aerobactin biosynthetic process
GO:0019270
Complete four-transformation aerobactin biosynthesis in Klebsiella pneumoniae hvKP1: IucD hydroxylates lysine, IucB acetylates hydroxylysine, and IucA and IucC successively attach two building-block equivalents to citrate. The 2018 reconstruction uses hvKP1-derived enzyme preparations expressed in E. coli; the host does not establish endogenous E. coli pathway scope. The four native hvKP1 GenPept identities are retained, including IucA’s historical hypothetical-protein label and its experimentally identified 574-residue accession. The primary papers establish the source genes and describe recombinant preparations; the full sequences of all engineered constructs were not independently recovered, so exact native-to-tagged or fusion-protein sequence equality is not asserted. Gene-product enables relations preserve activity without asserting monomer sufficiency: IucA is experimentally tetrameric, whereas IucC shows ATP-associated dimer/tetramer variation. IucD and IucB preparation behavior does not establish a fixed hvKP1 stoichiometry. CHEBI:63796 is the issued lysine-S class with unspecified citrate-derived stereocenter. The hvKP1 experiments select its 3S,2′S member; this graph does not assert acceptance of the 3R member or an exact stereochemical identity between the class and that measured product. Both ligations use the native/Rhea ATP-to-AMP-plus-diphosphate convention, supported by the primary adenylation mechanism; the conflicting IUBMB IucA ATP-to-ADP equation is recorded as a source disagreement. The E. coli plasmid MetaCyc annotations ground the shared chemical pathway definition, not hvKP1 protein equivalence. Transport, iron loading, generic virulence effects, upstream precursor biosynthesis and unsupported localization or regulation are outside this complete biosynthetic boundary.
- Pathway type
- aerobactin biosynthesis
- Organism scope
Pathway network
28 nodes · 43 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
- Taxon
- Pathway
- Solid arrow: mechanistic relation
- Dashed arrow: membership, location or cofactor relation
Components and activities
| Node | Kind or role | Source direction |
|---|---|---|
Klebsiella pneumoniae hvKP1NCBITaxon:1267897 | taxon | |
waterCHEBI:15377 | small molecule | |
hydronCHEBI:15378 | small molecule | |
dioxygenCHEBI:15379 | small molecule | |
citrate(3-)CHEBI:16947 | small molecule | |
magnesium(2+)CHEBI:18420 | cofactor | |
ATP(4-)CHEBI:30616 | small molecule | |
L-lysinium(1+)CHEBI:32551 | small molecule | |
diphosphate(3-)CHEBI:33019 | small molecule | |
adenosine 5'-monophosphate(2-)CHEBI:456215 | small molecule | |
coenzyme A(4-)CHEBI:57287 | small molecule | |
acetyl-CoA(4-)CHEBI:57288 | small molecule | |
FAD(3-)CHEBI:57692 | cofactor | |
NADPH(4-)CHEBI:57783 | small molecule | |
N(6)-hydroxy-L-lysine zwitterionCHEBI:57820 | small molecule | |
N(6)-acetyl-N(6)-hydroxy-L-lysine zwitterionCHEBI:58122 | small molecule | |
NADP(3-)CHEBI:58349 | small molecule | |
aerobactinate(3-)CHEBI:58396 | small molecule | |
N(alpha)-citryl-N(epsilon)-acetyl-N(epsilon)-hydroxylysine(3-)CHEBI:63796 | small molecule | |
hypothetical protein G057_19877 [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09144.1 | protein | |
IucB [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09145.1 | protein | |
IucC [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09146.1 | protein | |
IucD [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09147.1 | protein | |
L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 | molecular activity | left to right |
N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 | molecular activity | left to right |
N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 | molecular activity | left to right |
N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 | molecular activity | left to right |
Mechanistic edges
| Subject | Predicate and description | Object | Evidence |
|---|---|---|---|
L-lysinium(1+)CHEBI:32551 | consumes | L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 |
|
NADPH(4-)CHEBI:57783 | consumes | L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 |
|
