lipoate biosynthesis and incorporation I

MetaCyc:PWY0-501

The complete two-step endogenous LipB-LipA route in E. coli K-12 transfers an octanoyl group from ACP to a target-protein lysine, then inserts sulfur at C6 and C8. The endpoint is protein-bound dihydrolipoyl state, following the native MetaCyc boundary and current Rhea chemistry. Whole ACP, target-protein, ferredoxin and cluster-carrier states remain distinct from reactive-part ChEBI moieties. Rhea 142 formally releases Fe(III), consumes oxidized ferredoxin and uses four hydrons, whereas MetaCyc 22.5 releases Fe(II), consumes reduced ferredoxin and uses six; those net conventions are preserved as a source conflict, not resolved into a measured physiological electron balance. LipB has active monomer/trimer annotations; the native LipA dimer is retained alongside the UniProt monomer/dimer alternative. The selected proteins are K-12, while primary biochemical abstracts generally report E. coli without independently establishing every strain detail. The older PathBank donor labeled acetyl-ACP is rejected. Fatty-acid synthesis, LplA salvage, Fe-S cluster regeneration, and downstream lipoyl-cofactor turnover are outside the two-step boundary.

Pathway type

lipoate biosynthesis and incorporation

Organism scope

Escherichia coli K-12 NCBITaxon:83333

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Pathway network

23 nodes · 26 asserted directed edges

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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 K-12 `NCBITaxon:83333`	taxon
hydron `CHEBI:15378`	small molecule
5'-deoxyadenosine `CHEBI:17319`	small molecule
iron(3+) `CHEBI:29034`	small molecule
hydrosulfide `CHEBI:29919`	small molecule
tetra-mu3-sulfido-tetrairon `CHEBI:49883`	cofactor
L-methionine zwitterion `CHEBI:57844`	small molecule
S-adenosyl-L-methionine zwitterion `CHEBI:59789`	small molecule
oxidized [2Fe-2S]-[ferredoxin] `RHEA-COMP:10000`	protein
reduced [2Fe-2S]-[ferredoxin] `RHEA-COMP:10001`	protein
N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] `RHEA-COMP:10475`	protein
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] `RHEA-COMP:14568`	protein
[[Fe-S] cluster scaffold protein] `RHEA-COMP:14569`	protein
octanoyl-[ACP] `RHEA-COMP:9636`	protein
holo-[ACP] `RHEA-COMP:9685`	protein
L-lysyl-[protein] `RHEA-COMP:9752`	protein
N(6)-octanoyl-L-lysyl-[protein] `RHEA-COMP:9928`	protein
Octanoyltransferase `UniProtKB:P60720`	protein
Lipoyl synthase `UniProtKB:P60716`	protein
lipoyl synthase `MetaCyc:CPLX0-782`	complex
cytoplasm `GO:0005737`	cellular component
octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	molecular activity	left to right
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	molecular activity	left to right

