FadE is the FAD-dependent acyl-CoA dehydrogenase that forms trans-2-enoyl-CoA at the entry to each fatty acid beta-oxidation turn in Escherichia coli K-12. Its physiological electron acceptor remains unresolved; a separate ETF partner has not been established. FadE is repressed by FadR and induced during fatty acid utilization. Genetic and extract assays support a range of acyl-chain substrates, but growth on shorter free fatty acids requires appropriate regulatory backgrounds and does not demonstrate complete conversion of every activated chain to acetyl-CoA.
Definition: Catalysis of oxidation of a long-chain 2,3-saturated fatty acyl-CoA to the corresponding (2E)-enoyl-CoA, transferring reducing equivalents to an electron acceptor whose molecular identity is not specified. The long-chain class follows the GO/ChEBI convention of 13 to 22 carbons; assigning this activity does not assert turnover of every member of that class.
Justification: Preserve supported substrate specificity while leaving the physiological net electron acceptor unspecified. Existing chain-specific GO dehydrogenase terms explicitly name ETF. Substrate-class activity means demonstrated capability on members of that class, not universal chain coverage. Enterobacterial genetic, extract and gene-exchange evidence is retained with its strain/regulatory context; it is not relabeled as isolated-enzyme kinetics.
Parent term: oxidoreductase activity, acting on the CH-CH group of donors
Supporting Evidence:
Definition: Catalysis of oxidation of a medium-chain 2,3-saturated fatty acyl-CoA to the corresponding (2E)-enoyl-CoA, transferring reducing equivalents to an electron acceptor whose molecular identity is not specified. The medium-chain class follows the GO/ChEBI convention of 6 to 12 carbons; assigning this activity does not assert turnover of every member of that class.
Justification: Preserve supported substrate specificity while leaving the physiological net electron acceptor unspecified. Existing chain-specific GO dehydrogenase terms explicitly name ETF. Substrate-class activity means demonstrated capability on members of that class, not universal chain coverage. Enterobacterial genetic, extract and gene-exchange evidence is retained with its strain/regulatory context; it is not relabeled as isolated-enzyme kinetics.
Parent term: oxidoreductase activity, acting on the CH-CH group of donors
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003995 acyl-CoA dehydrogenase activity | IBA GO_REF:0000033 | MODIFY | Summary: Acyl-CoA oxidation is supported, but the term explicitly assumes an unverified ETF acceptor. Reason: The active GO definition names oxidized and reduced electron-transfer flavoprotein. Primary enterobacterial genetic/physiological work establishes FadE-dependent acyl-CoA oxidation, while the physiological electron relay remains unresolved. This correction does not deny chain-length capability or demonstrate that ETF is impossible. The 2002 short-chain growth test uses a fadR background; the 1977 extract assay predates gene identification. Long- and medium-chain turnover and relative efficiency remain assay-qualified. The PAINT inference at PTN002535634 supports shared acyl-CoA oxidation; the objection concerns the term's acceptor specificity, not donor count or family membership. The structured replacement retains long and medium substrate-class capability; it does not assert activity on every chain length in those classes. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002535634 UNRESOLVED Acyl-CoA oxidation inheritance is supported; ETF specificity of the term is not established for this enterobacterial target. No inference of evolutionary loss, misplaced clade, or bad donor count is made. Proposed replacements: long-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) medium-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0003995 acyl-CoA dehydrogenase activity | IDA PMID:334745 Evidence for a complex of three beta-oxidation enzymes in Es... | MODIFY | Summary: Acyl-CoA oxidation is supported, but the term explicitly assumes an unverified ETF acceptor. Reason: The active GO definition names oxidized and reduced electron-transfer flavoprotein. Primary enterobacterial genetic/physiological work establishes FadE-dependent acyl-CoA oxidation, while the physiological electron relay remains unresolved. This correction does not deny chain-length capability or demonstrate that ETF is impossible. The 2002 short-chain growth test uses a fadR background; the 1977 extract assay predates gene identification. Long- and medium-chain turnover and relative efficiency remain assay-qualified. The structured replacement retains long and medium substrate-class capability; it does not assert activity on every chain length in those classes. Proposed replacements: long-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) medium-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0003995 acyl-CoA dehydrogenase activity | IEA GO_REF:0000002 | MODIFY | Summary: Acyl-CoA oxidation is supported, but the term explicitly assumes an unverified ETF acceptor. Reason: The active GO definition names oxidized and reduced electron-transfer flavoprotein. Primary enterobacterial genetic/physiological work establishes FadE-dependent acyl-CoA oxidation, while the physiological electron relay remains unresolved. This correction does not deny chain-length capability or demonstrate that ETF is impossible. The 2002 short-chain growth test uses a fadR background; the 1977 extract assay predates gene