fasn-1 (F32H2.5; formerly emb-14) encodes the sole full-length type I fatty acid synthase of Caenorhabditis elegans, a 2613-residue multifunctional enzyme orthologous to human FASN. A single polypeptide carries ketoacyl synthase, malonyl/acetyl transferase, dehydratase, enoylreductase, ketoreductase, acyl carrier protein and thioesterase domains, with all catalytic residues known from human FASN conserved, and it synthesizes long-chain saturated fatty acids, mainly palmitate, de novo from acetyl-CoA, malonyl-CoA and NADPH in the cytoplasm. Its products supply membrane phospholipids, sphingolipid precursors and stored triglyceride. fasn-1 is essential: strong loss of function causes embryonic lethality with permeable eggshells or larval arrest, and weaker alleles or knockdown disrupt molting and cuticle integrity, anchor cell invasion and epidermal osmotic/antimicrobial peptide homeostasis. Expression is driven by SBP-1/SREBP and other lipogenic regulators.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004312 fatty acid synthase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA transferring overall fatty acid synthase activity (EC 2.3.1.85) from the animal/amoebozoan type I FAS clade (PTN000196555; fly, mouse, rat, human, Dictyostelium donors) to C. elegans FASN-1. Reason: FASN-1 sits squarely inside the metazoan type I FAS clade: it is the single full-length FAS gene in the worm genome, is orthologous to human FASN, carries the full KS-MAT-DH-ER-KR-ACP-TE domain order, and our alignment shows every human FASN catalytic residue conserved. In vivo, transgenic fasn-1 raises palmitate (C16:0), the canonical FAS product. No evidence of loss or divergence of the node function. This is the core function. Supporting Evidence: PMID:21178429 fasn-1 encodes a putative fatty acid synthase, orthologous to human FASN. PMID:21178429 the rescued siblings did show significantly increased levels of C16:0 (palmitic acid), the main product of FASN-1, and its elongated form C18:0 file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md Every catalytic residue annotated on human FASN (UniProt ACT_SITE) and the ACP PMID:15340492 There is one predicted FAS gene, F32H2.5, and its shorter homolog, F32H2.6, in the C. elegans genome. file:worm/fasn-1/fasn-1-deep-research-manual.md No purified-enzyme assay of *C. elegans* FASN-1 was found. |
| GO:0004312 fatty acid synthase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapped IEA (EC 2.3.1.85) for overall fatty acid synthase activity. Reason: Consistent with the IBA row for the same term: domain architecture, conserved catalytic residues and in vivo palmitate output support overall type I FAS activity. Supporting Evidence: PMID:21178429 the rescued siblings did show significantly increased levels of C16:0 (palmitic acid), the main product of FASN-1, and its elongated form C18:0 file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md Every catalytic residue annotated on human FASN (UniProt ACT_SITE) and the ACP |
| GO:0004313 [acyl-carrier-protein] S-acetyltransferase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapped IEA (EC 2.3.1.38) for [ACP] S-acetyltransferase activity, the acetyl-loading half of the bispecific malonyl/acetyl transferase (MAT) domain. Reason: FASN-1 has an acyl transferase (MAT) domain (Pfam PF00698, SMART PKS_AT) and the human MAT catalytic serine (Ser581) aligns to Ser621 in FASN-1. In animal type I FAS the single MAT domain loads both the acetyl primer and malonyl extender units onto the ACP, so this partial activity is expected. No worm-specific biochemical assay exists; support is by homology. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt PF00698; Acyl_transf_1 file:worm/fasn-1/fasn-1-uniprot.txt SM00827; PKS_AT file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md | Ser581 | malonyl/acetyl transferase (MAT) | Ser621 | |
| GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR018201 ketoacyl synthase active site; EC 2.3.1.41) for 3-oxoacyl-[ACP] synthase (KS) activity. Reason: FASN-1 carries a KS3 ketosynthase domain with the PROSITE active-site cysteine (Cys197) and the two KS histidines (His329, His367) conserved relative to human FASN. KS catalyses the condensation step of each elongation cycle. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt Ketosynthase family 3 (KS3) file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md | Cys161 | beta-ketoacyl synthase (KS) | Cys197 | |