Mechanistic edges

Mechanistic edges and their cited evidence
Subject	Predicate and description	Object	Evidence
octanoyl-[ACP] `RHEA-COMP:9636`	consumes	octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	RHEA:17666 Source assertion: RHEA:17666 assigns RHEA-COMP:9636 to substrates, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/17666 rh:substrates; http://rdf.rhea-db.org/17665_L rh:contains1 http://rdf.rhea-db.org/Participant_17665_compound_9636; rh:compound http://rdf.rhea-db.org/Compound_9636`
L-lysyl-[protein] `RHEA-COMP:9752`	consumes	octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	RHEA:17666 Source assertion: RHEA:17666 assigns RHEA-COMP:9752 to substrates, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/17666 rh:substrates; http://rdf.rhea-db.org/17665_L rh:contains1 http://rdf.rhea-db.org/Participant_17665_compound_9752; rh:compound http://rdf.rhea-db.org/Compound_9752`
octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	produces	N(6)-octanoyl-L-lysyl-[protein] `RHEA-COMP:9928`	RHEA:17666 Source assertion: RHEA:17666 assigns RHEA-COMP:9928 to products, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/17666 rh:products; http://rdf.rhea-db.org/17665_R rh:contains1 http://rdf.rhea-db.org/Participant_17665_compound_9928; rh:compound http://rdf.rhea-db.org/Compound_9928`
octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	produces	holo-[ACP] `RHEA-COMP:9685`	RHEA:17666 Source assertion: RHEA:17666 assigns RHEA-COMP:9685 to products, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/17666 rh:products; http://rdf.rhea-db.org/17665_R rh:contains1 http://rdf.rhea-db.org/Participant_17665_compound_9685; rh:compound http://rdf.rhea-db.org/Compound_9685`
octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	produces	hydron `CHEBI:15378`	RHEA:17666 Source assertion: RHEA:17666 assigns CHEBI:15378 to products, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/17666 rh:products; http://rdf.rhea-db.org/17665_R rh:contains1 http://rdf.rhea-db.org/Participant_17665_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] `RHEA-COMP:14568`	consumes Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	RHEA:16586 Source assertion: RHEA:16586 assigns RHEA-COMP:14568 to substrates, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:substrates; http://rdf.rhea-db.org/16585_L rh:contains1 http://rdf.rhea-db.org/Participant_16585_compound_14568; rh:compound http://rdf.rhea-db.org/Compound_14568`
N(6)-octanoyl-L-lysyl-[protein] `RHEA-COMP:9928`	consumes Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	RHEA:16586 Source assertion: RHEA:16586 assigns RHEA-COMP:9928 to substrates, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:substrates; http://rdf.rhea-db.org/16585_L rh:contains1 http://rdf.rhea-db.org/Participant_16585_compound_9928; rh:compound http://rdf.rhea-db.org/Compound_9928`
oxidized [2Fe-2S]-[ferredoxin] `RHEA-COMP:10000`	consumes Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	RHEA:16586 Source assertion: RHEA:16586 assigns RHEA-COMP:10000 to substrates, coefficient 2. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:substrates; http://rdf.rhea-db.org/16585_L rh:contains2 http://rdf.rhea-db.org/Participant_16585_compound_10000; rh:compound http://rdf.rhea-db.org/Compound_10000`
S-adenosyl-L-methionine zwitterion `CHEBI:59789`	consumes Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	RHEA:16586 Source assertion: RHEA:16586 assigns CHEBI:59789 to substrates, coefficient 2. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:substrates; http://rdf.rhea-db.org/16585_L rh:contains2 http://rdf.rhea-db.org/Participant_16585_compound_6127; rh:compound http://rdf.rhea-db.org/Compound_6127`
hydron `CHEBI:15378`	consumes Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	RHEA:16586 Source assertion: RHEA:16586 assigns CHEBI:15378 to substrates, coefficient 4. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:substrates; http://rdf.rhea-db.org/16585_L rh:contains4 http://rdf.rhea-db.org/Participant_16585_compound_3249; rh:compound http://rdf.rhea-db.org/Compound_3249`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	produces Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	[[Fe-S] cluster scaffold protein] `RHEA-COMP:14569`	RHEA:16586 Source assertion: RHEA:16586 assigns RHEA-COMP:14569 to products, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:products; http://rdf.rhea-db.org/16585_R rh:contains1 http://rdf.rhea-db.org/Participant_16585_compound_14569; rh:compound http://rdf.rhea-db.org/Compound_14569`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	produces Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] `RHEA-COMP:10475`	RHEA:16586 Source assertion: RHEA:16586 assigns RHEA-COMP:10475 to products, coefficient 1. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:products; http://rdf.rhea-db.org/16585_R rh:contains1 http://rdf.rhea-db.org/Participant_16585_compound_10475; rh:compound http://rdf.rhea-db.org/Compound_10475`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	produces Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	iron(3+) `CHEBI:29034`	RHEA:16586 Source assertion: RHEA:16586 assigns CHEBI:29034 to products, coefficient 4. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:products; http://rdf.rhea-db.org/16585_R rh:contains4 http://rdf.rhea-db.org/Participant_16585_compound_4615; rh:compound http://rdf.rhea-db.org/Compound_4615`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	produces Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	hydrosulfide `CHEBI:29919`	RHEA:16586 Source assertion: RHEA:16586 assigns CHEBI:29919 to products, coefficient 2. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:products; http://rdf.rhea-db.org/16585_R rh:contains2 http://rdf.rhea-db.org/Participant_16585_compound_3841; rh:compound http://rdf.rhea-db.org/Compound_3841`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	produces Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	5'-deoxyadenosine `CHEBI:17319`	RHEA:16586 Source assertion: RHEA:16586 assigns CHEBI:17319 to products, coefficient 2. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:products; http://rdf.rhea-db.org/16585_R rh:contains2 http://rdf.rhea-db.org/Participant_16585_compound_2028; rh:compound http://rdf.rhea-db.org/Compound_2028`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	produces Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	L-methionine zwitterion `CHEBI:57844`	RHEA:16586 Source assertion: RHEA:16586 assigns CHEBI:57844 to products, coefficient 2. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:products; http://rdf.rhea-db.org/16585_R rh:contains2 http://rdf.rhea-db.org/Participant_16585_compound_2530; rh:compound http://rdf.rhea-db.org/Compound_2530`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	produces Current Rhea net equation, including its Fe(III)/ferredoxin convention; this is not a measured physiological electron balance. MetaCyc 22.5 instead releases Fe(II), consumes reduced ferredoxin and uses six hydrons. The complete source discrepancy is retained in the curation ledger.	reduced [2Fe-2S]-[ferredoxin] `RHEA-COMP:10001`	RHEA:16586 Source assertion: RHEA:16586 assigns RHEA-COMP:10001 to products, coefficient 2. Whole carrier states are retained where the source uses a generic polypeptide. Source location `http://rdf.rhea-db.org/16586 rh:products; http://rdf.rhea-db.org/16585_R rh:contains2 http://rdf.rhea-db.org/Participant_16585_compound_10001; rh:compound http://rdf.rhea-db.org/Compound_10001`
Octanoyltransferase `UniProtKB:P60720`	catalyzes The protein node includes the experimentally annotated active monomer; a separate stable external homotrimer identity was not established. Selecting physiological transfer does not deny the measured reverse reaction.	octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	UniProtKB:P60720 Source assertion: K-12 LipB FUNCTION supports octanoyl transfer with experimental citations 15642479/16342964; the separate RHEA:17665 catalytic annotation is HAMAP ECO:0000255. SUBUNIT reports active monomer and homotrimer with ECO:0000269 PMID:15642479. Source location `/organism/taxonId; /comments/0; /comments/1; /comments/4` PMID:12591875 Source assertion: Purified E. coli LipB transfers octanoyl or lipoyl groups from ACP thioesters to a pyruvate-dehydrogenase lipoyl domain. The upstream TTG start yields functional protein; the historically assigned ATG yields an inactive truncated form. Source location `/resultList/result[id="12591875"]/abstractText` PMID:15642479 Source assertion: The primary abstract reports purified LipB transfer of octanoyl-ACP to apo-H protein, with apparent Km values for both substrates. It does not separately document the oligomer comparison in the inspected abstract. Source location `/resultList/result[id="15642479"]/abstractText` PMID:16342964 Source assertion: An isolated octanoyl-C169 LipB thioester transfers its acyl group to an E. coli PDH domain or back to ACP; the paper supports an acyl-enzyme mechanism and reversibility in vitro. Source location `/resultList/result[id="16342964"]/abstractText` RHEA:17666 Source assertion: RHEA:17665 links directional member RHEA:17666; the selected left-to-right member is the physiological octanoyl transfer. Source location `http://rdf.rhea-db.org/17665 rh:directionalReaction http://rdf.rhea-db.org/17666`
lipoyl synthase `MetaCyc:CPLX0-782`	catalyzes The catalyst is the native annotated dimer, not an assertion that only dimers can function. Current UniProt also allows monomers. The 2004 two-polypeptide mechanistic interpretation is qualified by the 2005 same-polypeptide sulfur result; neither proves every formal Rhea redox participant in vivo.	