FabB (PA1609) is the beta-ketoacyl-[acyl-carrier-protein] synthase I (KAS I, 3-oxoacyl-ACP synthase 1, EC 2.3.1.41) of Pseudomonas aeruginosa. It is a 405-residue thiolase-fold condensing enzyme with an active-site cysteine that carries the acyl group during the Claisen condensation of an acyl-ACP with malonyl-ACP, the chain-extension step of the dissociated (type II) fatty acid synthase. The gene is cotranscribed with fabA, the dehydratase/isomerase that makes the cis-3-decenoyl-ACP intermediate, and FabB is the enzyme that elongates that unsaturated intermediate - up to three further rounds - which makes it indispensable for unsaturated fatty acid synthesis; fabB mutants are auxotrophic for unsaturated fatty acids. FabB does not catalyse the final vaccenoyl-ACP step, which belongs to FabF. As the entry point into chain elongation it is a target of interest for antibacterials, and the P. aeruginosa enzyme has been crystallised as its catalytically inactive C161A variant.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the seven-seed GO:0004315 IBD at PTN000918584, the KAS I/II node, seeded by E. coli FabB (P0A953) and FabF (P0AAI5), M. tuberculosis KasA/KasB, human OXSM and two Arabidopsis KAS enzymes. PAO1 FabB is a bona fide member - crystallised, with the catalytic cysteine identified (the C161A variant) - so the inherited activity is the family-defining one and is directly supported for this protein. Reason: Sound node assertion at the right level, and the activity this protein's own structure and genetics support. Supporting Evidence: PMID:35136566 FabB is able to catalyse the elongation of cis-3-decenoyl-ACP up to three times, and synthesise cis-5-dodecenoyl-ACP, cis-7-tetradodecenoyl-ACP and cis-9-hexadodecenoyl-ACP. |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from the eight-seed GO:0006633 IBD at the same node, which this gene's own PseudoCAP row helped seed - an expected self-appearance in WITH/FROM, not circularity. FabB catalyses the condensation step of chain elongation, so it performs part of the process rather than merely being required for it. Reason: Core and directly performed. Not marked too general despite the accepted GO:0006636 descendant - FabB also elongates saturated acyl-ACPs, so the general term covers work that the unsaturated-specific term does not. Supporting Evidence: PMID:9286984 The Pseudomonas aeruginosa fabA and fabB genes, encoding beta-hydroxyacyl-acyl carrier protein dehydratase and beta-ketoacyl-acyl carrier protein synthase I, respectively, were cloned, sequenced, and expressed in Escherichia coli. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from a separate, bacteria-restricted node (PTN000196483) seeded by E. coli FabB and M. tuberculosis KasB. The dissociated type II fatty acid synthase is a soluble cytosolic system, so this is the compartment where the condensation happens. Reason: Correct for a soluble type II FAS enzyme, and the location where its activity acts. |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro signature plus the EC 2.3.1.41 mapping, agreeing with the IBA row and with the structural work on the PAO1 enzyme. Reason: Consistent electronic assertion of the demonstrated activity. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | TOO GENERAL | Summary: UniProt subcellular-location mapping. True, but GO:0005829 cytosol, accepted above, is part_of cytoplasm and is already asserted here. Reason: Entailed by the accepted cytosol row, which is the informative compartment for a soluble type II FAS enzyme. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: InterPro and UniPathway mapping of the same process claim as the IBA row. Reason: Consistent with the accepted IBA row and with the gene's genetics. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the thiolase-fold signature. True, but GO:0004315, accepted above, is a descendant of it. Reason: Uninformative given the specific 3-oxoacyl-ACP synthase activity asserted in this review. |
| GO:0006636 unsaturated fatty acid biosynthetic process | IMP PMID:9286984 Fatty acid biosynthesis in Pseudomonas aeruginosa: cloning a... | ACCEPT | Summary: PseudoCAP row and the seed of the GO:0006633 IBD at PTN000918584. The evidence is a mutant phenotype - chromosomal fabB mutants are auxotrophic for unsaturated fatty acids - but for this gene phenotype and catalysis coincide - FabB is the condensing enzyme that elongates the cis-3-decenoyl-ACP intermediate made by FabA, up to three further rounds, so losing the activity necessarily abolishes unsaturated fatty acid synthesis. This is participation, not mere necessity. Reason: Core process, performed by this enzyme's own catalytic step. The seeded node term is the parent GO:0006633, so the specific term stays on the gene without being pushed up the tree. Supporting Evidence: PMID:9286984 Chromosomal fabA and fabB mutants were isolated; the mutants were auxotrophic for unsaturated fatty acids. PMID:35136566 FabB is able to catalyse the elongation of cis-3-decenoyl-ACP up to three times, and synthesise cis-5-dodecenoyl-ACP, cis-7-tetradodecenoyl-ACP and cis-9-hexadodecenoyl-ACP. |
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Download this section (compressed HTML)Q: Has the substrate specificity of purified P. aeruginosa FabB been measured against saturated as well as unsaturated acyl-ACPs, so that the division of labour with FabF1 and FabF2 in this organism can be annotated per enzyme?
Q: Does the fabAB operon structure make FabB levels dependent on FabA regulation, and is that reflected in any condition where unsaturated fatty acid supply becomes limiting?
Experiment: Reconstitute the elongation cycle in vitro with purified PAO1 FabB, FabF1 and FabF2 and defined acyl-ACP substrates (decanoyl-ACP versus cis-3-decenoyl-ACP), measuring rates for each enzyme, with the C161A variant as a negative control.
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