liuC (PA2013) encodes the 3-methylglutaconyl-CoA hydratase of the leucine/isovalerate utilization (Liu) pathway of Pseudomonas aeruginosa, a crotonase-family enzyme that interconverts trans-3-methylglutaconyl-CoA and (S)-3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). It sits between the methylcrotonyl-CoA carboxylase LiuB/LiuD, which makes 3-methylglutaconyl-CoA, and the HMG-CoA lyase LiuE, which cleaves HMG-CoA to acetyl-CoA and acetoacetate. In P. aeruginosa the acyclic terpene utilization (Atu) pathway for citronellol and geraniol enters the Liu pathway at methylcrotonyl-CoA, so the Liu enzymes, including LiuC, are needed for growth both on leucine or isovalerate and on acyclic monoterpenoids.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the enoyl-CoA hydratase/isomerase conserved-site signature to the root catalytic activity term. Reason: True but uninformative. The specific activity, methylglutaconyl-CoA hydratase (GO:0004490), is carried by this gene (IMP, IBA) and is a descendant. Proposed replacements: methylglutaconyl-CoA hydratase activity Supporting Evidence: file:PSEAE/liuC/liuC-uniprot.txt Belongs to the enoyl-CoA hydratase/isomerase family. |
| GO:0004490 methylglutaconyl-CoA hydratase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN001733227, whose sole seed is this gene's PseudoCAP IMP (PMID:16517656). The target appearing in its own WITH/FROM is expected. Reason: The activity is correct for LiuC itself, the only hydratase in the liu cluster between the carboxylase that makes 3-methylglutaconyl-CoA and the lyase that cleaves HMG-CoA. The node's propagation to the rest of the clade is doubtful (it contains AtuE, which acts on a different substrate, and B. subtilis PksH, a polyketide-pathway dehydratase acting on a carrier-protein-bound HMG group), but that does not affect the claim on this gene. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001733227 · PTN001733227 SUPPORTS SOURCE BUT NOT TARGET For the seed gene the term is right, but the 13-leaf clade (QuickGO 2026-10-28) includes AtuE (isohexenylglutaconyl-CoA hydratase), B. subtilis PksH (bacillaene synthase dehydratase), M. tuberculosis EchA7 and other crotonases whose substrates are unknown. UniProtKB:Q9I298 · liuC SOURCE WEAK OR INFERRED The seed is a mutant-based (IMP) MF inference; the abstract of PMID:16517656 does not describe a liuC mutant or hydratase assay. Supporting Evidence: PMID:16272386 The two subunits of MCase corresponded to liuB/liuD (PA2014/PA2012) PMID:19459965 These results demonstrate that the liuE gene of P. aeruginosa encodes for the HMG-CoA lyase |
| GO:0004490 methylglutaconyl-CoA hydratase activity | IMP PMID:16517656 The atu and liu clusters are involved in the catabolic pathw... | ACCEPT | Summary: PseudoCAP IMP from the mutational analysis of the atu and liu clusters. Sole seed of the GO:0004490 IBD at PTN001733227. Reason: The abstract does not describe a liuC mutant or a hydratase assay, and the full text could not be read, so the evidence behind the row is unverified; a mutant phenotype by itself would only show that the pathway needs the gene. The function is nevertheless clearly correct for LiuC by pathway logic (the carboxylase LiuB/LiuD makes 3-methylglutaconyl-CoA, the lyase LiuE needs HMG-CoA, and LiuC is the cluster's only crotonase), so I defer to the curator. Supporting Evidence: PMID:16517656 Mutagenesis of the atu and liu clusters showed that both are involved in AMTC and leucine catabolism by encoding the enzymes related to the geranyl-CoA and the 3-methylcrotonyl-CoA pathways, respectively. PMID:18625020 Mutants with insertion in any of the liu genes were unable to utilize acyclic terpenes or leucine/isovalerate |
| GO:0006552 L-leucine catabolic process | IMP PMID:16820476 Identification of genes and proteins necessary for catabolis... | ACCEPT | Summary: PseudoCAP IMP from insertion-mutant phenotypes of the liu cluster, which is essential for leucine and isovalerate utilization. Reason: LiuC catalyses the hydration of 3-methylglutaconyl-CoA, a step of leucine catabolism, and liu mutants cannot grow on leucine or isovalerate. This is the gene's core process. Supporting Evidence: PMID:16820476 Proteins encoded by two gene clusters (atuABCDEFGH and liuRABCDE) of Pseudomonas aeruginosa PAO1 were essential for acyclic terpene utilization (Atu) and for leucine and isovalerate utilization (Liu), respectively PMID:18625020 Mutants with insertion in any of the liu genes were unable to utilize acyclic terpenes or leucine/isovalerate |
