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.
Synonyms: vitamin B5 biosynthesis
|Superclasses:||Biosynthesis → Cofactors, Prosthetic Groups, Electron Carriers Biosynthesis → Vitamins Biosynthesis → Pantothenate Biosynthesis|
Some taxa known to possess this pathway include : Arabidopsis thaliana col, Datura inoxia, Escherichia coli K-12 substr. MG1655, Francisella tularensis tularensis SCHU S4, Hordeum vulgare, Lotus japonicus, Saccharomyces cerevisiae
(R)-4'-phosphopantothenate is the universal precursor for the synthesis of the 4'-phosphopantetheine moiety of coenzyme A and acyl carrier protein. Only plants and microorganisms (including some eukaryotic microbes, such as Saccharomyces cerevisiae) can synthesize pantothenate de novo - animals require a dietary supplement. The enzymes of this pathway are therefore considered to be antimicrobial drug targets.
About This Pathway
The starting compound for pantothenate biosynthesis, 3-methyl-2-oxobutanoate, is derived from the L-valine biosynthesis pathway. The first committed step in the pathway is the transfer of a methyl group to 2-keto-isovalerate by 3-methyl-2-oxobutanoate hydroxymethyltransferase. The product of this reaction, 2-dehydropantoate, is subsequently reduced by 2-dehydropantoate 2-reductase to (R)-pantoate. The final step is the ATP hydrolysis-dependent condensation of L-pantoate with β-alanine to form (R)-pantothenate, which is catalyzed by pantothenate synthetase.
The enzymes of this pathway are not essential for viability of Escherichia coli K-12 grown on media supplemented with pantothenate, due to the presence of a transporter for pantothenate, PanF [Jackowski90].
This pathway in Yeast
Three out of the four reactions involved in the conversion of 3-methyl-2-oxobutanoate to the common intermediate towards coenzyme A biosynthesis, i.e. (R)-4'-phosphopantothenate have been associated with enzymes in Saccharomyces cerevisiae. The second reaction in the pathway catalyzed by the 2-dehydropantoate 2-reductase in bacteria is still elusive for yeast and remains to be resolved. Utilizing genetic and biochemical approaches the functions of 3-methyl-2-oxobutanoate hydroxymethyltransferase [White01, Shimoi00, Olzhausen09], pantoate β-alanine ligase [White01, Olzhausen09] and pantothenate kinase [Olzhausen09] have been elucidated and emphasizes the general notion that the pathway sequences of (R)-4'-phosphopantothenate and coenzyme A biosynthesis are almost identical among the various kingdoms.
This Pathway in Plants
Feeding studies in Pisum sativum leaf discs support the existence of a similar biosynthesis pathway of pantothenate via pantoate: when fed with [14C]valine, the radiolabel was incorporated into α-oxoisovalerate, oxopantoate and pantoate [Jones94]. A number of enzymes involved in pantothenate biosynthesis have been characterized from different plants, including the enzyme catalyzing the last step of the pathway: pantothenate synthetase. This enzyme catalyzes the formation of pantothenate from pantoate and β-alanine. The origin of plant β-alanine is uncertain but appears to be different from that of bacteria which synthesize it from L-aspartate. Instead plants seem to produce β-alanine from a variety of other sources, like polyamines, uracil and propionate (see β-alanine biosynthesis II) [Raman04].
Unification Links: EcoCyc:PANTO-PWY
Olzhausen09: Olzhausen J, Schubbe S, Schuller HJ (2009). "Genetic analysis of coenzyme A biosynthesis in the yeast Saccharomyces cerevisiae: identification of a conditional mutation in the pantothenate kinase gene CAB1." Curr Genet 55(2);163-73. PMID: 19266201
Shimoi00: Shimoi H, Okuda M, Ito K (2000). "Molecular cloning and application of a gene complementing pantothenic acid auxotrophy of sake yeast Kyokai no. 7." J Biosci Bioeng 90(6);643-7. PMID: 16232925
White01: White WH, Gunyuzlu PL, Toyn JH (2001). "Saccharomyces cerevisiae is capable of de Novo pantothenic acid biosynthesis involving a novel pathway of beta-alanine production from spermine." J Biol Chem 276(14);10794-800. PMID: 11154694
Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043
Chakrabarti10: Chakrabarti KS, Thakur KG, Gopal B, Sarma SP (2010). "X-ray crystallographic and NMR studies of pantothenate synthetase provide insights into the mechanism of homotropic inhibition by pantoate." FEBS J 277(3);697-712. PMID: 20059543
Chetnani09: Chetnani B, Das S, Kumar P, Surolia A, Vijayan M (2009). "Mycobacterium tuberculosis pantothenate kinase: possible changes in location of ligands during enzyme action." Acta Crystallogr D Biol Crystallogr 65(Pt 4);312-25. PMID: 19307712
Ciulli06: Ciulli A, Williams G, Smith AG, Blundell TL, Abell C (2006). "Probing hot spots at protein-ligand binding sites: a fragment-based approach using biophysical methods." J Med Chem 49(16);4992-5000. PMID: 16884311
Ciulli07: Ciulli A, Chirgadze DY, Smith AG, Blundell TL, Abell C (2007). "Crystal structure of Escherichia coli ketopantoate reductase in a ternary complex with NADP+ and pantoate bound: substrate recognition, conformational change, and cooperativity." J Biol Chem 282(11);8487-97. PMID: 17229734
Ciulli07a: Ciulli A, Lobley CM, Tuck KL, Smith AG, Blundell TL, Abell C (2007). "pH-tuneable binding of 2'-phospho-ADP-ribose to ketopantoate reductase: a structural and calorimetric study." Acta Crystallogr D Biol Crystallogr 63(Pt 2);171-8. PMID: 17242510
Cronan82: Cronan JE, Littel KJ, Jackowski S (1982). "Genetic and biochemical analyses of pantothenate biosynthesis in Escherichia coli and Salmonella typhimurium." J Bacteriol 149(3);916-22. PMID: 7037743
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
Elischewski99: Elischewski F, Puhler A, Kalinowski J (1999). "Pantothenate production in Escherichia coli K12 by enhanced expression of the panE gene encoding ketopantoate reductase." J Biotechnol 75(2-3);135-46. PMID: 10553653
Frodyma98: Frodyma ME, Downs D (1998). "The panE gene, encoding ketopantoate reductase, maps at 10 minutes and is allelic to apbA in Salmonella typhimurium." J Bacteriol 1998;180(17);4757-9. PMID: 9721324
Genschel99: Genschel U, Powell CA, Abell C, Smith AG (1999). "The final step of pantothenate biosynthesis in higher plants: cloning and characterization of pantothenate synthetase from Lotus japonicus and Oryza sativum (rice)." Biochem J 341 ( Pt 3);669-78. PMID: 10417331
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
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