L-lysine biosynthesis I
MetaCyc:DAPLYSINESYN-PWY
L-lysine biosynthesis I converts L-aspartate to L-lysine through L-aspartate 4-semialdehyde, cyclic tetrahydrodipicolinate intermediates, a succinylated diaminopimelate branch, and meso-2,6-diaminopimelate.
- Pathway type
- amino acid biosynthesis
- Organism scope
Pathway network
61 nodes · 90 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
Components and activities
| Node | Kind or role | Source direction |
|---|---|---|
Escherichia coliNCBITaxon:562 | taxon | |
aspartate kinaseEC:2.7.2.4 | molecular activity | |
aspartate-semialdehyde dehydrogenaseEC:1.2.1.11 | molecular activity | |
4-hydroxy-tetrahydrodipicolinate synthaseEC:4.3.3.7 | molecular activity | |
4-hydroxy-tetrahydrodipicolinate reductaseEC:1.17.1.8 | molecular activity | |
tetrahydrodipicolinate N-succinyltransferaseEC:2.3.1.117 | molecular activity | |
succinyldiaminopimelate transaminaseEC:2.6.1.17 | molecular activity | |
succinyl-diaminopimelate desuccinylaseEC:3.5.1.18 | molecular activity | |
diaminopimelate epimeraseEC:5.1.1.7 | molecular activity | |
diaminopimelate decarboxylaseEC:4.1.1.20 | molecular activity | |
L-aspartateCHEBI:29991 | small molecule | |
ATPCHEBI:30616 | small molecule | |
4-phospho-L-aspartateCHEBI:57535 | small molecule | |
ADPCHEBI:456216 | small molecule | |
NADPHCHEBI:57783 | small molecule | |
H(+)CHEBI:15378 | small molecule | |
L-aspartate 4-semialdehydeCHEBI:537519 | small molecule | |
phosphateCHEBI:43474 | small molecule | |
NADP(+)CHEBI:58349 | small molecule | |
pyruvateCHEBI:15361 | small molecule | |
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinateCHEBI:67139 | small molecule | |
H2OCHEBI:15377 | small molecule | |
NADHCHEBI:57945 | small molecule | |
(S)-2,3,4,5-tetrahydrodipicolinateCHEBI:16845 | small molecule | |
NAD(+)CHEBI:57540 | small molecule | |
succinyl-CoACHEBI:57292 | small molecule | |
(S)-2-succinylamino-6-oxoheptanedioateCHEBI:15685 | small molecule | |
CoACHEBI:57287 | small molecule | |
L-glutamateCHEBI:29985 | small molecule | |
N-succinyl-(2S,6S)-2,6-diaminopimelateCHEBI:58087 | small molecule | |
2-oxoglutarateCHEBI:16810 | small molecule | |
(2S,6S)-2,6-diaminopimelateCHEBI:57609 | small molecule | |
succinateCHEBI:30031 | small molecule | |
meso-2,6-diaminopimelateCHEBI:57791 | small molecule | |
L-lysineCHEBI:32551 | small molecule | |
CO2CHEBI:16526 | small molecule | |
Bifunctional aspartokinase/homoserine dehydrogenase 1UniProtKB:P00561 | protein | |
L-threonine zwitterionCHEBI:57926 | small molecule | |
Bifunctional aspartokinase/homoserine dehydrogenase 2UniProtKB:P00562 | protein | |
Diaminopimelate decarboxylaseUniProtKB:P00861 | protein | |
pyridoxal 5'-phosphate(2-)CHEBI:597326 | cofactor | |
4-hydroxy-tetrahydrodipicolinate reductaseUniProtKB:P04036 | protein | |
cytoplasmGO:0005737 | cellular component | |
Lysine-sensitive aspartokinase 3UniProtKB:P08660 | protein | |
Diaminopimelate epimeraseUniProtKB:P0A6K1 | protein | |
4-hydroxy-tetrahydrodipicolinate synthaseUniProtKB:P0A6L2 | protein | |
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferaseUniProtKB:P0A9D8 | protein | |
Aspartate-semialdehyde dehydrogenaseUniProtKB:P0A9Q9 | protein | |
Succinyl-diaminopimelate desuccinylaseUniProtKB:P0AED7 | protein | |
zinc(2+)CHEBI:29105 | cofactor | |
cobalt(2+)CHEBI:48828 | cofactor | |
Acetylornithine/succinyldiaminopimelate aminotransferaseUniProtKB:P18335 | protein | |
ATP-dependent aspartate kinase reactionRHEA:23777 | reaction | left to right |
NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 | reaction | right to left |
4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 | reaction | left to right |
NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 | reaction | right to left |
NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 | reaction | right to left |
tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 | reaction | left to right |
N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 | reaction | right to left |
N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 | reaction | left to right |
diaminopimelate epimerase reactionRHEA:15394 | reaction | left to right |
diaminopimelate decarboxylase reactionRHEA:15102 | reaction | left to right |
Mechanistic edges
