eryCV

id: A4F7N2
gene_symbol: eryCV
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:405948
  label: Saccharopolyspora erythraea (strain ATCC 11635 / DSM 40517 / JCM 4748 / NBRC
    13426 / NCIMB 8594 / NRRL 2338)
description: >-
  EryCV is an iron-sulfur, S-adenosyl-L-methionine-dependent (radical-SAM-type) enzyme of the
  TDP-D-desosamine biosynthetic pathway in Saccharopolyspora erythraea (UniProt/EMBL/MIBiG name:
  NDP-4,6-dideoxyhexose 3,4-enoyl reductase; the DesII-type member of the cluster's deoxysugar
  enzymes). It carries a [4Fe-4S] cluster and uses SAM, consistent with a radical-SAM mechanism;
  the precise catalytic outcome on the TDP-deoxysugar intermediate is not experimentally resolved
  in the records available.
references:
- id: file:SACEN/eryCV/eryCV-uniprot.txt
  title: UniProtKB A4F7N2 (eryCV) record - "NDP-4,6-dideoxyhexose 3,4-enoyl reductase"; Fe-S + SAM
  findings:
  - statement: >-
      EryCV binds iron-sulfur and uses SAM (radical-SAM-type), acting in deoxysugar biosynthesis.
    supporting_text: >-
      EryCV NDP-4,6-dideoxyhexose 3,4-enoyl reductase
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: >-
      TrEMBL entry; iron / iron-sulfur / metal-binding / SAM keywords are consistent with a
      radical-SAM enzyme. The exact reaction (named 3,4-enoyl reductase vs the GOA ammonia-lyase
      term) is not adjudicable from the available records.
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
existing_annotations:
- term:
    id: GO:0003824
    label: catalytic activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Root-level "catalytic activity" - uninformative; EryCV is a specific iron-sulfur/SAM enzyme.
    action: MARK_AS_OVER_ANNOTATED
    reason: Generic catalytic-activity term provides no functional information; a specific MF is preferable.
- term:
    id: GO:0016841
    label: ammonia-lyase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Ammonia-lyase activity from an InterPro signature. This conflicts with the enzyme's name
      (3,4-enoyl reductase) and its radical-SAM (Fe-S/SAM) cofactor profile; DesII-type radical-SAM
      enzymes can catalyze dehydration/deamination, but the precise reaction here is unverified.
    action: UNDECIDED
    reason: >-
      Conflicting electronic assignments (ammonia-lyase vs 3,4-enoyl reductase) with no accessible
      experimental characterization; the radical-SAM cofactor binding is, however, well supported.
- term:
    id: GO:0033068
    label: macrolide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      Involvement in macrolide (erythromycin) biosynthesis via the desosamine pathway. Correct; a
      more specific child (GO:1901115) is captured in core_functions.
    action: ACCEPT
    reason: Accurate biological process.
- term:
    id: GO:0051536
    label: iron-sulfur cluster binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Iron-sulfur cluster binding; supported by the UniProt iron-sulfur keywords.
    action: ACCEPT
    reason: Correct cofactor binding for this radical-SAM-type enzyme.
    supported_by:
    - reference_id: file:SACEN/eryCV/eryCV-uniprot.txt
      supporting_text: >-
        EryCV NDP-4,6-dideoxyhexose 3,4-enoyl reductase
- term:
    id: GO:0051539
    label: 4 iron, 4 sulfur cluster binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      [4Fe-4S] cluster binding - the hallmark cofactor of a radical-SAM enzyme; supported by the
      UniProt iron/iron-sulfur/SAM keywords.
    action: ACCEPT
    reason: Correct and specific cofactor binding.
    supported_by:
    - reference_id: file:SACEN/eryCV/eryCV-uniprot.txt
      supporting_text: >-
        EryCV NDP-4,6-dideoxyhexose 3,4-enoyl reductase
core_functions:
- description: >-
    Iron-sulfur, SAM-dependent (radical-SAM-type) enzyme contributing to TDP-D-desosamine
    biosynthesis (named NDP-4,6-dideoxyhexose 3,4-enoyl reductase; DesII-type), supplying the
    aminodeoxysugar used in erythromycin biosynthesis. Binds a [4Fe-4S] cluster; the precise
    catalytic reaction awaits experimental confirmation.
  molecular_function:
    id: GO:0051539
    label: 4 iron, 4 sulfur cluster binding
  directly_involved_in:
    - id: GO:1901115
      label: erythromycin biosynthetic process
  supported_by:
  - reference_id: file:SACEN/eryCV/eryCV-uniprot.txt
    supporting_text: >-
      EryCV NDP-4,6-dideoxyhexose 3,4-enoyl reductase
suggested_questions:
- question: >-
    EVIDENCE GAP: what radical-SAM reaction does EryCV catalyze? It binds a [4Fe-4S] cluster and
    SAM (radical-SAM/DesII-type), but its UniProt/EMBL name ("3,4-enoyl reductase") and the GOA
    term ("ammonia-lyase activity") are conflicting electronic (IEA) assignments, with no
    experimental annotation. Tracked in projects/FUNCTION_KNOWLEDGE_GAPS.md.
suggested_experiments:
- description: >-
    Reconstitute EryCV with its [4Fe-4S] cluster and SAM to determine the actual radical-SAM
    reaction on the TDP-deoxysugar intermediate (e.g. dehydration/deamination vs reduction),
    resolving the ammonia-lyase-vs-reductase annotation conflict.