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Escherichia coli K-12 substr. MG1655 Pathway: coenzyme A biosynthesis I

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

Locations of Mapped Genes:

Synonyms: CoA biosynthesis

Superclasses: Biosynthesis Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis Coenzyme A Biosynthesis

Summary:
General Background

Coenzyme A (CoA) is an essential and ubiquitous cofactor occurring in bacteria, fungi, plants and animals. It is utilized both as a source of the phosphopantetheine moiety of certain proteins and as a carrier in a large number of reactions central to intermediary metabolism. CoA is the acyl carrier required for reactions in both biosynthetic and degradative pathways, forming derivatives that are key intermediates in energy metabolism.

The biosynthesis of CoA was recognized as a target for antibacterial drug discovery. Interest in the human pathway was sparked by the association of a neurodegenerative disorder with mutations in pantothenate kinase.

About This Pathway

Pantothenate is the starting compound for the biosynthesis of CoA. E. coli can synthesize pantothenate via the phosphopantothenate biosynthesis I pathway or import it from the medium via the pantothenate:Na+ symporter. Five enzymatic steps then convert pantothenate to CoA.

Pantothenate kinase first phosphorylates pantothenate to 4'-phosphopantothenate; the enzyme is feedback inhibited by CoA itself, accounting for the primary regulatory mechanism of CoA biosynthesis. The addition of cysteine, resulting in the formation of (R)-4'-phospho-N-pantothenoylcysteine (PPC), and the subsequent decarboxylation of PPC to 4'-phosphopantetheine, are catalyzed by a bifunctional enzyme. The enzymatic activities can be separated, and indeed exist as two separately encoded enzymes in other organisms. Phosphopantetheine adenylyltransferase and dephospho-CoA kinase finally convert 4'-phosphopantetheine to CoA.

All enzymes of this pathway are essential for growth of E. coli.

Reviews: [Leonardi05], Leonardi, R. and Jackowski, S., Biosynthesis of Pantothenic Acid and Coenzyme A, Module 3.6.3.4 [ECOSAL]

Superpathways: pantothenate and coenzyme A biosynthesis I

Credits:
Created 07-Oct-2003 by Arnaud M , SRI International
Reviewed 24-Oct-2006 by Foerster H , TAIR
Revised 12-Jun-2008 by Keseler I , SRI International


References

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

Leonardi05: Leonardi R, Zhang YM, Rock CO, Jackowski S (2005). "Coenzyme A: back in action." Prog Lipid Res 44(2-3);125-53. PMID: 15893380

Vallari87: Vallari DS, Rock CO (1987). "Isolation and characterization of temperature-sensitive pantothenate kinase (coaA) mutants of Escherichia coli." J Bacteriol 169(12);5795-800. PMID: 2824448

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

Badger, 2005: Badger J, Sauder JM, Adams JM, Antonysamy S, Bain K, Bergseid MG, Buchanan SG, Buchanan MD, Batiyenko Y, Christopher JA, Emtage S, Eroshkina A, Feil I, Furlong EB, Gajiwala KS, Gao X, He D, Hendle J, Huber A, Hoda K, Kearins P, Kissinger C, Laubert B, Lewis HA, Lin J, Loomis K, Lorimer D, Louie G, Maletic M, Marsh CD, Miller I, Molinari J, Muller-Dieckmann HJ, Newman JM, Noland BW, Pagarigan B, Park F, Peat TS, Post KW, Radojicic S, Ramos A, Romero R, Rutter ME, Sanderson WE, Schwinn KD, Tresser J, Winhoven J, Wright TA, Wu L, Xu J, Harris TJ (2005). "Structural analysis of a set of proteins resulting from a bacterial genomics project." Proteins 60(4);787-96. PMID: 16021622

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

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

Freiberg, 2001: Freiberg C, Wieland B, Spaltmann F, Ehlert K, Brotz H, Labischinski H (2001). "Identification of novel essential Escherichia coli genes conserved among pathogenic bacteria." J Mol Microbiol Biotechnol 3(3);483-9. PMID: 11361082

Geerlof99: Geerlof A, Lewendon A, Shaw WV (1999). "Purification and characterization of phosphopantetheine adenylyltransferase from Escherichia coli." J Biol Chem 1999;274(38);27105-11. PMID: 10480925

Gerdes02: Gerdes SY, Scholle MD, D'Souza M, Bernal A, Baev MV, Farrell M, Kurnasov OV, Daugherty MD, Mseeh F, Polanuyer BM, Campbell JW, Anantha S, Shatalin KY, Chowdhury SA, Fonstein MY, Osterman AL (2002). "From genetic footprinting to antimicrobial drug targets: examples in cofactor biosynthetic pathways." J Bacteriol 184(16);4555-72. PMID: 12142426

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Hare01: Hare RS, Walker SS, Dorman TE, Greene JR, Guzman LM, Kenney TJ, Sulavik MC, Baradaran K, Houseweart C, Yu H, Foldes Z, Motzer A, Walbridge M, Shimer GH, Shaw KJ (2001). "Genetic footprinting in bacteria." J Bacteriol 183(5);1694-706. PMID: 11160101

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

Izard02: Izard T (2002). "The crystal structures of phosphopantetheine adenylyltransferase with bound substrates reveal the enzyme's catalytic mechanism." J Mol Biol 315(4);487-95. PMID: 11812124

Izard03: Izard T (2003). "A novel adenylate binding site confers phosphopantetheine adenylyltransferase interactions with coenzyme A." J Bacteriol 185(14);4074-80. PMID: 12837781

Izard99: Izard T, Geerlof A, Lewendon A, Barker JJ (1999). "Cubic crystals of phosphopantetheine adenylyltransferase from Escherichia coli." Acta Crystallogr D Biol Crystallogr 1999;55 ( Pt 6);1226-8. PMID: 10329792

Izard99a: Izard T, Geerlof A (1999). "The crystal structure of a novel bacterial adenylyltransferase reveals half of sites reactivity." EMBO J 1999;18(8);2021-30. PMID: 10205156

Jackowski84: Jackowski S, Rock CO (1984). "Metabolism of 4'-phosphopantetheine in Escherichia coli." J Bacteriol 158(1);115-20. PMID: 6370952

Kupke00: Kupke T, Uebele M, Schmid D, Jung G, Blaesse M, Steinbacher S (2000). "Molecular characterization of lantibiotic-synthesizing enzyme EpiD reveals a function for bacterial Dfp proteins in coenzyme A biosynthesis." J Biol Chem 2000;275(41);31838-46. PMID: 10922366

Kupke01: Kupke T (2001). "Molecular characterization of the 4'-phosphopantothenoylcysteine decarboxylase domain of bacterial Dfp flavoproteins." J Biol Chem 2001;276(29);27597-604. PMID: 11358972

Kupke02: Kupke T (2002). "Molecular characterization of the 4'-phosphopantothenoylcysteine synthetase domain of bacterial dfp flavoproteins." J Biol Chem 277(39);36137-45. PMID: 12140293

Kupke04: Kupke T (2004). "Active-site residues and amino acid specificity of the bacterial 4'-phosphopantothenoylcysteine synthetase CoaB." Eur J Biochem 271(1);163-72. PMID: 14686929

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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