lipA

UniProt ID: Q88DM5
Organism: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)
Review Status: DRAFT
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Gene Description

lipA encodes a radical-SAM lipoyl synthase that inserts sulfur atoms at the C6 and C8 positions of octanoyl groups already attached to lipoyl-domain lysine residues. This second step of endogenous protein lipoylation converts octanoylated domains into the mature protein-bound lipoyl cofactor used by lipoate-dependent enzyme complexes.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0003824 catalytic activity
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: Generic catalytic activity is true but uninformative for LipA.
Reason: The specific lipoate synthase term captures the evolved activity, making this broad catalytic parent redundant.
Supporting Evidence:
file:PSEPK/lipA/lipA-goa.tsv
GO:0003824 catalytic activity
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Cytoplasmic localization is plausible context for bacterial LipA.
Reason: UniProt places the protein in the cytoplasm, but localization is secondary to its radical-SAM lipoate synthase activity.
Supporting Evidence:
file:PSEPK/lipA/lipA-uniprot.txt
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_00206}.
GO:0009107 lipoate biosynthetic process
IEA
GO_REF:0000120 		MODIFY
Summary: LipA participates directly in endogenous lipoate biosynthesis.
Reason: LipA is the sulfur-insertion reaction in the endogenous two-step route that produces protein-bound lipoyl groups. GO:0009107 was obsoleted by GO (2026-08-22, replaced_by GO:0009249 protein lipoylation, obsoleted because term usage was inconsistent), so the annotation should move to the replacement term. GOA already carries an independent GO:0009249 row for this gene, so the replacement merges onto an existing annotation rather than asserting a new one.
Proposed replacements: protein lipoylation
Supporting Evidence:
file:PSEPK/lipA/lipA-uniprot.txt
CC -!- PATHWAY: Protein modification; protein lipoylation via endogenous
GO:0009249 protein lipoylation
IEA
GO_REF:0000104 		ACCEPT
Summary: Protein lipoylation is the immediate biological process for LipA.
Reason: The enzyme directly converts octanoylated lipoyl-domain lysines into lipoylated derivatives.
Supporting Evidence:
file:PSEPK/lipA/lipA-uniprot.txt
CC lipoyl domains of lipoate-dependent enzymes, thereby converting the
GO:0016783 sulfurtransferase activity
IEA
GO_REF:0000104 		MARK AS OVER ANNOTATED
Summary: Sulfurtransferase activity is a correct but redundant parent term.
Reason: GO:0016783 is an ancestor of the already annotated lipoate synthase activity, which captures the same sulfur-insertion chemistry with the physiological substrate context.
Supporting Evidence:
file:PSEPK/lipA/lipA-uniprot.txt
CC -!- FUNCTION: Catalyzes the radical-mediated insertion of two sulfur atoms
file:PSEPK/lipA/lipA-deep-research-openscientist.md
catalyzes the insertion of two sulfur atoms at the unactivated C6 and C8 positions of a protein-bound octanoyl chain to produce the lipoyl cofactor
GO:0016992 lipoate synthase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Lipoate synthase activity is the specific LipA catalytic function.
Reason: UniProt records the EC 2.8.1.8/Rhea reaction that converts octanoyl-lysyl protein to dihydrolipoyl-lysyl protein.
Supporting Evidence:
file:PSEPK/lipA/lipA-uniprot.txt
CC -!- FUNCTION: Catalyzes the radical-mediated insertion of two sulfur atoms
GO:0051536 iron-sulfur cluster binding
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: Iron-sulfur cluster binding is correct but less precise than the 4Fe-4S term.
Reason: The entry specifically records two 4Fe-4S clusters, so this generic iron-sulfur-cluster parent is redundant.
Supporting Evidence:
file:PSEPK/lipA/lipA-uniprot.txt
CC Note=Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated
GO:0051539 4 iron, 4 sulfur cluster binding
IEA
GO_REF:0000120 		KEEP AS NON CORE
Summary: Binding two 4Fe-4S clusters is required mechanistic context for LipA.
Reason: One cluster supports radical-SAM chemistry and the second supplies sulfur, but cluster binding is subordinate to the specific catalytic function.
Supporting Evidence:
file:PSEPK/lipA/lipA-uniprot.txt
CC Note=Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated

Core Functions

Radical-SAM lipoate synthase that sulfurates octanoylated lipoyl-domain lysines to form mature protein-bound lipoyl groups.

Molecular Function:
lipoate synthase activity
Directly Involved In:
protein lipoylation
Supporting Evidence:
  • file:PSEPK/lipA/lipA-uniprot.txt
    CC -!- FUNCTION: Catalyzes the radical-mediated insertion of two sulfur atoms

References

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Suggested Questions for Experts

Q: Should protein-bound sulfur insertion by LipA remain annotated to the broader lipoate biosynthetic process, or only to protein lipoylation?

Suggested Experiments

Experiment: Reconstitute Q88DM5 with defined Pseudomonas putida octanoylated GcvH and E2 lipoyl domains to confirm sulfur insertion and client range directly.

Experiment: Delete lipA and quantify lipoylation and activity of the major lipoate-dependent complexes, with native-gene complementation.

Deep Research

OpenScientist

(lipA-deep-research-openscientist.md)

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📚 Additional Documentation

Notes

(lipA-notes.md)

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