identification. Long- and medium-chain turnover and relative efficiency remain assay-qualified. The structured replacement retains long and medium substrate-class capability; it does not assert activity on every chain length in those classes. Proposed replacements: long-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) medium-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0003995 acyl-CoA dehydrogenase activity | IMP PMID:12057976 The enigmatic Escherichia coli fadE gene is yafH. | MODIFY | Summary: Acyl-CoA oxidation is supported, but the term explicitly assumes an unverified ETF acceptor. Reason: The active GO definition names oxidized and reduced electron-transfer flavoprotein. Primary enterobacterial genetic/physiological work establishes FadE-dependent acyl-CoA oxidation, while the physiological electron relay remains unresolved. This correction does not deny chain-length capability or demonstrate that ETF is impossible. The 2002 short-chain growth test uses a fadR background; the 1977 extract assay predates gene identification. Long- and medium-chain turnover and relative efficiency remain assay-qualified. The structured replacement retains long and medium substrate-class capability; it does not assert activity on every chain length in those classes. Proposed replacements: long-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) medium-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0004466 long-chain fatty acyl-CoA dehydrogenase activity | IEA GO_REF:0000120 | MODIFY | Summary: Acyl-CoA oxidation is supported, but the term explicitly assumes an unverified ETF acceptor. Reason: The active GO definition names oxidized and reduced electron-transfer flavoprotein. Primary enterobacterial genetic/physiological work establishes FadE-dependent acyl-CoA oxidation, while the physiological electron relay remains unresolved. This correction does not deny chain-length capability or demonstrate that ETF is impossible. The 2002 short-chain growth test uses a fadR background; the 1977 extract assay predates gene identification. Long- and medium-chain turnover and relative efficiency remain assay-qualified. The structured replacement retains long substrate-class capability; it does not assert activity on every chain length in those classes. Proposed replacements: long-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: A cytoplasmic assignment is consistent with soluble acyl-CoA-dehydrogenase activity and the enterobacterial pathway. Reason: The original fractionation study reports acyl-CoA-dehydrogenase activity in the soluble fraction, supporting the existing cellular-component assertion. It does not identify the physiological respiratory partner or rule out transient membrane interaction. Supporting Evidence: PMID:334745 acyl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase activities that utilized both C4 and C16 acyl-CoA substrates were isolated from the soluble fraction. PMID:334745 Cell fractionation was monitored, using succinic dehydrogenase as a membrane marker and glucose 6-phosphate dehydrogenase as a soluble marker. |
| GO:0005737 cytoplasm | IDA PMID:334745 Evidence for a complex of three beta-oxidation enzymes in Es... | ACCEPT | Summary: A cytoplasmic assignment is consistent with soluble acyl-CoA-dehydrogenase activity and the enterobacterial pathway. Reason: The original fractionation study reports acyl-CoA-dehydrogenase activity in the soluble fraction, supporting the existing cellular-component assertion. It does not identify the physiological respiratory partner or rule out transient membrane interaction. Supporting Evidence: PMID:334745 acyl-CoA dehydrogenase, 3-hydroxyacyl-CoA dehydrogenase, enoyl-CoA hydratase, and 3-ketoacyl-CoA thiolase activities that utilized both C4 and C16 acyl-CoA substrates were isolated from the soluble fraction. PMID:334745 Cell fractionation was monitored, using succinic dehydrogenase as a membrane marker and glucose 6-phosphate dehydrogenase as a soluble marker. |
| GO:0006635 fatty acid beta-oxidation | IEA GO_REF:0000041 | MODIFY | Summary: FadE performs the acyl-CoA-dehydrogenase entry reaction of fatty acid beta-oxidation. Reason: Refine the true broader process to GO:0033539, already present in this review. Catalytic participation is supported independently of knockout necessity; the particular downstream electron relay and completeness of substrate consumption remain unspecified. Proposed replacements: fatty acid beta-oxidation using acyl-CoA dehydrogenase Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0009062 fatty acid catabolic process | IMP PMID:4928881 Fatty acid degradation in Escherichia coli. An inducible sys... | MODIFY | Summary: FadE performs the acyl-CoA-dehydrogenase entry reaction of fatty acid beta-oxidation. Reason: Refine the true broader process to GO:0033539, already present in this review. Catalytic participation is supported independently of knockout necessity; the particular downstream electron relay and completeness of substrate consumption remain unspecified. Proposed replacements: fatty acid beta-oxidation using acyl-CoA dehydrogenase Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0016627 oxidoreductase activity, acting on the CH-CH group of donors | IEA GO_REF:0000002 | MODIFY | Summary: The CH-CH oxidoreductase claim can be refined to the established acyl-CoA reaction without specifying its acceptor. Reason: Refine the true broad oxidoreductase category to the supported acyl-CoA-to-trans-2-enoyl-CoA chemistry; the physiological acceptor is unspecified. The 2002 