PSEPK ppu00785 endogenous protein lipoylation batch

DRAFT BIOLOGY_DOMAINPIPELINE

Species: PSEPK

PSEPK ppu00785: Endogenous protein lipoylation

This batch separates cofactor installation from the many lipoate-dependent
enzymes grouped under KEGG ppu00785. The reusable module is
Endogenous protein lipoylation:
it models the conserved octanoyl-transfer and sulfur-insertion chemistry as a
direct LipB-LipA route plus separately characterized Bacillus and human
GcvH-relay variants.

The KEGG map contains 19 KT2440 genes, but only lipB and lipA catalyze these
two installation reactions. The remaining map members are lipoylated carrier
proteins or components of enzyme systems that use the installed cofactor. A
third selected locus, PP_4797, is not a KEGG member; it was promoted as a
diagnostic because its automated UniProt name says "Lipoyl synthase" even
though its 54-residue sequence is an ArfA-family ribosome-rescue protein. The
taxon-level research identified a fourth selected locus outside the KEGG
bucket, PP_0423, whose BPL/LPL-family assignment makes it an uncertain
salvage-or-GcvH-relay candidate.

Workflow Status

Pathway Satisfiability

Order Reaction KT2440 implementation Review status Decision
1 Octanoyl-ACP + apo lipoyl-domain protein to octanoylated protein lipB / PP_4801 / Q88DM4 Curated, research assessed covered
2 Octanoylated protein to lipoylated protein by sulfur insertion lipA / PP_4800 / Q88DM5 Curated, research assessed covered

Module result: covered. KT2440 has one high-confidence LipB and one
high-confidence LipA. Their adjacent genomic placement is consistent with the
two-step route, but module inclusion is grounded in the exact catalytic
functions rather than neighborhood alone.

PP_0423 / Q88QR5 is assigned to the LipM/LipL family, but the same PANTHER
subfamily contains both characterized LipM and LipL proteins. A gene-level
report proposed an LplA-type salvage hypothesis, but exact InterPro and PANTHER
classification does not distinguish the two relay-transfer directions or
establish ATP-dependent ligation. PP_0423 therefore does not yet satisfy a
relay implementation or establish salvage. The direct route remains covered
independently of this unresolved candidate.

Octanoyl-ACP production is an upstream fatty-acid-synthesis dependency. The
pyruvate, 2-oxoglutarate, branched-chain 2-oxoacid, acetoin, and glycine-cleavage
systems are downstream clients. Exogenous-lipoate salvage would require a
lipoate--protein ligase route and is outside this direct endogenous branch.

Candidate Partition

Bucket Genes Treatment
Core installation route lipB, lipA Curate here and use as exact PSEPK module exemplars
Glycine-cleavage carrier and clients gcvH1, gcvH2, gcvP1, gcvP2, gcvT-I, gcvT Lipoylated carrier proteins or client enzymes; not installation catalysts
2-oxoacid/acetoin dehydrogenase clients aceE, aceF, acoC, sucA, sucB, bkdAA, bkdAB, bkdB Cofactor-dependent complexes; not installation catalysts
Shared E3 client components lpd, lpdG, lpdV Dihydrolipoyl dehydrogenases that recycle client-bound lipoamide; not biosynthetic steps
Uncertain non-bucket BPL/LPL candidate PP_0423 Review salvage-ligase versus relay-transferase hypotheses; do not assign a specific reaction without discriminating evidence
Diagnostic nonmember PP_4797 Curate as ArfA-family ribosome rescue and exclude from lipoylation

The machine-generated 19-gene source table is retained at
ppu00785_lipoate_installation.tsv.

Selected Reviews

Gene Locus / UniProt Selection reason Current decision
lipB PP_4801 / Q88DM4 Core octanoyl-transfer step Specific MF and protein lipoylation accepted; broad acyltransferase marked over-annotated
lipA PP_4800 / Q88DM5 Core sulfur-insertion step Specific MF and lipoylation processes accepted; broad catalytic and Fe-S parents de-duplicated
PP_0423 PP_0423 / Q88QR5 BPL/LPL-family candidate found by taxon-level research Salvage-ligase versus relay-transferase role left unresolved; no GO term inferred from computational evidence alone
PP_4797 PP_4797 / Q88DM8 False lipoyl-synthase name adjacent to lipA/lipB ArfA-associated ribosome rescue accepted; excluded from module

Curation Decisions

Research

Validation

Checkpoint on 2026-07-18:

Wave 114 Repair Audit (2026-09-01)

The reusable boundary remains endogenous protein lipoylation: the direct
LipB-LipA route and the separately characterized Bacillus subtilis and human
GcvH/GCSH relay routes are modeled as topological variants. Free-lipoate
salvage, octanoyl-ACP production, and downstream lipoate-dependent client
complexes remain outside. PSEPK-specific satisfiability and the unresolved
PP_0423 candidate are documented in this batch rather than in generic variant
descriptions.

ONE_OR_MORE is retained as relaxed modeling, not as a coexistence claim. The
cited work generally presents lineage-associated alternatives; neither strict
route exclusivity nor coexistence in one genome is asserted without
organism-specific evidence.

All eight variant leaves now carry reviewed UniProt exemplars with current
names. The PSEPK LipB and LipA reviews currently carry only electronic GO
evidence, so they are not described as experimentally characterized. PANTHER
and InterPro identifiers are kept
only where labels and member containment were verified. PTN000107427 is used
for bacterial LipB activity and PTN000101947 for eukaryotic lipoyl synthase
activity because the local PAINT tables directly establish those IBD claims;
uncertain relay-family PTNs are omitted. The human LIPT1 descriptor is narrowed
from the broad PTHR12561 parent to exact PTHR12561:SF3.

The mandatory annotation-reviewer pass covered every existing GOA row for
lipA, lipB, PP_0423, and PP_4797. No gene-review YAML changes were required.
The broad GO:0016746 annotation on PSEPK lipB is already correctly marked
over-annotated beside GO:0033819. PP_0423 still has no GOA rows and no asserted
MF, while PP_4797 remains an ArfA-family ribosome-rescue protein excluded from
lipoylation.

Fresh generic OpenScientist research completed with the configured 7200-second
job allowance in 1236.73 seconds. It independently recovered the direct
LipB-LipA ordering, the Bacillus octanoyl-GcvH relay before LipA sulfur
insertion, and the human LIAS-before-LIPT1 mature-lipoyl relay. The report warns
against generalizing these lineage examples and does not establish coexistence
of the modeled routes in one organism; it also retains free-lipoate salvage and
downstream client complexes outside this module.

Wave 114 is submitted for review in pull request #2890.