phosphopantothenate biosynthesis I

MetaCyc:PANTO-PWY

Phosphopantothenate biosynthesis I condenses 3-methyl-2-oxobutanoate with 5,10-methylene-tetrahydrofolate to form 2-dehydropantoate, reduces it to (R)-pantoate, ligates (R)-pantoate with beta-alanine to form (R)-pantothenate, and phosphorylates (R)-pantothenate to (R)-4'-phosphopantothenate.

Pathway type

cofactor biosynthesis

Organism scope

Escherichia coli NCBITaxon:562

Read the source YAML

Pathway network

34 nodes · 42 asserted directed edges

Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.

Reaction / activity
Chemical / cofactor
Protein / complex
Other participant
Cell / process context
Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

Show at full size (scroll to explore)

Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli `NCBITaxon:562`	taxon
3-methyl-2-oxobutanoate hydroxymethyltransferase `EC:2.1.2.11`	molecular activity
2-dehydropantoate reductase `EC:1.1.1.169`	molecular activity
pantoate--beta-alanine ligase `EC:6.3.2.1`	molecular activity
pantothenate kinase `EC:2.7.1.33`	molecular activity
(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate `CHEBI:15636`	small molecule
3-methyl-2-oxobutanoate `CHEBI:11851`	small molecule
H2O `CHEBI:15377`	small molecule
2-dehydropantoate `CHEBI:11561`	small molecule
(6S)-5,6,7,8-tetrahydrofolate `CHEBI:57453`	small molecule
NADPH `CHEBI:57783`	small molecule
H(+) `CHEBI:15378`	small molecule
(R)-pantoate `CHEBI:15980`	small molecule
NADP(+) `CHEBI:58349`	small molecule
beta-alanine `CHEBI:57966`	small molecule
ATP `CHEBI:30616`	small molecule
(R)-pantothenate `CHEBI:29032`	small molecule
AMP `CHEBI:456215`	small molecule
diphosphate `CHEBI:33019`	small molecule
(R)-4'-phosphopantothenate `CHEBI:10986`	small molecule
ADP `CHEBI:456216`	small molecule
Pantothenate kinase `UniProtKB:P0A6I3`	protein
coenzyme A(4-) `CHEBI:57287`	small molecule
cytoplasm `GO:0005737`	cellular component
2-dehydropantoate 2-reductase `UniProtKB:P0A9J4`	protein
3-methyl-2-oxobutanoate hydroxymethyltransferase `UniProtKB:P31057`	protein
magnesium(2+) `CHEBI:18420`	cofactor
manganese(2+) `CHEBI:29035`	cofactor
cobalt(2+) `CHEBI:48828`	cofactor
zinc(2+) `CHEBI:29105`	cofactor
Pantothenate synthetase `UniProtKB:P31663`	protein
3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	reaction	left to right
2-dehydropantoate reductase reaction `RHEA:16235`	reaction	right to left
pantothenate synthetase reaction `RHEA:10913`	reaction	left to right
pantothenate kinase reaction `RHEA:16374`	reaction	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
3-methyl-2-oxobutanoate `CHEBI:11851`	consumes	3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	RHEA:11825 Source assertion: Rhea lists CHEBI:11851 on the substrates side of RHEA:11825 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11825']/rh:substrates; rh:contains/rh:compound/rh:accession`
H2O `CHEBI:15377`	consumes	3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	RHEA:11825 Source assertion: Rhea lists CHEBI:15377 on the substrates side of RHEA:11825 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11825']/rh:substrates; rh:contains/rh:compound/rh:accession`
(6R)-5,10-methylene-5,6,7,8-tetrahydrofolate `CHEBI:15636`	consumes	3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	RHEA:11825 Source assertion: Rhea lists CHEBI:15636 on the substrates side of RHEA:11825 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11825']/rh:substrates; rh:contains/rh:compound/rh:accession`
3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	produces	2-dehydropantoate `CHEBI:11561`	RHEA:11825 Source assertion: Rhea lists CHEBI:11561 on the products side of RHEA:11825 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11825']/rh:products; rh:contains/rh:compound/rh:accession`
3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	produces	(6S)-5,6,7,8-tetrahydrofolate `CHEBI:57453`	RHEA:11825 Source assertion: Rhea lists CHEBI:57453 on the products side of RHEA:11825 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/11825']/rh:products; rh:contains/rh:compound/rh:accession`
2-dehydropantoate `CHEBI:11561`	consumes	2-dehydropantoate reductase reaction `RHEA:16235`	RHEA:16235 Source assertion: Rhea lists CHEBI:11561 on the substrates side of RHEA:16235 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16235']/rh:substrates; rh:contains/rh:compound/rh:accession`
H(+) `CHEBI:15378`	consumes	2-dehydropantoate reductase reaction `RHEA:16235`	RHEA:16235 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:16235 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16235']/rh:substrates; rh:contains/rh:compound/rh:accession`
NADPH `CHEBI:57783`	consumes	2-dehydropantoate reductase reaction `RHEA:16235`	RHEA:16235 Source assertion: Rhea lists CHEBI:57783 on the substrates side of RHEA:16235 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16235']/rh:substrates; rh:contains/rh:compound/rh:accession`