| Subject | Predicate and description | Object | Evidence |
|---|---|---|---|
L-aspartateCHEBI:29991 | consumes | ATP-dependent aspartate kinase reactionRHEA:23777 |
|
ATPCHEBI:30616 | consumes | ATP-dependent aspartate kinase reactionRHEA:23777 |
|
ATP-dependent aspartate kinase reactionRHEA:23777 | produces | ADPCHEBI:456216 |
|
ATP-dependent aspartate kinase reactionRHEA:23777 | produces | 4-phospho-L-aspartateCHEBI:57535 |
|
H(+)CHEBI:15378 | consumes | NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 |
|
4-phospho-L-aspartateCHEBI:57535 | consumes | NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 |
|
NADPHCHEBI:57783 | consumes | NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 |
|
NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 | produces | phosphateCHEBI:43474 |
|
NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 | produces | L-aspartate 4-semialdehydeCHEBI:537519 |
|
NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 | produces | NADP(+)CHEBI:58349 |
|
pyruvateCHEBI:15361 | consumes | 4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 |
|
L-aspartate 4-semialdehydeCHEBI:537519 | consumes | 4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 |
|
4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 | produces | H2OCHEBI:15377 |
|
4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 | produces | H(+)CHEBI:15378 |
|
4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 | produces | (2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinateCHEBI:67139 |
|
H(+)CHEBI:15378 | consumes | NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 |
|
NADHCHEBI:57945 | consumes | NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 |
|
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinateCHEBI:67139 | consumes | NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 |
|
NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 | produces | H2OCHEBI:15377 |
|
NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 | produces | (S)-2,3,4,5-tetrahydrodipicolinateCHEBI:16845 |
|
NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 | produces | NAD(+)CHEBI:57540 |
|
H(+)CHEBI:15378 | consumes | NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 |
|
NADPHCHEBI:57783 | consumes | NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 |
|
(2S,4S)-4-hydroxy-2,3,4,5-tetrahydrodipicolinateCHEBI:67139 | consumes | NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 |
|
NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 | produces | H2OCHEBI:15377 |
|
NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 | produces | (S)-2,3,4,5-tetrahydrodipicolinateCHEBI:16845 |
|
NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 | produces | NADP(+)CHEBI:58349 |
|
H2OCHEBI:15377 | consumes | tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 |
|
(S)-2,3,4,5-tetrahydrodipicolinateCHEBI:16845 | consumes | tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 |
|
succinyl-CoACHEBI:57292 | consumes | tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 |
|
tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 | produces | (S)-2-succinylamino-6-oxoheptanedioateCHEBI:15685 |
|
tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 | produces | CoACHEBI:57287 |
|
(S)-2-succinylamino-6-oxoheptanedioateCHEBI:15685 | consumes | N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 |
|
L-glutamateCHEBI:29985 | consumes | N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 |
|
N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 | produces | 2-oxoglutarateCHEBI:16810 |
|
N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 | produces | N-succinyl-(2S,6S)-2,6-diaminopimelateCHEBI:58087 |
|
H2OCHEBI:15377 | consumes | N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 |
|
N-succinyl-(2S,6S)-2,6-diaminopimelateCHEBI:58087 | consumes | N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 |
|
N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 | produces | succinateCHEBI:30031 |
|
N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 | produces | (2S,6S)-2,6-diaminopimelateCHEBI:57609 |
|
(2S,6S)-2,6-diaminopimelateCHEBI:57609 | consumes | diaminopimelate epimerase reactionRHEA:15394 |
|
diaminopimelate epimerase reactionRHEA:15394 | produces | meso-2,6-diaminopimelateCHEBI:57791 |