| GO:0004316 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapped IEA (EC 1.1.1.100) for 3-oxoacyl-[ACP] reductase (NADPH), the ketoreductase (KR) step. Reason: FASN-1 contains the KR domain (Pfam PF08659 KR, SMART PKS_KR) in the canonical position after the ER domain, as in human FASN. KR catalytic residues were not tested in our alignment (none annotated on human FASN), but overall identity is 45% and the remainder of the catalytic set is fully conserved; no evidence of KR inactivation. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt PF08659; KR file:worm/fasn-1/fasn-1-uniprot.txt SM00822; PKS_KR |
| GO:0006633 fatty acid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for fatty acid biosynthetic process from the type I FAS/PKS clade. Reason: FASN-1 performs the condensation, reduction, dehydration and release steps of de novo long-chain fatty acid synthesis; it is the enzyme that executes this process (not merely required for it). In vivo, fasn-1 overexpression increases C16:0 and C18:0, and RNAi reduces triglyceride production. Supporting Evidence: PMID:21178429 the rescued siblings did show significantly increased levels of C16:0 (palmitic acid), the main product of FASN-1, and its elongated form C18:0 PMID:21524356 knockdown of the proteins encoded by these genes using RNA interference produced severe defects in triglyceride production |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined IEA (InterPro IPR018201; UniPathway UPA00094) for fatty acid biosynthetic process. Reason: Same claim as the IBA row; FASN-1 is the catalyst of de novo fatty acid synthesis in C. elegans. Supporting Evidence: PMID:21178429 the rescued siblings did show significantly increased levels of C16:0 (palmitic acid), the main product of FASN-1, and its elongated form C18:0 |
| GO:0016297 fatty acyl-[ACP] hydrolase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapped IEA (EC 3.1.2.14) for fatty acyl-[ACP] hydrolase activity, the chain-releasing thioesterase (TE) step. Reason: FASN-1 ends in a thioesterase domain (Pfam PF00975) and both human TE catalytic residues (Ser2308, His2481) are conserved as Ser2415 and His2591. Release of palmitate as free acid is consistent with the C16:0 product seen in vivo. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt PF00975; Thioesterase file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md | Ser2308 | thioesterase (TE) | Ser2415 | PMID:21178429 the rescued siblings did show significantly increased levels of C16:0 (palmitic acid), the main product of FASN-1, and its elongated form C18:0 |
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO IEA (IPR020843, enoylreductase domain) for oxidoreductase activity. Reason: True (FASN-1 has two NADPH-dependent reductase domains, ER and KR) but uninformative: it is entailed by the specific enoyl-[ACP] reductase (NADPH) and 3-oxoacyl-[ACP] reductase (NADPH) activities accepted in this review. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt SM00829; PKS_ER |
| GO:0016740 transferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO IEA (IPR001227, acyl transferase domain superfamily) for transferase activity. Reason: True but uninformative; entailed by the specific [ACP] S-acetyltransferase, [ACP] S-malonyltransferase and 3-oxoacyl-[ACP] synthase activities asserted in this review. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt PF00698; Acyl_transf_1 |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO IEA (IPR016039, thiolase-like fold of the KS domain) for acyltransferase activity. Reason: True but uninformative; 3-oxoacyl-[ACP] synthase (EC 2.3.1.41) and the MAT [ACP] S-acyltransferase activities accepted in this review are acyltransferase activities and entail this term. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt Ketosynthase family 3 (KS3) |
| GO:0019171 (3R)-hydroxyacyl-[acyl-carrier-protein] dehydratase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapped IEA (EC 4.2.1.59) for (3R)-hydroxyacyl-[ACP] dehydratase (DH) activity. Reason: FASN-1 contains the PKS/mFAS DH double-hotdog domain with the PROSITE-annotated proton acceptor His926 and proton donor Asp1078, matching human FASN His878/Asp1031. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt Proton acceptor; for dehydratase activity file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md | His878 | dehydratase (DH) proton acceptor | His926 | |