2-dehydropantoate reductase reaction `RHEA:16235`	produces	(R)-pantoate `CHEBI:15980`	RHEA:16235 Source assertion: Rhea lists CHEBI:15980 on the products side of RHEA:16235 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16235']/rh:products; rh:contains/rh:compound/rh:accession`
2-dehydropantoate reductase reaction `RHEA:16235`	produces	NADP(+) `CHEBI:58349`	RHEA:16235 Source assertion: Rhea lists CHEBI:58349 on the products side of RHEA:16235 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16235']/rh:products; rh:contains/rh:compound/rh:accession`
(R)-pantoate `CHEBI:15980`	consumes	pantothenate synthetase reaction `RHEA:10913`	RHEA:10913 Source assertion: Rhea lists CHEBI:15980 on the substrates side of RHEA:10913 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10913']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	pantothenate synthetase reaction `RHEA:10913`	RHEA:10913 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:10913 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10913']/rh:substrates; rh:contains/rh:compound/rh:accession`
beta-alanine `CHEBI:57966`	consumes	pantothenate synthetase reaction `RHEA:10913`	RHEA:10913 Source assertion: Rhea lists CHEBI:57966 on the substrates side of RHEA:10913 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10913']/rh:substrates; rh:contains/rh:compound/rh:accession`
pantothenate synthetase reaction `RHEA:10913`	produces	H(+) `CHEBI:15378`	RHEA:10913 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:10913 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10913']/rh:products; rh:contains/rh:compound/rh:accession`
pantothenate synthetase reaction `RHEA:10913`	produces	(R)-pantothenate `CHEBI:29032`	RHEA:10913 Source assertion: Rhea lists CHEBI:29032 on the products side of RHEA:10913 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10913']/rh:products; rh:contains/rh:compound/rh:accession`
pantothenate synthetase reaction `RHEA:10913`	produces	diphosphate `CHEBI:33019`	RHEA:10913 Source assertion: Rhea lists CHEBI:33019 on the products side of RHEA:10913 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10913']/rh:products; rh:contains/rh:compound/rh:accession`
pantothenate synthetase reaction `RHEA:10913`	produces	AMP `CHEBI:456215`	RHEA:10913 Source assertion: Rhea lists CHEBI:456215 on the products side of RHEA:10913 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/10913']/rh:products; rh:contains/rh:compound/rh:accession`
(R)-pantothenate `CHEBI:29032`	consumes	pantothenate kinase reaction `RHEA:16374`	RHEA:16374 Source assertion: Rhea lists CHEBI:29032 on the substrates side of RHEA:16374 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16374']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	pantothenate kinase reaction `RHEA:16374`	RHEA:16374 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:16374 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16374']/rh:substrates; rh:contains/rh:compound/rh:accession`
pantothenate kinase reaction `RHEA:16374`	produces	(R)-4'-phosphopantothenate `CHEBI:10986`	RHEA:16374 Source assertion: Rhea lists CHEBI:10986 on the products side of RHEA:16374 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16374']/rh:products; rh:contains/rh:compound/rh:accession`
pantothenate kinase reaction `RHEA:16374`	produces	H(+) `CHEBI:15378`	RHEA:16374 Source assertion: Rhea lists CHEBI:15378 on the products side of RHEA:16374 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16374']/rh:products; rh:contains/rh:compound/rh:accession`
pantothenate kinase reaction `RHEA:16374`	produces	ADP `CHEBI:456216`	RHEA:16374 Source assertion: Rhea lists CHEBI:456216 on the products side of RHEA:16374 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/16374']/rh:products; rh:contains/rh:compound/rh:accession`
3-methyl-2-oxobutanoate hydroxymethyltransferase `EC:2.1.2.11`	catalyzes	3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	RHEA:11824 Source assertion: Rhea associates EC:2.1.2.11 with the reaction family containing RHEA:11825. Source location `rh:ec`
2-dehydropantoate reductase `EC:1.1.1.169`	catalyzes	2-dehydropantoate reductase reaction `RHEA:16235`	RHEA:16233 Source assertion: Rhea associates EC:1.1.1.169 with the reaction family containing RHEA:16235. Source location `rh:ec`
pantoate--beta-alanine ligase `EC:6.3.2.1`	catalyzes	pantothenate synthetase reaction `RHEA:10913`	RHEA:10912 Source assertion: Rhea associates EC:6.3.2.1 with the reaction family containing RHEA:10913. Source location `rh:ec`
pantothenate kinase `EC:2.7.1.33`	catalyzes	pantothenate kinase reaction `RHEA:16374`	RHEA:16373 Source assertion: Rhea associates EC:2.7.1.33 with the reaction family containing RHEA:16374. Source location `rh:ec`