dioxygenCHEBI:15379 | consumes | L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 |
|
L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 | produces | N(6)-hydroxy-L-lysine zwitterionCHEBI:57820 |
|
L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 | produces | NADP(3-)CHEBI:58349 |
|
L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 | produces | waterCHEBI:15377 |
|
N(6)-hydroxy-L-lysine zwitterionCHEBI:57820 | consumes | N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 |
|
acetyl-CoA(4-)CHEBI:57288 | consumes | N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 |
|
N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 | produces | N(6)-acetyl-N(6)-hydroxy-L-lysine zwitterionCHEBI:58122 |
|
N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 | produces | coenzyme A(4-)CHEBI:57287 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine zwitterionCHEBI:58122 | consumes | N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 |
|
citrate(3-)CHEBI:16947 | consumes | N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 |
|
ATP(4-)CHEBI:30616 | consumes | N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 | produces CHEBI:63796 is the issued lysine-S class with unspecified citrate-derived stereocenter. The hvKP1 experiments select its 3S,2′S member; this graph does not assert acceptance of the 3R member or an exact stereochemical identity between the class and that measured product. | N(alpha)-citryl-N(epsilon)-acetyl-N(epsilon)-hydroxylysine(3-)CHEBI:63796 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 | produces | adenosine 5'-monophosphate(2-)CHEBI:456215 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 | produces | diphosphate(3-)CHEBI:33019 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 | produces | hydronCHEBI:15378 |
|
N(alpha)-citryl-N(epsilon)-acetyl-N(epsilon)-hydroxylysine(3-)CHEBI:63796 | consumes CHEBI:63796 is the issued lysine-S class with unspecified citrate-derived stereocenter. The hvKP1 experiments select its 3S,2′S member; this graph does not assert acceptance of the 3R member or an exact stereochemical identity between the class and that measured product. | N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine zwitterionCHEBI:58122 | consumes | N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 |
|
ATP(4-)CHEBI:30616 | consumes | N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 |
|
N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 | produces | aerobactinate(3-)CHEBI:58396 |
|
N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 | produces | adenosine 5'-monophosphate(2-)CHEBI:456215 |
|
N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 | produces | diphosphate(3-)CHEBI:33019 |
|
N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 | produces | hydronCHEBI:15378 |
|
IucD [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09147.1 | enables The hvKP1 IucD preparation supplied the lysine hydroxylation step in the four-enzyme reconstruction; Figure 1 assigns NADPH, oxygen and FAD to this step. Free hydroxylysine was not detected in the IucD-only assay, so that observation is not claimed as direct product identification. | L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 |
|
IucB [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09145.1 | enables The hvKP1 IucB preparation, together with IucD, produced N6-acetyl-N6-hydroxylysine in the reconstructed pathway. The assay used a cleavable fusion preparation; the E. coli native IucB hexamer annotation is not transferred to this hvKP1 protein. | N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 |
|
hypothetical protein G057_19877 [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09144.1 | enables The hvKP1 IucA gene product enables the first citrate ligation. Direct solution measurements support a tetramer of the selected 574-residue protein. This gene-product role does not claim monomer sufficiency. Both substrate selection and stereoselectivity were tested in the complete pathway study. | N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 |
|