[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	MetaCyc:RXN0-949 Source assertion: RXN0-949 lists ENZRXN0-1087 with catalyst CPLX0-782 and explicitly unifies RHEA:16586. Core octanoyl-to-dihydrolipoyl chemistry agrees, while formal iron/ferredoxin/hydron conventions differ from Rhea 142. Source location `Reaction[@frameid="RXN0-949"]/enzymatic-reaction; dblink[dblink-db="RHEA"]; left; right` UniProtKB:P60716 Source assertion: Reviewed K-12 LipA supports sulfur insertion into protein-bound octanoyl groups, not free octanoate. Its catalytic activity links RHEA:16585 with HAMAP inference and experimental PMID:15157071. Source location `/organism/taxonId; /comments/0; /comments/1` PMID:14700636 Source assertion: Restoring LipA converted a deuterated octanoyl PDH domain to a lipoylated domain. Octanoyl-domain and octanoyl-PDH substrates also underwent sulfur insertion in vitro. Source location `/resultList/result[id="14700636"]/abstractText` PMID:15157071 Source assertion: Octanoylated glycine-cleavage H protein is a LipA substrate. Deuterium transfer and two SAM cleavages per formed lipoyl group support radical attack on the protein-bound chain. Source location `/resultList/result[id="15157071"]/abstractText` PMID:15740115 Source assertion: The primary experiment identifies LipA itself as the sulfur source and finds that both sulfur atoms of a lipoyl group derive from the same polypeptide. Source location `/resultList/result[id="15740115"]/abstractText`
Lipoyl synthase `UniProtKB:P60716`	part_of Two subunits in this native dimer. The record retains the source assembly without rejecting the monomer alternative.	lipoyl synthase `MetaCyc:CPLX0-782`	MetaCyc:CPLX0-782 Source assertion: CPLX0-782 contains two copies of EG11306-MONOMER. Source location `Protein[@frameid="CPLX0-782"]/component/Protein; component/coefficient` MetaCyc:EG11306-MONOMER Source assertion: EG11306-MONOMER has explicit UNIPROT P60716 unification and MG1655 native taxonomy. Source location `Protein[@frameid="EG11306-MONOMER"]/dblink[dblink-db="UNIPROT"]; species/Organism` UniProtKB:P60716 Source assertion: SUBUNIT states monomer or homodimer without an explicit evidence code; it does not establish a uniquely required oligomer. Source location `/comments/5`
Lipoyl synthase `UniProtKB:P60716`	has_cofactor CHEBI:49883 denotes the cluster class, not a fixed oxidation state. Rhea whole-carrier nodes separately retain the formal cluster states used in the reaction equation.	tetra-mu3-sulfido-tetrairon `CHEBI:49883`	UniProtKB:P60716 Source assertion: COFACTOR assigns CHEBI:49883 and two [4Fe-4S] clusters per subunit, with HAMAP ECO:0000255 and experimental ECO:0000269 PMID:15362861. Source location `/comments/2/cofactors; /comments/2/note` PMID:15362861 Source assertion: E. coli LipA accommodates two distinct [4Fe-4S] clusters per polypeptide. Mutational and spectroscopic experiments distinguish the two cysteine-binding motifs and their requirement for turnover. Source location `/resultList/result[id="15362861"]/abstractText`
Octanoyltransferase `UniProtKB:P60720`	located_in	cytoplasm `GO:0005737`	UniProtKB:P60720 Source assertion: SUBCELLULAR LOCATION annotates cytoplasm via HAMAP MF_00013, ECO:0000255; this is inferred localization, not an inspected fractionation experiment. Source location `/comments/5/subcellularLocations`
Lipoyl synthase `UniProtKB:P60716`	located_in	cytoplasm `GO:0005737`	UniProtKB:P60716 Source assertion: SUBCELLULAR LOCATION annotates cytoplasm via HAMAP MF_00206, ECO:0000255; this is inferred localization, not an inspected fractionation experiment. Source location `/comments/6/subcellularLocations`
octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	part_of	`MetaCyc:PWY0-501`	MetaCyc:PWY0-501 Source assertion: PWY0-501 explicitly lists RXN0-947 and selects its L2R layout. The pathway has exactly two reaction-list members. Source location `Pathway[@frameid="PWY0-501"]/reaction-list; reaction-layout` MetaCyc:RXN0-947 Source assertion: RXN0-947 explicitly unifies RHEA:17666. Source location `Reaction[@frameid="RXN0-947"]/dblink[dblink-db="RHEA"]`
[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	part_of	`MetaCyc:PWY0-501`	MetaCyc:PWY0-501 Source assertion: PWY0-501 explicitly lists RXN0-949 and selects its L2R layout. The pathway has exactly two reaction-list members. Source location `Pathway[@frameid="PWY0-501"]/reaction-list; reaction-layout` MetaCyc:RXN0-949 Source assertion: RXN0-949 explicitly unifies RHEA:16586. For LipA this is a route/core-chemistry bridge; versioned formal redox differences remain documented. Source location `Reaction[@frameid="RXN0-949"]/dblink[dblink-db="RHEA"]`
octanoyl-[ACP] + L-lysyl-[protein] => N(6)-octanoyl-L-lysyl-[protein] + holo-[ACP] + H(+) `RHEA:17666`	provides_input_for The route is assembly on the target protein. Neither free lipoate synthesis nor LplA-dependent salvage is appended.	[[Fe-S] cluster scaffold protein carrying a second [4Fe-4S](2+) cluster] + N(6)-octanoyl-L-lysyl-[protein] + 2 oxidized [2Fe-2S]-[ferredoxin] + 2 S-adenosyl-L-methionine + 4 H(+) => [[Fe-S] cluster scaffold protein] + N(6)-[(R)-dihydrolipoyl]-L-lysyl-[protein] + 4 Fe(3+) + 2 hydrogen sulfide + 2 5'-deoxyadenosine + 2 L-methionine + 2 reduced [2Fe-2S]-[ferredoxin] `RHEA:16586`	MetaCyc:PWY0-501 Source assertion: RXN0-949 explicitly follows RXN0-947; both layouts share Octanoylated-domains. Source location `Pathway[@frameid="PWY0-501"]/reaction-ordering; reaction-layout` RHEA:17666 Source assertion: The LipB product whole state RHEA-COMP:9928 is the identical octanoyl-protein state consumed by RHEA:16586. Source location `http://rdf.rhea-db.org/17665_R rh:contains1; http://rdf.rhea-db.org/16585_L rh:contains1; rh:compound http://rdf.rhea-db.org/Compound_9928`

