FAE1 (KCS18; 3-ketoacyl-CoA synthase 18) is the seed-specialized condensing enzyme of the endoplasmic-reticulum fatty acid elongase (FAE) complex in Arabidopsis. It catalyzes the first, rate-defining step of each very-long-chain fatty acid (VLCFA) elongation cycle, condensing an acyl-CoA with malonyl-CoA to form a 3-ketoacyl-CoA and adding two carbons. As the chain-length-determining subunit of the elongase, FAE1 elongates C18 acyl-CoAs to C20 and C22 (and longer) monounsaturated and saturated VLCFAs that are deposited in seed triacylglycerols. It acts on saturated and monounsaturated C16/C18 substrates but not on polyunsaturated acyl-CoAs. Loss of FAE1 nearly abolishes seed VLCFAs (including erucic acid), making it a central control point for seed-oil composition.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000117 | ACCEPT | Summary: Correct localization, independently confirmed experimentally (see the IDA annotation below). VLCFA elongation occurs on the ER. |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Correct at the general level. FAE1 functions in fatty acid biosynthesis; the more specific VLCFA elongation roles are captured by the experimentally supported annotations below. |
| GO:0009922 fatty acid elongase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Correct core molecular function, also supported experimentally (EXP and IDA below). FAE1 is the condensing component of the fatty acid elongase. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Correct but general. FAE1 is an integral membrane protein of the ER (UniProt annotates transmembrane helices); the ER annotation is the informative localization. |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Correct but general. As a 3-ketoacyl-CoA synthase (condensing enzyme), FAE1 is an acyltransferase, but fatty acid elongase activity (GO:0009922) is the informative molecular function. |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | IEA GO_REF:0000002 | ACCEPT | Summary: Correct but general; this is the acyltransferase parent matching the KCS condensation chemistry. The specific fatty acid elongase activity annotation is retained as the core function. |
| GO:0009922 fatty acid elongase activity | EXP PMID:12135493 Engineering and mechanistic studies of the Arabidopsis FAE1 ... | ACCEPT | Summary: Core molecular function with direct experimental support. Mechanistic and engineering studies show FAE1/KCS18 is the beta-ketoacyl-CoA synthase (condensing enzyme) of the elongase, active on C16-C18 saturated and monounsaturated acyl-CoAs and elongating them to C20-C22 VLCFAs, with no activity on polyunsaturated substrates. [PMID:12135493] Supporting Evidence: PMID:12135493 Engineering and mechanistic studies of the Arabidopsis FAE1 beta-ketoacyl-CoA synthase, FAE1 KCS file:ARATH/FAE1/FAE1-deep-research-falcon.md KCS18 is a 3-ketoacyl-CoA synthase/condensing enzyme of the ER FAE complex and the chain-length-determining component |
| GO:0005783 endoplasmic reticulum | IDA PMID:36798704 Tackling functional redundancy of Arabidopsis fatty acid elo... | ACCEPT | Summary: Experimentally confirmed ER localization. Fluorescent fusions of Arabidopsis KCS proteins including KCS18 localize to the ER, consistent with VLCFA elongation occurring on the ER. [PMID:36798704] Supporting Evidence: PMID:36798704 The 21 Arabidopsis KCSs localize in the endoplasmic reticulum of tobacco cells. |
| GO:0009507 chloroplast | ISM GO_REF:0000122 | REMOVE | Summary: Spurious computational (sequence-model) prediction that contradicts the experimentally established ER/microsome localization. FAE1 is an ER-membrane VLCFA elongase component; there is no evidence it localizes to the chloroplast. Supporting Evidence: PMID:36798704 The 21 Arabidopsis KCSs localize in the endoplasmic reticulum of tobacco cells. PMID:12135493 The results presented here provide the initial analysis of the reaction mechanism for a membrane-bound condensing enzyme from any source and provide evidence for a mechanism similar to the soluble condensing enzymes. |
| GO:0000038 very long-chain fatty acid metabolic process | IMP PMID:7734965 Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (... | ACCEPT | Summary: Core biological process, supported by mutant phenotype. fae1 loss strongly depletes seed VLCFAs, demonstrating FAE1's role in VLCFA metabolism. [PMID:7734965] Supporting Evidence: PMID:7734965 The FATTY ACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the synthesis of very long chain fatty acids in the seed. |
| GO:0030497 fatty acid elongation | IMP PMID:7734965 Directed tagging of the Arabidopsis FATTY ACID ELONGATION1 (... | ACCEPT | Summary: Core biological process. FAE1 catalyzes the condensation step of fatty acid elongation; the fae1 mutant phenotype establishes its requirement for seed VLCFA elongation. [PMID:7734965] Supporting Evidence: PMID:7734965 The FATTY ACID ELONGATION1 (FAE1) gene of Arabidopsis is required for the synthesis of very long chain fatty acids in the seed. |
| GO:0009922 fatty acid elongase activity | IDA PMID:11341960 Active-site residues of a plant membrane-bound fatty acid el... | ACCEPT | Summary: Core molecular function with direct assay support. Active-site studies of the FAE1 KCS confirm its beta-ketoacyl-CoA synthase (condensing enzyme) activity. [PMID:11341960] Supporting Evidence: PMID:11341960 Active-site residues of a plant membrane-bound fatty acid elongase beta-ketoacyl-CoA synthase, FAE1 KCS |
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Download this section (compressed HTML)Q: How is FAE1/KCS18 substrate chain-length specificity (favoring C18->C20->C22 monounsaturated products) encoded structurally, and can it be re-engineered to tune seed-oil VLCFA profiles in oilseed feedstocks?
Experiment: Solve a cryo-EM or crystal structure of FAE1/KCS18 (alone and in complex with an acyl-CoA substrate analog) to identify the active-site residues controlling chain-length preference for C18->C20->C22 elongation.
Experiment: Perform structure-guided mutagenesis of the substrate-binding tunnel residues of FAE1/KCS18 and assay the variants in vitro and in transgenic Arabidopsis or Camelina seeds to quantify shifts in C20/C22 vs C24 product distributions.
Experiment: Reconstitute the seed FAE complex (KCS18 with KCR1, HCD/PAS2, and ECR) in yeast or insect microsomes to define the minimal complex composition required for processive C18->C22 elongation and to test whether other KCS isoforms can functionally substitute for KCS18.
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