IucC [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09146.1 | enables The hvKP1 IucC gene product enables the second ligation. Wild-type solution studies detected tetramer and dimer populations with an ATP-associated shift toward dimer; the crystal structure used a surface mutant. This role does not assert monomer sufficiency or a fixed assembly under all conditions. | N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 |
|
L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 | part_of | GO:0019270 |
|
N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 | part_of | GO:0019270 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 | part_of | GO:0019270 |
|
N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 | part_of | GO:0019270 |
|
L-lysine + NADPH + O2 => N(6)-hydroxy-L-lysine + NADP(+) + H2ORHEA:23229 | provides_input_for The source products and substrates independently identify the shared chemical intermediate. | N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 |
|
N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 | provides_input_for The source products and substrates independently identify the shared chemical intermediate. | N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 |
|
N(6)-acetyl-N(6)-hydroxy-L-lysine + citrate + ATP => N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + AMP + diphosphate + H(+)RHEA:32164 | provides_input_for CHEBI:63796 is the issued lysine-S class with unspecified citrate-derived stereocenter. The hvKP1 experiments select its 3S,2′S member; this graph does not assert acceptance of the 3R member or an exact stereochemical identity between the class and that measured product. | N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 |
|
N(6)-hydroxy-L-lysine + acetyl-CoA => N(6)-acetyl-N(6)-hydroxy-L-lysine + CoARHEA:22389 | provides_input_for A second equivalent of the IucB-produced building block supplies IucC; the first two transformations operate twice per aerobactin molecule. | N(2)-citryl-N(6)-acetyl-N(6)-hydroxy-L-lysine + N(6)-acetyl-N(6)-hydroxy-L-lysine + ATP => aerobactin + AMP + diphosphate + H(+)RHEA:32168 |
|
hypothetical protein G057_19877 [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09144.1 | part_of | Klebsiella pneumoniae hvKP1NCBITaxon:1267897 |
|
IucB [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09145.1 | part_of | Klebsiella pneumoniae hvKP1NCBITaxon:1267897 |
|
IucC [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09146.1 | part_of | Klebsiella pneumoniae hvKP1NCBITaxon:1267897 |
|
IucD [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09147.1 | part_of | Klebsiella pneumoniae hvKP1NCBITaxon:1267897 |
|
IucD [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09147.1 | has_cofactor FAD is the enzyme cofactor, distinct from consumed NADPH. This statement retains the diagram and reconstitution scope; it does not import the E. coli soluble-construct tetramer. | FAD(3-)CHEBI:57692 |
|
hypothetical protein G057_19877 [Klebsiella pneumoniae hvKP1]NCBIProtein:EMB09144.1 | has_cofactor Supported Mg2+ association in the ATP-bound enzyme, rather than an obligatory free-metal requirement inferred only from assay MgATP. IucC metal placement in 2018 was modeled from IucA and is not a separate direct IucC cofactor assertion. | magnesium(2+)CHEBI:18420 |
|
GO:0019270 | part_of | Klebsiella pneumoniae hvKP1NCBITaxon:1267897 |
|
References
GO:0019270Gene Ontology: aerobactin biosynthetic process (source version: QuickGO original JSON retrieved 2026-10-11)MetaCyc:AEROBACTINSYN-PWYMetaCyc aerobactin biosynthesis (source version: MetaCyc 22.5; original XML retrieved 2026-10-11)MetaCyc:1.14.13.59-RXNMetaCyc native reaction 1.14.13.59-RXN (source version: MetaCyc 22.5; original XML retrieved 2026-10-11)RHEA:23229Rhea directed reaction 23229 (source version: Rhea 142, 2026-09-02; hash covers complete original gzip RDF)MetaCyc:N6-HYDROXYLYSINE-O-ACETYLTRANSFERASE-RXNMetaCyc native reaction N6-HYDROXYLYSINE-O-ACETYLTRANSFERASE-RXN (source version: MetaCyc 22.5; original XML retrieved 2026-10-11)RHEA:22389Rhea directed reaction 22389 (source version: Rhea 142, 2026-09-02; hash covers complete original gzip RDF)MetaCyc:RXN-13054MetaCyc native reaction RXN-13054 (source version: MetaCyc 22.5; original XML retrieved 2026-10-11)RHEA:32164Rhea directed reaction 32164 (source version: Rhea 142, 2026-09-02; hash