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|
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.
Superpathways: pantothenate and coenzyme A biosynthesis I
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
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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
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
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
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
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