Saro_0802

UniProt ID: Q2GA76
Organism: Novosphingobium aromaticivorans (strain ATCC 700278 / DSM 12444 / CCUG 56034 / CIP 105152 / NBRC 16084 / F199)
Review Status: IN PROGRESS
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Gene Description

Saro_0802 encodes NOV1, a bacterial resveratrol-cleaving dioxygenase (stilbene cleavage oxygenase, SCO) of Novosphingobium aromaticivorans. It is a non-heme Fe(II) enzyme of the carotenoid cleavage oxygenase (CCO/RPE65) superfamily that oxidatively cleaves the central interphenyl Calpha-Cbeta double bond of stilbenes into two aromatic aldehydes; it has been structurally characterized in complex with the substrate resveratrol and the product vanillin. NOV1 is a seven-bladed beta-propeller with an iron cofactor coordinated by four histidines, and its mechanism proceeds via a side-on ferric-superoxide that reacts with substrate activated by deprotonation of the 4-hydroxyl (4'-OH), making the 4'-OH catalytically essential; NOV1 cleaves a wide range of 4'-hydroxy stilbene-like compounds. It also converts the lignin-derived phenylpropene isoeugenol to vanillin and is of interest for lignin valorization. Despite automated annotations to the contrary, NOV1 is not a carotenoid cleavage enzyme.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0010436 carotenoid dioxygenase activity
IEA
GO_REF:0000118
REMOVE
Summary: Automated (IEA / TreeGrafter) annotation of carotenoid dioxygenase activity. This is the wrong substrate class: NOV1 is a stilbene cleavage oxygenase that cleaves resveratrol (and other 4'-OH stilbenes) and isoeugenol, demonstrated structurally with resveratrol bound (PMID:27911781). The carotenoid term is a TreeGrafter over-propagation from the mixed-specificity CCO family.
Reason: Rule/tree-based over-annotation contradicted by the enzyme's structural and functional characterization as a resveratrol/stilbene dioxygenase. The correct specific term is GO:7770086 (resveratrol dioxygenase activity, RHEA:73735; added go-ontology master Jul 2026); the real activity is already covered generally by GO:0016702. Same substrate-class error as cao-1, here via TreeGrafter (GO_REF:0000118) rather than manual IBA.
Supporting Evidence:
PMID:27911781
Stilbene cleavage oxygenases (SCOs) cleave the central double
PMID:27911781
NOV1 cleaves a wide range of other stilbene-like compounds with a 4'-OH group
GO:0016121 carotene catabolic process
IEA
GO_REF:0000118
MODIFY
Summary: Automated (IEA / TreeGrafter) annotation of carotene catabolic process. Wrong substrate class: NOV1 acts in stilbene / lignin-derived compound catabolism, not carotene catabolism.
Reason: Replace with GO:0046272 (stilbene catabolic process), matching the demonstrated stilbene-cleavage activity. Same TreeGrafter over-propagation as the carotenoid MF term.
Proposed replacements: stilbene catabolic process
Supporting Evidence:
PMID:27911781
Stilbene cleavage oxygenases (SCOs) cleave the central double
GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro-based (IEA) dioxygenase MF term (incorporation of two oxygen atoms). Correct and consistent with the demonstrated stilbene dioxygenase activity of NOV1.
Reason: Accurate general dioxygenase MF; the specific activity (resveratrol/stilbene cleavage) sits under this term.
Supporting Evidence:
PMID:27911781
an iron cofactor coordinated by four histidines

Core Functions

Non-heme Fe(II) stilbene cleavage dioxygenase that oxidatively cleaves the interphenyl Calpha-Cbeta double bond of resveratrol and other 4'-hydroxy stilbenes (and isoeugenol) into aromatic aldehydes. The 4'-OH is catalytically essential (its deprotonation activates the substrate for the side-on ferric-superoxide). GO:0016702 is used here because it is the most specific MF term present in the ontology snapshot this repo validates against; the specific term is GO:7770086 (resveratrol dioxygenase activity, RHEA:73735; go-ontology PR #32332, merged 2026-07-17, live in QuickGO).

Supporting Evidence:
  • PMID:27911781
    activated by deprotonation of a phenol group at position 4 of the substrate

References

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Suggested Questions for Experts

Q: The carotenoid dioxygenase activity/process annotations on NOV1 come from the TreeGrafter rule (GO_REF:0000118); should this rule be corrected so it does not assign carotenoid terms to the stilbene-cleaving (SCO) branch of the CCO family?

Suggested Experiments

Experiment: Comparative substrate-panel + structural analysis of NOV1 versus CAO-1 to test whether the wider 4'-hydroxy-stilbene tolerance of NOV1 reflects a more open binding cleft than CAO-1's two-anchor (4'-OH -> Tyr/Lys; 3/5-OH -> Glu) pocket.

πŸ“š Additional Documentation

Notes

(Saro_0802-notes.md)

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