L-homoserine biosynthesis

MetaCyc:HOMOSERSYN-PWY

L-homoserine biosynthesis converts L-aspartate to L-homoserine through 4-phospho-L-aspartate and L-aspartate 4-semialdehyde.

Pathway type

amino acid biosynthesis

Organism scope

Escherichia coli NCBITaxon:562

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Pathway network

22 nodes · 28 asserted directed edges

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Reaction / activity
Chemical / cofactor
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Solid arrow: mechanistic relation
Dashed arrow: membership, location or cofactor relation

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Components and activities

Declared biological components and source reaction directions
Node	Kind or role	Source direction
Escherichia coli `NCBITaxon:562`	taxon
aspartate kinase `EC:2.7.2.4`	molecular activity
aspartate-semialdehyde dehydrogenase `EC:1.2.1.11`	molecular activity
homoserine dehydrogenase `EC:1.1.1.3`	molecular activity
L-aspartate `CHEBI:29991`	small molecule
ATP `CHEBI:30616`	small molecule
4-phospho-L-aspartate `CHEBI:57535`	small molecule
ADP `CHEBI:456216`	small molecule
NADPH `CHEBI:57783`	small molecule
H+ `CHEBI:15378`	small molecule
L-aspartate 4-semialdehyde `CHEBI:537519`	small molecule
phosphate `CHEBI:43474`	small molecule
NADP(+) `CHEBI:58349`	small molecule
L-homoserine `CHEBI:57476`	small molecule
Bifunctional aspartokinase/homoserine dehydrogenase 1 `UniProtKB:P00561`	protein
L-threonine zwitterion `CHEBI:57926`	small molecule
Bifunctional aspartokinase/homoserine dehydrogenase 2 `UniProtKB:P00562`	protein
Lysine-sensitive aspartokinase 3 `UniProtKB:P08660`	protein
L-lysinium(1+) `CHEBI:32551`	small molecule
Aspartate-semialdehyde dehydrogenase `UniProtKB:P0A9Q9`	protein
ATP-dependent aspartate kinase reaction `RHEA:23777`	reaction	left to right
NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	reaction	right to left
NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	reaction	right to left