short-chain growth test uses a fadR background; the 1977 extract assay predates gene identification. Long- and medium-chain turnover and relative efficiency remain assay-qualified. The structured replacement retains long and medium substrate-class capability; it does not assert activity on every chain length in those classes. Proposed replacements: long-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) medium-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase | IBA GO_REF:0000033 | ACCEPT | Summary: FadE supplies the initial dehydrogenation reaction of the beta-oxidation spiral. Reason: Genetic identification, complementation and metabolite consequences support catalytic participation in this process. The process term does not establish a particular electron-accepting partner or complete oxidation of every input. The E. coli physiological efficiency remains lower than LT2 under the tested conditions. Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase | IEA GO_REF:0000002 | ACCEPT | Summary: FadE supplies the initial dehydrogenation reaction of the beta-oxidation spiral. Reason: Genetic identification, complementation and metabolite consequences support catalytic participation in this process. The process term does not establish a particular electron-accepting partner or complete oxidation of every input. The E. coli physiological efficiency remains lower than LT2 under the tested conditions. Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0033539 fatty acid beta-oxidation using acyl-CoA dehydrogenase | IMP PMID:12057976 The enigmatic Escherichia coli fadE gene is yafH. | ACCEPT | Summary: FadE supplies the initial dehydrogenation reaction of the beta-oxidation spiral. Reason: Genetic identification, complementation and metabolite consequences support catalytic participation in this process. The process term does not establish a particular electron-accepting partner or complete oxidation of every input. The E. coli physiological efficiency remains lower than LT2 under the tested conditions. Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
| GO:0050660 flavin adenine dinucleotide binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: FAD is the redox cofactor of the FadE catalytic mechanism. Reason: Retain the specific cofactor-binding claim as supporting chemistry rather than a separate core function. Homolog/domain evidence for FAD does not identify a separate ETF partner. Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Belongs to the acyl-CoA dehydrogenase family. PMID:35892328 This reaction involves the transfer of two electrons from the substrate to the FAD cofactor. |
| GO:0070991 medium-chain fatty acyl-CoA dehydrogenase activity | IEA GO_REF:0000120 | MODIFY | Summary: Acyl-CoA oxidation is supported, but the term explicitly assumes an unverified ETF acceptor. Reason: The active GO definition names oxidized and reduced electron-transfer flavoprotein. Primary enterobacterial genetic/physiological work establishes FadE-dependent acyl-CoA oxidation, while the physiological electron relay remains unresolved. This correction does not deny chain-length capability or demonstrate that ETF is impossible. The 2002 short-chain growth test uses a fadR background; the 1977 extract assay predates gene identification. Medium-chain evidence is retained in the description rather than silently discarded by the acceptor correction. The structured replacement retains medium substrate-class capability; it does not assert activity on every chain length in those classes. Proposed replacements: medium-chain fatty acyl-CoA dehydrogenase activity (acceptor unspecified) Supporting Evidence: file:ECOLI/fadE/fadE-uniprot.txt Catalyzes the dehydrogenation of acyl-coenzymes A (acyl-CoAs) to 2-enoyl-CoAs, the first step of the beta-oxidation cycle of fatty acid degradation. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md However, our array analysis and prior genetic analysis give no candidates for an ETF homologue in the FadR regulon. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md The inserts of the resultant plasmids were sequenced to verify the fidelity of the cloned PCR products. file:genes/ECOLI/fadE/fadE-source-analysis/enterobacterial-evidence.md Our results indicate that no single step of the Ξ²-oxidation cycle is responsible for the greater efficiency of the S. enterica system. |
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Download this section (compressed HTML)Q: Which respiratory partner reoxidizes FadE, and does productive turnover require transient membrane association?
Experiment: Reconstitute purified FadE with candidate respiratory acceptors and measure sustained turnover across a defined acyl-CoA chain-length panel; verify any proposed ETF interaction directly rather than presupposing a native ETF partner. Localize a functional fusion by controlled fractionation and microscopy.
Type: enzymology and subcellular fractionation
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The physiological electron acceptor and route by which reduced FadE is reoxidized are unresolved.
BIOLOGY RESIDUAL_SUBGAP
What is known: FadE-dependent acyl-CoA oxidation and fatty-acid utilization are established. This gap concerns electron transfer, not the existence of the dehydrogenation reaction.
What would resolve it: Reconstitute purified target FadE with candidate respiratory partners and directly follow electron transfer and sustained catalytic turnover.
Provenance (the field's own admissions):
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