 2,3-dihydroxybenzoate is synthesized from chorismate via isochorismate and 2,3-dihydroxy-2,3-dihydrobenzoate. Chorismate is a key intermediate and branch point in the biosynthesis of many aromatic compounds. As shown in the second pathway link, three molecules of 2,3-dihydroxybenzoate are combined with three molecules of L-serine by the enterobactin synthase to form enterobactin. Isochorismate is both a precursor of enterobactin via isochorismate synthase EntC, and a precursor of menaquinol-8 via isochorismate synthase MenF. Menaquinol-8 is required under anaerobic conditions (see pathway 1,4-dihydroxy-2-naphthoate biosynthesis I and subsequent pathway links).

The biosynthesis of 2,3-dihydroxybenzoate from chorismate is catalyzed by three enzymes EntC, EntB, and EntA. EntC catalyzes the conversion of chorismate to isochorismate. The N-terminal isochorismate lyase domain of EntB hydrolyzes the pyruvate group of isochorismate to produce 2,3-dihydro-2,3-dihydroxybenzoate. The conversion of this latter compound to 2,3-dihydroxybenzoate is catalyzed by the EntA dehydrogenase.

Gene ryhB encodes a small RNA that promotes enterobactin biosynthesis via posttranscriptional mechanisms. It is required for normal expression of the entCEBAH transcription unit, and it also represses translation of the cysE encoded serine acetyltransferase thereby allowing L-serine to be used in enterobactin biosynthesis [Salvail10].

Review: Yamashita, S. and S.K. Buchanan (2010) "Solute and Ion Transport: Outer Membrane Pores and Receptors" EcoSal 3.3.1 [ECOSAL]

Superpathways: enterobactin biosynthesis , superpathway of chorismate metabolism

Credits:
Created 25-Apr-2008 by Caspi R , SRI International
Revised 07-Jul-2008 by Keseler I , SRI International
Last-Curated ? 13-Jun-2012 by Fulcher C , SRI International


References

ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Salvail10: Salvail H, Lanthier-Bourbonnais P, Sobota JM, Caza M, Benjamin JA, Mendieta ME, Lepine F, Dozois CM, Imlay J, Masse E (2010). "A small RNA promotes siderophore production through transcriptional and metabolic remodeling." Proc Natl Acad Sci U S A 107(34);15223-8. PMID: 20696910

Young71: Young IG, Langman L, Luke RK, Gibson F (1971). "Biosynthesis of the iron-transport compound enterochelin: mutants of Escherichia coli unable to synthesize 2,3-dihydroxybenzoate." J Bacteriol 106(1);51-7. PMID: 4928016

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

BRENDA14: BRENDA team (2014). "Imported from BRENDA version existing on Aug 2014." http://www.brenda-enzymes.org.

Chen09: Chen D, Wu R, Bryan TL, Dunaway-Mariano D (2009). "In vitro kinetic analysis of substrate specificity in enterobactin biosynthetic lower pathway enzymes provides insight into the biochemical function of the hot dog-fold thioesterase EntH." Biochemistry 48(3);511-3. PMID: 19119850

Dahm98: Dahm C, Muller R, Schulte G, Schmidt K, Leistner E (1998). "The role of isochorismate hydroxymutase genes entC and menF in enterobactin and menaquinone biosynthesis in Escherichia coli." Biochim Biophys Acta 1425(2);377-86. PMID: 9795253

Daruwala96: Daruwala R, Kwon O, Meganathan R, Hudspeth ME (1996). "A new isochorismate synthase specifically involved in menaquinone (vitamin K2) biosynthesis encoded by the menF gene." FEMS Microbiol Lett 1996;140(2-3);159-63. PMID: 8764478

Daruwala97: Daruwala R, Bhattacharyya DK, Kwon O, Meganathan R (1997). "Menaquinone (vitamin K2) biosynthesis: overexpression, purification, and characterization of a new isochorismate synthase from Escherichia coli." J Bacteriol 1997;179(10);3133-8. PMID: 9150206

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Drake06: Drake EJ, Nicolai DA, Gulick AM (2006). "Structure of the EntB multidomain nonribosomal peptide synthetase and functional analysis of its interaction with the EntE adenylation domain." Chem Biol 13(4);409-19. PMID: 16632253

Gehring97a: Gehring AM, Bradley KA, Walsh CT (1997). "Enterobactin biosynthesis in Escherichia coli: isochorismate lyase (EntB) is a bifunctional enzyme that is phosphopantetheinylated by EntD and then acylated by EntE using ATP and 2,3-dihydroxybenzoate." Biochemistry 1997;36(28);8495-503. PMID: 9214294

Gehring98: Gehring AM, Mori I, Walsh CT (1998). "Reconstitution and characterization of the Escherichia coli enterobactin synthetase from EntB, EntE, and EntF." Biochemistry 1998;37(8);2648-59. PMID: 9485415

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Guo09a: Guo ZF, Sun Y, Zheng S, Guo Z (2009). "Preferential hydrolysis of aberrant intermediates by the type II thioesterase in Escherichia coli nonribosomal enterobactin synthesis: substrate specificities and mutagenic studies on the active-site residues." Biochemistry 48(8);1712-22. PMID: 19193103

Hantash00: Hantash FM, Earhart CF (2000). "Membrane association of the Escherichia coli enterobactin synthase proteins EntB/G, EntE, and EntF." J Bacteriol 182(6);1768-73. PMID: 10692387

Hubrich13: Hubrich F, Mordhorst S, Andexer JN (2013). "Cinnamic acid derivatives as inhibitors for chorismatases and isochorismatases." Bioorg Med Chem Lett 23(5);1477-81. PMID: 23380376

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jiang07: Jiang M, Guo Z (2007). "Effects of macromolecular crowding on the intrinsic catalytic efficiency and structure of enterobactin-specific isochorismate synthase." J Am Chem Soc 129(4);730-1. PMID: 17243787

Khalil09: Khalil S, Pawelek PD (2009). "Ligand-induced conformational rearrangements promote interaction between the Escherichia coli enterobactin biosynthetic proteins EntE and EntB." J Mol Biol 393(3);658-71. PMID: 19699210

Khalil11: Khalil S, Pawelek PD (2011). "Enzymatic adenylation of 2,3-dihydroxybenzoate is enhanced by a protein-protein interaction between Escherichia coli 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase (EntA) and 2,3-dihydroxybenzoate-AMP ligase (EntE)." Biochemistry 50(4);533-45. PMID: 21166461

Koglin09: Koglin A, Walsh CT (2009). "Structural insights into nonribosomal peptide enzymatic assembly lines." Nat Prod Rep 26(8);987-1000. PMID: 19636447

Kolappan07: Kolappan S, Zwahlen J, Zhou R, Truglio JJ, Tonge PJ, Kisker C (2007). "Lysine 190 is the catalytic base in MenF, the menaquinone-specific isochorismate synthase from Escherichia coli: implications for an enzyme family." Biochemistry 46(4);946-53. PMID: 17240978

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Wed Nov 26, 2014, biocyc13.