| GO:0031177 phosphopantetheine binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO IEA (IPR020806, PKS phosphopantetheine-binding site) for phosphopantetheine binding. Reason: Correct: the integral ACP domain carries the 4'-phosphopantetheine prosthetic group on Ser2248 (conserved with human Ser2156), which shuttles intermediates between catalytic domains. It is a cofactor/prosthetic-group feature supporting the catalytic activities rather than a function in its own right, so non-core. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt O-(pantetheine 4'-phosphoryl)serine file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md | Ser2156 | ACP O-(pantetheine 4'-phosphoryl)serine | Ser2248 | |
| GO:0032787 monocarboxylic acid metabolic process | IEA GO_REF:0000117 | TOO GENERAL | Summary: ARBA machine-learning IEA for monocarboxylic acid metabolic process. Reason: True (fatty acids are monocarboxylic acids) but uninformative: entailed by fatty acid biosynthetic process, accepted in this review from IBA and InterPro evidence. Support is from the fatty acid output data, not from the ARBA rule. Supporting Evidence: PMID:21178429 the rescued siblings did show significantly increased levels of C16:0 (palmitic acid), the main product of FASN-1, and its elongated form C18:0 |
| GO:0141148 enoyl-[acyl-carrier-protein] reductase (NADPH) activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC-mapped IEA (EC 1.3.1.39) for enoyl-[ACP] reductase (NADPH), the enoylreductase (ER) step. Reason: FASN-1 carries the MDR-family enoylreductase domain (SMART PKS_ER, CDD enoyl_red, InterPro IPR020843) in the canonical position. ER catalytic residues were not tested (none annotated on human FASN); no evidence of inactivation. Supporting Evidence: file:worm/fasn-1/fasn-1-uniprot.txt SM00829; PKS_ER file:worm/fasn-1/fasn-1-uniprot.txt cd05195; enoyl_red |
| GO:0004314 [acyl-carrier-protein] S-malonyltransferase activity | IC file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md | NEW | Summary: Proposed: malonyl-loading activity of the MAT domain. Reason: Animal type I FAS has a single bispecific MAT domain that loads both acetyl (EC 2.3.1.38, already annotated) and malonyl (EC 2.3.1.39) groups onto the ACP; malonyl loading is the more frequent reaction (once per elongation cycle). FASN-1 has the MAT domain (Pfam PF00698) with the catalytic serine conserved (Ser621 = human Ser581). This is a molecular function the protein itself performs; it fills an omission parallel to the existing S-acetyltransferase row rather than inferring participation from phenotype. Supporting Evidence: file:worm/fasn-1/fasn-1-bioinformatics/RESULTS.md | Ser581 | malonyl/acetyl transferase (MAT) | Ser621 | file:worm/fasn-1/fasn-1-uniprot.txt PF00698; Acyl_transf_1 |
| GO:0005737 cytoplasm | IDA PMID:39007804 De novo lipid synthesis and polarized prenylation drive cell... | NEW | Summary: Proposed: endogenously tagged FASN-1::mNG is cytoplasmic in the anchor cell. Reason: Direct observation of an endogenous knock-in fusion protein; consistent with the cytosolic location of animal FAS. The assay does not resolve cytosol from organelle-associated pools, so stay at cytoplasm. Supporting Evidence: PMID:39007804 POD-2 and FASN-1 are in the AC cytoplasm PMID:39007804 generated an endogenously tagged FASN-1::mNG |
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Download this section (compressed HTML)Q: Does purified C. elegans FASN-1 show the same product spectrum (mainly C16:0) as mammalian FASN, and can it use branched-chain primers (isobutyryl/isovaleryl-CoA) to initiate monomethyl branched-chain fatty acid synthesis?
Q: Is F32H2.6, the N-terminal FASN-1 paralog fragment, expressed as protein, and does it contribute to or interfere with FASN-1 function?
Q: Should a fatty acid synthase complex (homodimer) location be asserted for nematode FASN-1, given that dimerization is inferred only from orthology?
Experiment: Express and purify FASN-1 (or a tagged endogenous protein by pull-down) and assay overall NADPH-dependent fatty acid synthesis from acetyl-CoA and malonyl-CoA with product analysis by GC-MS, including branched-chain primers.
Experiment: Introduce catalytic-site point mutations (e.g. KS Cys197Ala, TE Ser2415Ala) by CRISPR and test viability and fatty-acid profiles, to separate enzymatic activity from scaffold roles.
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