|
H(+)CHEBI:15378 | consumes | diaminopimelate decarboxylase reactionRHEA:15102 |
|
meso-2,6-diaminopimelateCHEBI:57791 | consumes | diaminopimelate decarboxylase reactionRHEA:15102 |
|
diaminopimelate decarboxylase reactionRHEA:15102 | produces | CO2CHEBI:16526 |
|
diaminopimelate decarboxylase reactionRHEA:15102 | produces | L-lysineCHEBI:32551 |
|
aspartate kinaseEC:2.7.2.4 | catalyzes | ATP-dependent aspartate kinase reactionRHEA:23777 |
|
aspartate-semialdehyde dehydrogenaseEC:1.2.1.11 | catalyzes | NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 |
|
4-hydroxy-tetrahydrodipicolinate synthaseEC:4.3.3.7 | catalyzes | 4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 |
|
4-hydroxy-tetrahydrodipicolinate reductaseEC:1.17.1.8 | catalyzes | NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 |
|
4-hydroxy-tetrahydrodipicolinate reductaseEC:1.17.1.8 | catalyzes | NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 |
|
tetrahydrodipicolinate N-succinyltransferaseEC:2.3.1.117 | catalyzes | tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 |
|
succinyldiaminopimelate transaminaseEC:2.6.1.17 | catalyzes | N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 |
|
succinyl-diaminopimelate desuccinylaseEC:3.5.1.18 | catalyzes | N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 |
|
diaminopimelate epimeraseEC:5.1.1.7 | catalyzes | diaminopimelate epimerase reactionRHEA:15394 |
|
diaminopimelate decarboxylaseEC:4.1.1.20 | catalyzes | diaminopimelate decarboxylase reactionRHEA:15102 |
|
N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 | precedes | N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 |
|
diaminopimelate epimerase reactionRHEA:15394 | precedes | diaminopimelate decarboxylase reactionRHEA:15102 |
|
tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 | precedes | N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 |
|
N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 | precedes | diaminopimelate epimerase reactionRHEA:15394 |
|
ATP-dependent aspartate kinase reactionRHEA:23777 | precedes | NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 |
|
NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 | precedes | 4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 |
|
4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 | precedes | NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 |
|
4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 | precedes | NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 |
|
NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 | precedes | tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 |
|
NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 | precedes | tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 |
|
Bifunctional aspartokinase/homoserine dehydrogenase 1UniProtKB:P00561 | enables | ATP-dependent aspartate kinase reactionRHEA:23777 |
|
L-threonine zwitterionCHEBI:57926 | regulates | Bifunctional aspartokinase/homoserine dehydrogenase 1UniProtKB:P00561 |
|
Bifunctional aspartokinase/homoserine dehydrogenase 2UniProtKB:P00562 | enables | ATP-dependent aspartate kinase reactionRHEA:23777 |
|
Diaminopimelate decarboxylaseUniProtKB:P00861 | enables | diaminopimelate decarboxylase reactionRHEA:15102 |
|
Diaminopimelate decarboxylaseUniProtKB:P00861 | has_cofactor | pyridoxal 5'-phosphate(2-)CHEBI:597326 |
|
4-hydroxy-tetrahydrodipicolinate reductaseUniProtKB:P04036 | enables | NADH-dependent dihydrodipicolinate reductase reactionRHEA:35325 |
|
4-hydroxy-tetrahydrodipicolinate reductaseUniProtKB:P04036 | enables | NADPH-dependent dihydrodipicolinate reductase reactionRHEA:35333 |
|
4-hydroxy-tetrahydrodipicolinate reductaseUniProtKB:P04036 | located_in | cytoplasmGO:0005737 |
|
Lysine-sensitive aspartokinase 3UniProtKB:P08660 | enables | ATP-dependent aspartate kinase reactionRHEA:23777 |
|
L-lysineCHEBI:32551 | inhibits | Lysine-sensitive aspartokinase 3UniProtKB:P08660 |
|
Diaminopimelate epimeraseUniProtKB:P0A6K1 | enables | diaminopimelate epimerase reactionRHEA:15394 |
|
Diaminopimelate epimeraseUniProtKB:P0A6K1 | located_in | cytoplasmGO:0005737 |
|
4-hydroxy-tetrahydrodipicolinate synthaseUniProtKB:P0A6L2 | enables | 4-hydroxy-tetrahydrodipicolinate synthase reactionRHEA:34172 |