References

MetaCyc:PWY0-501 lipoate biosynthesis and incorporation I (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:RXN0-947 octanoyl transfer (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:RXN0-949 lipoyl synthase reaction; native redox convention (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:CPLX0-782 lipoyl synthase native dimer (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:EG11306-MONOMER LipA native subunit (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
MetaCyc:EG11591-MONOMER LipB native protein (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)
UniProtKB:P60720 Octanoyltransferase (source version: UniProt 2026_03; full current entry retrieved 2026-10-11 UTC)
UniProtKB:P60716 Lipoyl synthase (source version: UniProt 2026_03; full current entry retrieved 2026-10-11 UTC)
PMID:12591875 The Escherichia coli lipB gene encodes lipoyl (octanoyl)-acyl carrier protein:protein transferase. (source version: 2003; primary indexed abstract inspected via Europe PMC core JSON, not full article; digest covers retained response)
PMID:14700636 Assembly of the covalent linkage between lipoic acid and its cognate enzymes. (source version: 2003; primary indexed abstract inspected via Europe PMC core JSON, not full article; digest covers retained response)
PMID:15157071 Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid. (source version: 2004; primary indexed abstract inspected via Europe PMC core JSON, not full article; digest covers retained response)
PMID:15362861 Escherichia coli lipoyl synthase binds two distinct [4Fe-4S] clusters per polypeptide. (source version: 2004; primary indexed abstract inspected via Europe PMC core JSON, not full article; digest covers retained response)
PMID:15642479 Expression, purification, and physical characterization of Escherichia coli lipoyl(octanoyl)transferase. (source version: 2005; primary indexed abstract inspected via Europe PMC core JSON, not full article; digest covers retained response)
PMID:15740115 Mechanistic investigations of lipoic acid biosynthesis in Escherichia coli: both sulfur atoms in lipoic acid are contributed by the same lipoyl synthase polypeptide. (source version: 2005; primary indexed abstract inspected via Europe PMC core JSON, not full article; digest covers retained response)
PMID:16342964 The reaction of LipB, the octanoyl-[acyl carrier protein]:protein N-octanoyltransferase of lipoic acid synthesis, proceeds through an acyl-enzyme intermediate. (source version: 2005; primary indexed abstract inspected via Europe PMC core JSON, not full article; digest covers retained response)
RHEA:17666 Rhea directional reaction 17666 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF; exact triples identified in edge locators)
RHEA:16586 Rhea directional reaction 16586 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF; exact triples identified in edge locators)

Curation history

2026-10-11T02:29:47Z Codex
- CREATE — Add the complete two-reaction LipB-LipA pathway.
  Resolved the erroneous acyl donor, retained complete protein-carrier states including both reactive parts of the cluster scaffold, preserved redox convention conflicts and native LipA dimer versus monomer alternatives, and bounded all primary assertions to inspected abstracts. Source and duplicate-search dossiers are in research/pathway_additions/2026-10-11-nicotine-next; shared authorities, generated pages, final gates and independent reviews are recorded separately.
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2026-10-11T02:32:56Z Codex
- EDIT — Place the LipA redox caveat only on LipA reaction evidence.
  Independent review found a copied LipA-only caveat on the LipB native cross-reference. Removed only that clause from lipoate-edge-024; all graph nodes, reactions and chemistry remain unchanged. Before/after source receipts and independent reassessment are retained in the cohort dossier.
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