MetaCyc Pathway: phosphopantothenate biosynthesis I
Inferred from experimentTraceable author statement to experimental support

Enzyme View:

Pathway diagram: phosphopantothenate biosynthesis I

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: BiosynthesisCofactors, Prosthetic Groups, Electron Carriers BiosynthesisVitamins BiosynthesisPantothenate 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

Expected Taxonomic Range: Bacteria , Fungi, Viridiplantae

General Background

(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].

Superpathways: pantothenate and coenzyme A biosynthesis I, pantothenate and coenzyme A biosynthesis II (plants)

Variants: phosphopantothenate biosynthesis II, phosphopantothenate biosynthesis III

Unification Links: EcoCyc:PANTO-PWY

Created 07-Oct-2003 by Arnaud M, SRI International
Revised 05-Mar-2013 by Foerster H, Boyce Thompson Institute
Last-Curated 26-Mar-2008 by Keseler I, SRI International


Begley01: Begley TP, Kinsland C, Strauss E (2001). "The biosynthesis of coenzyme A in bacteria." Vitam Horm 61;157-71. PMID: 11153265

Jackowski90: Jackowski S, Alix JH (1990). "Cloning, sequence, and expression of the pantothenate permease (panF) gene of Escherichia coli." J Bacteriol 172(7);3842-8. PMID: 2193919

Jones94: Jones, CE Jones, JE Dancer, AG Smith, C Abell "Evidence for the pathway to pantothenate in plants." Can. J. Chem (1994) 72 : 261.

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

Raman04: Raman S.B., Rathinasabapathi B. "Pantothenate synthesis in plants." Plant Science (2004) 167 : 961-968.

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

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

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Chunduru89: Chunduru SK, Mrachko GT, Calvo KC (1989). "Mechanism of ketol acid reductoisomerase--steady-state analysis and metal ion requirement." Biochemistry 28(2);486-93. PMID: 2653423

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

Clifton70: Clifton G, Bryant SR, Skinner CG (1970). "N'-(substituted) pantothenamides, antimetabolites of pantothenic acid." Arch Biochem Biophys 137(2);523-8. PMID: 4909169

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

Downs94: Downs DM, Petersen L (1994). "apbA, a new genetic locus involved in thiamine biosynthesis in Salmonella typhimurium." J Bacteriol 176(16);4858-64. PMID: 7519593

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

Flaks66: Flaks JG, Leboy PS, Birge EA, Kurland CG (1966). "Mutations and genetics concerned with the ribosome." Cold Spring Harb Symp Quant Biol 31;623-31. PMID: 4866408

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

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

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

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."

Showing only 20 references. To show more, press the button "Show all references".

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 Thu May 5, 2016, biocyc14.