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
L-aspartate `CHEBI:29991`	consumes	ATP-dependent aspartate kinase reaction `RHEA:23777`	RHEA:23777 Source assertion: Rhea lists CHEBI:29991 on the substrates side of RHEA:23777 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23777']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP `CHEBI:30616`	consumes	ATP-dependent aspartate kinase reaction `RHEA:23777`	RHEA:23777 Source assertion: Rhea lists CHEBI:30616 on the substrates side of RHEA:23777 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23777']/rh:substrates; rh:contains/rh:compound/rh:accession`
ATP-dependent aspartate kinase reaction `RHEA:23777`	produces	ADP `CHEBI:456216`	RHEA:23777 Source assertion: Rhea lists CHEBI:456216 on the products side of RHEA:23777 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23777']/rh:products; rh:contains/rh:compound/rh:accession`
ATP-dependent aspartate kinase reaction `RHEA:23777`	produces	4-phospho-L-aspartate `CHEBI:57535`	RHEA:23777 Source assertion: Rhea lists CHEBI:57535 on the products side of RHEA:23777 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/23777']/rh:products; rh:contains/rh:compound/rh:accession`
H+ `CHEBI:15378`	consumes	NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	RHEA:24286 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:24286 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24286']/rh:substrates; rh:contains/rh:compound/rh:accession`
4-phospho-L-aspartate `CHEBI:57535`	consumes	NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	RHEA:24286 Source assertion: Rhea lists CHEBI:57535 on the substrates side of RHEA:24286 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24286']/rh:substrates; rh:contains/rh:compound/rh:accession`
NADPH `CHEBI:57783`	consumes	NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	RHEA:24286 Source assertion: Rhea lists CHEBI:57783 on the substrates side of RHEA:24286 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24286']/rh:substrates; rh:contains/rh:compound/rh:accession`
NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	produces	phosphate `CHEBI:43474`	RHEA:24286 Source assertion: Rhea lists CHEBI:43474 on the products side of RHEA:24286 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24286']/rh:products; rh:contains/rh:compound/rh:accession`
NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	produces	L-aspartate 4-semialdehyde `CHEBI:537519`	RHEA:24286 Source assertion: Rhea lists CHEBI:537519 on the products side of RHEA:24286 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24286']/rh:products; rh:contains/rh:compound/rh:accession`
NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	produces	NADP(+) `CHEBI:58349`	RHEA:24286 Source assertion: Rhea lists CHEBI:58349 on the products side of RHEA:24286 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/24286']/rh:products; rh:contains/rh:compound/rh:accession`
H+ `CHEBI:15378`	consumes	NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	RHEA:15763 Source assertion: Rhea lists CHEBI:15378 on the substrates side of RHEA:15763 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15763']/rh:substrates; rh:contains/rh:compound/rh:accession`
L-aspartate 4-semialdehyde `CHEBI:537519`	consumes	NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	RHEA:15763 Source assertion: Rhea lists CHEBI:537519 on the substrates side of RHEA:15763 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15763']/rh:substrates; rh:contains/rh:compound/rh:accession`
NADPH `CHEBI:57783`	consumes	NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	RHEA:15763 Source assertion: Rhea lists CHEBI:57783 on the substrates side of RHEA:15763 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15763']/rh:substrates; rh:contains/rh:compound/rh:accession`
NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	produces	L-homoserine `CHEBI:57476`	RHEA:15763 Source assertion: Rhea lists CHEBI:57476 on the products side of RHEA:15763 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15763']/rh:products; rh:contains/rh:compound/rh:accession`
NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	produces	NADP(+) `CHEBI:58349`	RHEA:15763 Source assertion: Rhea lists CHEBI:58349 on the products side of RHEA:15763 in this directed reaction. Source location `rdf:Description[@rdf:about='http://rdf.rhea-db.org/15763']/rh:products; rh:contains/rh:compound/rh:accession`
aspartate kinase `EC:2.7.2.4`	catalyzes	ATP-dependent aspartate kinase reaction `RHEA:23777`	RHEA:23776 Source assertion: Rhea associates EC:2.7.2.4 with the reaction family containing RHEA:23777. Source location `rh:ec`
aspartate-semialdehyde dehydrogenase `EC:1.2.1.11`	catalyzes	NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	RHEA:24284 Source assertion: Rhea associates EC:1.2.1.11 with the reaction family containing RHEA:24286. Source location `rh:ec`
homoserine dehydrogenase `EC:1.1.1.3`	catalyzes	NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	RHEA:15761 Source assertion: Rhea associates EC:1.1.1.3 with the reaction family containing RHEA:15763. Source location `rh:ec` PMID:2241177 aspartokinase-homoserine dehydrogenase I from Escherichia coli Source location `PubMed ArticleTitle`
ATP-dependent aspartate kinase reaction `RHEA:23777`	precedes	NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	MetaCyc:HOMOSERSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:23777 before RHEA:24286 in this pathway. Shared intermediate: CHEBI:57535. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	precedes	NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	MetaCyc:HOMOSERSYN-PWY Source assertion: MetaCyc pathway ordering places RHEA:24286 before RHEA:15763 in this pathway. Shared intermediate: CHEBI:537519. Source location `Pathway/reaction-ordering and reaction-layout; Rhea-to-MetaCyc cross-references`
Bifunctional aspartokinase/homoserine dehydrogenase 1 `UniProtKB:P00561`	enables	NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	UniProtKB:P00561 Source assertion: UniProt annotates UniProtKB:P00561 with catalytic activity for the reaction family of RHEA:15763. Annotation evidence: ECO:0000250; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Bifunctional aspartokinase/homoserine dehydrogenase 1 `UniProtKB:P00561`	enables	ATP-dependent aspartate kinase reaction `RHEA:23777`	UniProtKB:P00561 Source assertion: UniProt annotates UniProtKB:P00561 with catalytic activity for the reaction family of RHEA:23777. Annotation evidence: ECO:0000250; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
L-threonine zwitterion `CHEBI:57926`	regulates	Bifunctional aspartokinase/homoserine dehydrogenase 1 `UniProtKB:P00561`	UniProtKB:P00561 Source assertion: UniProt activity-regulation annotation: The enzyme activities are regulated allosterically by L-threonine Source location `comments[commentType='ACTIVITY REGULATION'].texts`
Bifunctional aspartokinase/homoserine dehydrogenase 2 `UniProtKB:P00562`	enables	NADPH-dependent homoserine dehydrogenase reaction `RHEA:15763`	UniProtKB:P00562 Source assertion: UniProt annotates UniProtKB:P00562 with catalytic activity for the reaction family of RHEA:15763. Annotation evidence: ECO:0000250; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Bifunctional aspartokinase/homoserine dehydrogenase 2 `UniProtKB:P00562`	enables	ATP-dependent aspartate kinase reaction `RHEA:23777`	UniProtKB:P00562 Source assertion: UniProt annotates UniProtKB:P00562 with catalytic activity for the reaction family of RHEA:23777. Annotation evidence: ECO:0000250; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
Lysine-sensitive aspartokinase 3 `UniProtKB:P08660`	enables	ATP-dependent aspartate kinase reaction `RHEA:23777`	UniProtKB:P08660 Source assertion: UniProt annotates UniProtKB:P08660 with catalytic activity for the reaction family of RHEA:23777. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`
L-lysinium(1+) `CHEBI:32551`	inhibits	Lysine-sensitive aspartokinase 3 `UniProtKB:P08660`	UniProtKB:P08660 Source assertion: UniProt activity-regulation annotation: Synthesis and activity are sensitive to the allosteric inhibitor lysine, one of the end metabolites of the aspartic acid family branched pathway Source location `comments[commentType='ACTIVITY REGULATION'].texts`
Aspartate-semialdehyde dehydrogenase `UniProtKB:P0A9Q9`	enables	NADPH-dependent aspartate-semialdehyde dehydrogenase reaction `RHEA:24286`	UniProtKB:P0A9Q9 Source assertion: UniProt annotates UniProtKB:P0A9Q9 with catalytic activity for the reaction family of RHEA:24286. Annotation evidence: ECO:0000269; organism taxon: NCBITaxon:83333. Source location `comments[commentType='CATALYTIC ACTIVITY'].reaction.reactionCrossReferences`