pantothenate synthetase reaction `RHEA:10913`	precedes	pantothenate kinase reaction `RHEA:16374`	MetaCyc:PANTO-PWY Source assertion: MetaCyc pathway ordering places RHEA:10913 before RHEA:16374 in this pathway. Shared intermediate: CHEBI:29032. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	precedes	2-dehydropantoate reductase reaction `RHEA:16235`	MetaCyc:PANTO-PWY Source assertion: MetaCyc pathway ordering places RHEA:11825 before RHEA:16235 in this pathway. Shared intermediate: CHEBI:11561. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
2-dehydropantoate reductase reaction `RHEA:16235`	precedes	pantothenate synthetase reaction `RHEA:10913`	MetaCyc:PANTO-PWY Source assertion: MetaCyc pathway ordering places RHEA:16235 before RHEA:10913 in this pathway. Shared intermediate: CHEBI:15980. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
Pantothenate kinase `UniProtKB:P0A6I3`	enables	pantothenate kinase reaction `RHEA:16374`	UniProtKB:P0A6I3 Source assertion: UniProt annotates UniProtKB:P0A6I3 with catalytic activity for the reaction family of RHEA:16374. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
coenzyme A(4-) `CHEBI:57287`	inhibits	Pantothenate kinase `UniProtKB:P0A6I3`	UniProtKB:P0A6I3 Source assertion: UniProt activity-regulation annotation: Regulated by feedback inhibition by CoA and its thioesters Source location `comments[commentType='ACTIVITY REGULATION'].texts`
Pantothenate kinase `UniProtKB:P0A6I3`	located_in	cytoplasm `GO:0005737`	UniProtKB:P0A6I3 Source assertion: UniProt locates UniProtKB:P0A6I3 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000305. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
2-dehydropantoate 2-reductase `UniProtKB:P0A9J4`	enables	2-dehydropantoate reductase reaction `RHEA:16235`	UniProtKB:P0A9J4 Source assertion: UniProt annotates UniProtKB:P0A9J4 with catalytic activity for the reaction family of RHEA:16235. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
2-dehydropantoate 2-reductase `UniProtKB:P0A9J4`	located_in	cytoplasm `GO:0005737`	UniProtKB:P0A9J4 Source assertion: UniProt locates UniProtKB:P0A9J4 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000305. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
3-methyl-2-oxobutanoate hydroxymethyltransferase `UniProtKB:P31057`	enables	3-methyl-2-oxobutanoate hydroxymethyltransferase reaction `RHEA:11825`	UniProtKB:P31057 Source assertion: UniProt annotates UniProtKB:P31057 with catalytic activity for the reaction family of RHEA:11825. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
3-methyl-2-oxobutanoate hydroxymethyltransferase `UniProtKB:P31057`	located_in	cytoplasm `GO:0005737`	UniProtKB:P31057 Source assertion: UniProt locates UniProtKB:P31057 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000305. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`
3-methyl-2-oxobutanoate hydroxymethyltransferase `UniProtKB:P31057`	has_cofactor	magnesium(2+) `CHEBI:18420`	UniProtKB:P31057 Source assertion: UniProt lists CHEBI:18420 as a cofactor of UniProtKB:P31057 (evidence: ECO:0000269). Binds 1 Mg(2+) ion per subunit. Can also use Mn(2+), Co(2+) and Zn(2+) to a lesser extent. Source location `comments[commentType='COFACTOR'].cofactors and note`
3-methyl-2-oxobutanoate hydroxymethyltransferase `UniProtKB:P31057`	has_cofactor	manganese(2+) `CHEBI:29035`	UniProtKB:P31057 Source assertion: UniProt lists CHEBI:29035 as a cofactor of UniProtKB:P31057 (evidence: ECO:0000269). Binds 1 Mg(2+) ion per subunit. Can also use Mn(2+), Co(2+) and Zn(2+) to a lesser extent. Source location `comments[commentType='COFACTOR'].cofactors and note`
3-methyl-2-oxobutanoate hydroxymethyltransferase `UniProtKB:P31057`	has_cofactor	cobalt(2+) `CHEBI:48828`	UniProtKB:P31057 Source assertion: UniProt lists CHEBI:48828 as a cofactor of UniProtKB:P31057 (evidence: ECO:0000269). Binds 1 Mg(2+) ion per subunit. Can also use Mn(2+), Co(2+) and Zn(2+) to a lesser extent. Source location `comments[commentType='COFACTOR'].cofactors and note`
3-methyl-2-oxobutanoate hydroxymethyltransferase `UniProtKB:P31057`	has_cofactor	zinc(2+) `CHEBI:29105`	UniProtKB:P31057 Source assertion: UniProt lists CHEBI:29105 as a cofactor of UniProtKB:P31057 (evidence: ECO:0000269). Binds 1 Mg(2+) ion per subunit. Can also use Mn(2+), Co(2+) and Zn(2+) to a lesser extent. Source location `comments[commentType='COFACTOR'].cofactors and note`
Pantothenate synthetase `UniProtKB:P31663`	enables	pantothenate synthetase reaction `RHEA:10913`	UniProtKB:P31663 Source assertion: UniProt annotates UniProtKB:P31663 with catalytic activity for the reaction family of RHEA:10913. Annotation evidence: curated source annotation; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Pantothenate synthetase `UniProtKB:P31663`	located_in	cytoplasm `GO:0005737`	UniProtKB:P31663 Source assertion: UniProt locates UniProtKB:P31663 in Cytoplasm (SL-0086, mapped by UniProt to GO:0005737). Annotation evidence: ECO:0000305. Source location `comments[commentType='SUBCELLULAR LOCATION'].subcellularLocations; UniProt location vocabulary GO mapping`

