aceA (PP_4116) encodes isocitrate lyase (ICL; EC 4.1.3.1), a cytosolic enzyme of the isocitrate lyase/PEP mutase superfamily that catalyzes the reversible retro-aldol cleavage of isocitrate into succinate and glyoxylate. This is the committed, first step of the glyoxylate shunt (glyoxylate bypass), a branch of the tricarboxylic acid cycle at the isocitrate node that conserves carbon skeletons by bypassing the two oxidative decarboxylation steps of the TCA cycle. Together with malate synthase (GlcB, PP_0356), which condenses the glyoxylate produced by ICL with acetyl-CoA to form malate, the shunt enables net assimilation of two-carbon and acetyl-CoA-yielding substrates into C4 intermediates that feed gluconeogenesis and biomass formation. In Pseudomonas putida KT2440 the enzyme is required for growth on substrates that are catabolized to acetyl-CoA, including many fatty acids and alkanes (e.g. octane/octanoate); glyoxylate-shunt flux is strongly carbon-source dependent and is regulated transcriptionally (e.g. by RccR/HexR-family regulators) and post-translationally.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Root-level molecular function term that is correct but uninformative for this well-characterized enzyme. Reason: aceA is isocitrate lyase (EC 4.1.3.1); the generic 'catalytic activity' term should be replaced by the specific activity, which is independently annotated here (GO:0004451 isocitrate lyase activity). Proposed replacements: isocitrate lyase activity |
| GO:0004451 isocitrate lyase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Core molecular function. aceA/PP_4116 is isocitrate lyase (EC 4.1.3.1), catalyzing cleavage of isocitrate to succinate plus glyoxylate (RHEA:13245). Reason: Strongly supported by sequence/domain assignment (ICL/PEPM, IPR006254; TIGR01346) and consistent with the literature on the P. putida KT2440 glyoxylate shunt, where aceA induction and aceA-knockout growth phenotypes are observed under acetyl-CoA-yielding carbon sources [PMID:35651318 "aceA knockout failed to grow on octane"; PMID:30200852 "isocitrate lyase cleaves isocitrate into succinate and glyoxylate"]. |
| GO:0006097 glyoxylate cycle | IEA GO_REF:0000117 | ACCEPT | Summary: Core biological process. aceA catalyzes the committed step of the glyoxylate shunt/cycle. Reason: The glyoxylate shunt in P. putida KT2440 is encoded by aceA (PP_4116, isocitrate lyase) and glcB (PP_0356, malate synthase); transposon disruption of aceA causes serious fitness defects on fatty acids and an aceA knockout cannot grow on octane, confirming the in vivo role in the glyoxylate cycle [PMID:35651318; file:PSEPK/aceA/aceA-deep-research-falcon.md]. |
| GO:0006099 tricarboxylic acid cycle | IEA GO_REF:0000104 | MODIFY | Summary: Over-propagated process term. Isocitrate lyase acts at the isocitrate branch point but is an enzyme of the glyoxylate shunt that bypasses the TCA cycle, not a TCA cycle enzyme. Reason: The glyoxylate shunt diverts isocitrate away from the oxidative decarboxylation steps of the TCA cycle; ICL does not catalyze a reaction of the canonical TCA cycle [PMID:30200852 "the glyoxylate shunt is a branch of the TCA cycle that diverts carbon away from oxidative decarboxylation"]. The biological process is better captured by glyoxylate cycle (already annotated, GO:0006097). This IEA likely arises from electronic transfer at the shared isocitrate node and should be retargeted rather than retained as TCA cycle. Proposed replacements: glyoxylate cycle |
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