References

MetaCyc:HOMOSERSYN-PWY MetaCyc L-homoserine biosynthesis pathway (source version: 22.5)
RHEA:23777 Rhea L-aspartate kinase direction (source version: 139)
RHEA:24286 Rhea biosynthetic aspartate-semialdehyde dehydrogenase direction (source version: 139)
RHEA:15763 Rhea biosynthetic homoserine dehydrogenase direction (source version: 139)
PMID:2241177 Angeles and Viola, Archives of Biochemistry and Biophysics, 1990
RHEA:23776 RHEA:23776 authority record (source version: 139)
RHEA:24284 RHEA:24284 authority record (source version: 139)
RHEA:15761 RHEA:15761 authority record (source version: 139)
UniProtKB:P00561 UniProtKB:P00561 authority record (source version: 2026_03)
UniProtKB:P00562 UniProtKB:P00562 authority record (source version: 2026_03)
UniProtKB:P08660 UniProtKB:P08660 authority record (source version: 2026_03)
UniProtKB:P0A9Q9 UniProtKB:P0A9Q9 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 3 to 3; 0 directed-ID corrections; 4 protein annotations, 0 cofactor annotations and 0 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. Tentative sodium/metal-cation crystal-binding annotations for P00561/P00562 were excluded from has_cofactor assertions.
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