|
L-lysineCHEBI:32551 | inhibits | 4-hydroxy-tetrahydrodipicolinate synthaseUniProtKB:P0A6L2 |
|
4-hydroxy-tetrahydrodipicolinate synthaseUniProtKB:P0A6L2 | located_in | cytoplasmGO:0005737 |
|
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferaseUniProtKB:P0A9D8 | enables | tetrahydrodipicolinate N-succinyltransferase reactionRHEA:17326 |
|
2,3,4,5-tetrahydropyridine-2,6-dicarboxylate N-succinyltransferaseUniProtKB:P0A9D8 | located_in | cytoplasmGO:0005737 |
|
Aspartate-semialdehyde dehydrogenaseUniProtKB:P0A9Q9 | enables | NADPH-dependent aspartate-semialdehyde dehydrogenase reactionRHEA:24286 |
|
Succinyl-diaminopimelate desuccinylaseUniProtKB:P0AED7 | enables | N-succinyldiaminopimelate desuccinylase reactionRHEA:22609 |
|
Succinyl-diaminopimelate desuccinylaseUniProtKB:P0AED7 | has_cofactor | zinc(2+)CHEBI:29105 |
|
Succinyl-diaminopimelate desuccinylaseUniProtKB:P0AED7 | has_cofactor | cobalt(2+)CHEBI:48828 |
|
Acetylornithine/succinyldiaminopimelate aminotransferaseUniProtKB:P18335 | enables | N-succinyldiaminopimelate aminotransferase reactionRHEA:11962 |
|
Acetylornithine/succinyldiaminopimelate aminotransferaseUniProtKB:P18335 | located_in | cytoplasmGO:0005737 |
|
Acetylornithine/succinyldiaminopimelate aminotransferaseUniProtKB:P18335 | has_cofactor | pyridoxal 5'-phosphate(2-)CHEBI:597326 |
|
References
MetaCyc:DAPLYSINESYN-PWYMetaCyc L-lysine biosynthesis I pathway (source version: 22.5)RHEA:23776Rhea aspartate kinase reaction (source version: 139)RHEA:23777Rhea L-aspartyl-4-phosphate-forming aspartate kinase direction (source version: 139)RHEA:24284Rhea aspartate-semialdehyde dehydrogenase reaction (source version: 139)RHEA:24286Rhea biosynthetic aspartate-semialdehyde dehydrogenase direction (source version: 139)RHEA:34171Rhea 4-hydroxy-tetrahydrodipicolinate synthase reaction (source version: 139)RHEA:34172Rhea 4-hydroxy-tetrahydrodipicolinate-forming direction (source version: 139)RHEA:35323Rhea NADH-dependent dihydrodipicolinate reductase reaction (source version: 139)RHEA:35325Rhea NADH-dependent tetrahydrodipicolinate-forming direction (source version: 139)RHEA:35331Rhea NADPH-dependent dihydrodipicolinate reductase reaction (source version: 139)RHEA:35333Rhea NADPH-dependent tetrahydrodipicolinate-forming direction (source version: 139)RHEA:17325Rhea tetrahydrodipicolinate N-succinyltransferase reaction (source version: 139)RHEA:17326Rhea N-succinylamino-6-oxoheptanedioate-forming direction (source version: 139)RHEA:11960Rhea succinyldiaminopimelate transaminase reaction (source version: 139)RHEA:11962Rhea N-succinyldiaminopimelate-forming transaminase direction (source version: 139)RHEA:22608Rhea succinyl-diaminopimelate desuccinylase reaction (source version: 139)RHEA:22609Rhea L,L-diaminopimelate-forming desuccinylase direction (source version: 139)RHEA:15393Rhea diaminopimelate epimerase reaction (source version: 139)RHEA:15394Rhea meso-diaminopimelate-forming epimerase direction (source version: 139)RHEA:15101Rhea diaminopimelate decarboxylase reaction (source version: 139)RHEA:15102Rhea L-lysine-forming diaminopimelate decarboxylase direction (source version: 139)UniProtKB:P00561UniProtKB:P00561 authority record (source version: 2026_03)UniProtKB:P00562UniProtKB:P00562 authority record (source version: 2026_03)UniProtKB:P00861UniProtKB:P00861 authority record (source version: 2026_03)UniProtKB:P04036UniProtKB:P04036 authority record (source version: 2026_03)UniProtKB:P08660UniProtKB:P08660 authority record (source version: 2026_03)UniProtKB:P0A6K1UniProtKB:P0A6K1 authority record (source version: 2026_03)UniProtKB:P0A6L2UniProtKB:P0A6L2 authority record (source version: 2026_03)UniProtKB:P0A9D8UniProtKB:P0A9D8 authority record (source version: 2026_03)UniProtKB:P0A9Q9UniProtKB:P0A9Q9 authority record (source version: 2026_03)UniProtKB:P0AED7UniProtKB:P0AED7 authority record (source version: 2026_03)UniProtKB:P18335UniProtKB:P18335 authority record (source version: 2026_03)
Curation history
- 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 10 to 10; 0 directed-ID corrections; 11 protein annotations, 4 cofactor annotations and 5 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.
- EDIT — Review causal chemistry and add sourced molecular context