covers complete original gzip RDF)MetaCyc:RXN-13056MetaCyc native reaction RXN-13056 (source version: MetaCyc 22.5; original XML retrieved 2026-10-11)RHEA:32168Rhea directed reaction 32168 (source version: Rhea 142, 2026-09-02; hash covers complete original gzip RDF)NCBIProtein:EMB09144.1hypothetical protein G057_19877 [Klebsiella pneumoniae hvKP1] (source version: NCBI GenPept original four-record batch retrieved 2026-10-11; hash covers complete batch; entries updated 2013-02-07)NCBIProtein:EMB09145.1IucB [Klebsiella pneumoniae hvKP1] (source version: NCBI GenPept original four-record batch retrieved 2026-10-11; hash covers complete batch; entries updated 2013-02-07)NCBIProtein:EMB09146.1IucC [Klebsiella pneumoniae hvKP1] (source version: NCBI GenPept original four-record batch retrieved 2026-10-11; hash covers complete batch; entries updated 2013-02-07)NCBIProtein:EMB09147.1IucD [Klebsiella pneumoniae hvKP1] (source version: NCBI GenPept original four-record batch retrieved 2026-10-11; hash covers complete batch; entries updated 2013-02-07)NCBITaxon:1267897NCBI Taxonomy: Klebsiella pneumoniae hvKP1 (source version: NCBI Taxonomy original XML retrieved 2026-10-11)PMID:29618511Structural and functional delineation of aerobactin biosynthesis in hypervirulent Klebsiella pneumoniae (source version: Original research article; retained PMC HTML retrieved 2026-10-11)PMID:27253399Structural and Functional Characterization of Aerobactin Synthetase IucA from a Hypervirulent Pathotype of Klebsiella pneumoniae (source version: Original research article; retained PMC HTML retrieved 2026-10-11)PMID:32432457The Siderophore Synthetase IucA of the Aerobactin Biosynthetic Pathway Uses an Ordered Mechanism (source version: Original research article; retained PMC HTML retrieved 2026-10-11)EC:6.3.2.38IUBMB ExplorEnz EC 6.3.2.38 (source version: Original ExplorEnz HTML retrieved 2026-10-11; entry last modified 2019)MetaCyc:CPD-14069MetaCyc N-citryl-N-acetyl-N-hydroxy-L-lysine (source version: MetaCyc 22.5; original XML retrieved 2026-10-11)CHEBI:63796ChEBI N(alpha)-citryl-N(epsilon)-acetyl-N(epsilon)-hydroxylysine(3-) (source version: ChEBI 255; hash covers the uncompressed original Semantic SQL database)
Curation history
- codex
- CREATE — Add the complete hvKP1 aerobactin biosynthetic pathway
Created the exact GO:0019270 four-transformation route from the frozen externally reviewed draft. Includes both hydroxylysine-building-block uses, IucD/IucB and both citrate ligations, 43 mechanistic edges and 75 source evidence blocks. Retains the IUBMB ATP/ADP conflict, primary-supported AMP chemistry, the experimentally selected stereoisomer within broader CHEBI:63796, exact hvKP1 native protein identities and tagged/fusion/mutant construct limits. Source bodies remain external; selected facts, hashes and original replay receipts are in research/pathway_additions/2026-10-11-next-210. Record SHA256 3e4e50965749a9fa9dfe6319fd1462cc8329c10b7f4ab5363e7b486f2f32e3d4. Prepared on reviewed PR378 tree; actual merged baseline, identifier authority integration, canonical scientific review and final repository gates remain subsequent steps.
- CREATE — Add the complete hvKP1 aerobactin biosynthetic pathway
- codex
- REVIEW — Complete independent scientific review of hvKP1 aerobactin biosynthesis
Independent reviewer /root/verify_graph_publication saved completed pass_with_limitations review 20261011T115435Z-aerobactin-independent-review with zero corrective findings. The review binds the unchanged complete record SHA256 3e4e50965749a9fa9dfe6319fd1462cc8329c10b7f4ab5363e7b486f2f32e3d4, original-source replay, exact hvKP1 identities, chemical stereochemistry and ATP-source conflict, 48 current inputs, all seven repository gates, and independent SVG/KGX evidence preservation. The test run completed with 1131 passed, 3 skipped and 3 warnings. This history reports the saved review without altering its immutable inputs. Review validation and save exited zero; base-aware review-history check, remote PR review, CI, merge and publication are separate observations. No new scientific issue was identified.
- REVIEW — Complete independent scientific review of hvKP1 aerobactin biosynthesis