References

MetaCyc:PANTO-PWY MetaCyc phosphopantothenate biosynthesis I pathway (source version: 22.5)
RHEA:11824 Rhea 3-methyl-2-oxobutanoate hydroxymethyltransferase reaction (source version: 139)
RHEA:11825 Rhea 2-dehydropantoate-forming direction (source version: 139)
RHEA:16233 Rhea 2-dehydropantoate reductase reaction (source version: 139)
RHEA:16235 Rhea pantoate-forming direction (source version: 139)
RHEA:10912 Rhea pantothenate synthetase reaction (source version: 139)
RHEA:10913 Rhea pantothenate-forming direction (source version: 139)
RHEA:16373 Rhea pantothenate kinase reaction (source version: 139)
RHEA:16374 Rhea phosphopantothenate-forming direction (source version: 139)
UniProtKB:P0A6I3 UniProtKB:P0A6I3 authority record (source version: 2026_03)
UniProtKB:P0A9J4 UniProtKB:P0A9J4 authority record (source version: 2026_03)
UniProtKB:P31057 UniProtKB:P31057 authority record (source version: 2026_03)
UniProtKB:P31663 UniProtKB:P31663 authority record (source version: 2026_03)

Curation history

2026-10-05T06:25:52Z codex
- EDIT — Review causal chemistry and add sourced molecular context
  Reviewed the entire record against MetaCyc 22.5 native pathway XML (including nested pathways), Rhea 139 explicit sides and directions, ENZYME 02-Sep-2026, PubMed records, and reviewed UniProt 2026_03 annotations within the record's taxon scope. Replaced generated structured-source quotations with source_assertion and source_locator. Typed molecular activities and participants. Reaction count 4 to 4; 0 directed-ID corrections; 4 protein annotations, 4 cofactor annotations and 4 sourced locations. All Rhea reaction substrate/product sets checked against independent Rhea authority; native pathway leaf coverage and source exceptions recorded in reports/causal_graph_review/metacyc-review.json. Full source URLs, versions and byte hashes are in metacyc-sources.json. All 50 MetaCyc records passed native schema validation; six targeted chemistry/evidence regression tests passed. Missing protein or cofactor annotations are not treated as biological absence; qualifications and exclusions are preserved in the ledger.
Read this curation session