| GO:0008300 isoprenoid catabolic process | IMP PMID:16517656 The atu and liu clusters are involved in the catabolic pathw... | MODIFY | Summary: PseudoCAP IMP; the atu and liu clusters are both needed for catabolism of acyclic monoterpenes of the citronellol family. Reason: Correct but general. The isoprenoids involved are acyclic C10 monoterpenoids (citronellol, geraniol), so GO:0016100 monoterpenoid catabolic process, a descendant, is the precise term. LiuC contributes because the Atu pathway feeds methylcrotonyl-CoA into the Liu pathway. Proposed replacements: monoterpenoid catabolic process Supporting Evidence: PMID:16517656 Our results suggest that the atu and liu clusters are bifunctional operons involved in both the AMTC and leucine catabolic pathways. PMID:16272386 The catabolic pathway of citronellol (Atu, acyclic terpene utilization) enters that of leucine/isovalerate (Liu, leucine and isovalerate utilization) at the level of methylcrotonyl-CoA. |
| GO:0046247 terpene catabolic process | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA from PTN001733227, whose sole seed is this gene's PseudoCAP IMP (PMID:16820476). Reason: For P. aeruginosa itself the claim is correct in substance (liu mutants cannot use acyclic terpenes) but the term is imprecise; citronellol and geraniol are monoterpenoid alcohols, not terpene hydrocarbons, so the row is corrected to GO:0016100, as for the IMP row. The propagation is unsound; the terpene role depends on an organism having an Atu pathway that feeds the leucine pathway, and is not a property of the hydratase inherited by the clade (see the GO_CENTRAL defect). Propagation Review Root cause: PROPAGATION BAD Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001733227 · PTN001733227 SUPPORTS SOURCE BUT NOT TARGET The 13 leaves (QuickGO 2026-10-28) are mostly in organisms with no acyclic terpene utilization pathway (Mycobacterium, Bacillus, Coxiella, Xanthomonas, Streptomyces, Chloroflexus, Monosiga). UniProtKB:Q9I298 · liuC SUPPORTS TRANSFER The seed is correct for PAO1 LiuC; the target's own annotation is the seed, which is expected. Proposed replacements: monoterpenoid catabolic process Supporting Evidence: PMID:16272386 The catabolic pathway of citronellol (Atu, acyclic terpene utilization) enters that of leucine/isovalerate (Liu, leucine and isovalerate utilization) at the level of methylcrotonyl-CoA. PMID:16820476 P. fluorescens, but not P. putida, could grow on acyclic terpenes (citronellol and citronellate), while both species were able to utilize leucine and isovalerate |
| GO:0046247 terpene catabolic process | IMP PMID:16820476 Identification of genes and proteins necessary for catabolis... | MODIFY | Summary: PseudoCAP IMP from insertion-mutant analysis of the atu and liu clusters. Sole seed of the GO:0046247 IBD at PTN001733227. Reason: The claim that LiuC is needed for acyclic terpene catabolism in P. aeruginosa is supported (liu mutants cannot use acyclic terpenes; the Atu pathway enters the Liu pathway at methylcrotonyl-CoA), and LiuC performs a step on that route. The substrates are monoterpenoid alcohols, not terpene hydrocarbons, so GO:0016100 monoterpenoid catabolic process is the accurate term. Proposed replacements: monoterpenoid catabolic process Supporting Evidence: PMID:18625020 Mutants with insertion in any of the liu genes were unable to utilize acyclic terpenes or leucine/isovalerate PMID:16272386 The catabolic pathway of citronellol (Atu, acyclic terpene utilization) enters that of leucine/isovalerate (Liu, leucine and isovalerate utilization) at the level of methylcrotonyl-CoA. |
Loading supporting content…
Download this section (compressed HTML)Q: The GO:0004490 IBD at PTN001733227 cannot be restricted to LiuC orthologs; the LUCA-level node has no subclade confined to them (LiuC's sister is AtuE, and the narrowest clade holding the three methylglutaconyl-CoA hydratases, PTN001733230, also holds AtuE, PksH and two Xanthomonas enzymes). Should the node instead carry a generic enoyl-CoA hydratase term, with GO:0004490 left at the leaves?
Experiment: Purify recombinant LiuC and assay hydration of 3-methylglutaconyl-CoA (and the reverse dehydration of HMG-CoA), testing isohexenylglutaconyl-CoA as an alternative substrate to define its specificity relative to AtuE.
Type: in vitro enzyme assay
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)