NaBBL_candidate_FOX2_2

UniProt ID: A0A314LBC4
Organism: Nicotiana attenuata
Review Status: DRAFT
Aliases:
FOX2_2 NaBBL
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Gene Description

NaBBL_candidate_FOX2_2 is a FOX2-branch BBL-family oxidoreductase candidate in Nicotiana attenuata. BBL-family late-pathway involvement is now supported, but FOX2_2 remains one of several unresolved paralogs rather than a uniquely identified nicotine oxidase.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005773 vacuole
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: Vacuolar localization is plausible contextual information.
Reason: The location is reasonable, but it is not the main discriminating evidence for this paralog.
GO:0016491 oxidoreductase activity
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: This parent redox term is too generic for the current pathway model.
Reason: BBL-family proteins are now tied to a specific late oxidation role in nicotine synthesis.
Supporting Evidence:
file:NICAT/NaBBL_candidate_FOX2_2/NaBBL_candidate_FOX2_2-notes.md
The full preprint places a BBL-family enzyme directly in the nicotine synthase cascade as NicGS, with structural support and clear effects on stereoselective product formation.
GO:0050660 flavin adenine dinucleotide binding
IEA
GO_REF:0000002 		ACCEPT
Summary: FAD binding is appropriate for this flavoprotein.
Reason: This is an informative cofactor annotation for a BBL-family oxidoreductase.
GO:0071949 FAD binding
IEA
GO_REF:0000002 		REMOVE
Summary: This term duplicates GO:0050660.
Reason: Use GO:0050660 as the preferred cofactor-binding term and drop the redundant duplicate.
GO:0042179 nicotine biosynthetic process
IEA
GO_REF:0000041 		KEEP AS NON CORE
Summary: FOX2_2 is a plausible nicotine-pathway candidate but not a uniquely resolved one.
Reason: Family-level pathway support is strong, but specific paralog identity in NICAT remains open.
Supporting Evidence:
file:NICAT/NaBBL_candidate_FOX2_2/NaBBL_candidate_FOX2_2-notes.md
FOX2_2 therefore remains a plausible BBL-family paralog to evaluate, but the paper still leaves the exact NICAT paralog mapping unresolved.

Core Functions

FOX2_2 is a BBL-family FAD-linked oxidoreductase candidate for the late nicotine step, but its exact role relative to the other attenuata BBL paralogs is unresolved.

Molecular Function:
oxidoreductase activity
Directly Involved In:
nicotine biosynthetic process
Supporting Evidence:
  • file:NICAT/NaBBL_candidate_FOX2_2/NaBBL_candidate_FOX2_2-notes.md
    The full preprint places a BBL-family enzyme directly in the nicotine synthase cascade as NicGS, with structural support and clear effects on stereoselective product formation.

References

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Suggested Questions for Experts

Q: Is FOX2_2 biochemically capable of the NicGS-like oxidation step or is it a secondary duplicate?

Q: Does FOX2_2 show distinct expression or subfunctionalization compared with the FOX1-derived BBL candidates?

Suggested Experiments

Experiment: Assay FOX2_2 in late-pathway reconstitution with A622, UGT, and BGL components.

Hypothesis: FOX2_2 retains partial BBL-like chemistry but is not the dominant attenuata late oxidase.

Type: pathway reconstitution assay

Experiment: Compare FOX2_2 expression and knockout phenotypes with FOX1_2 across nicotine-inducing conditions.

Hypothesis: FOX2_2 contributes less strongly than the leading BBL2-like anchor.

Type: comparative expression and genetics

Deep Research

OpenAI

(NaBBL_candidate_FOX2_2-deep-research-openai.md)

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📚 Additional Documentation

Notes

(NaBBL_candidate_FOX2_2-notes.md)

NaBBL_candidate_FOX2_2 Notes

  • The full preprint places a BBL-family enzyme directly in the nicotine synthase cascade as NicGS, with structural support and clear effects on stereoselective product formation. [file:projects/NICOTINE_BIOSYNTHESIS/biorxiv-nicotine-glucosylation-notes.md "BBLa = NicGS, an (S)-nicotine glucoside synthase that drives pathway stereoselectivity"; "BBLa/NicGS was solved with FAD and with (S)-nicotine glucoside product"]
  • FOX2_2 therefore remains a plausible BBL-family paralog to evaluate, but the paper still leaves the exact NICAT paralog mapping unresolved. [file:projects/NICOTINE_BIOSYNTHESIS/biorxiv-nicotine-glucosylation-notes.md "For the NICAT project, this paper is therefore strongest for pathway-role assignment and weakest for exact paralog/accession resolution."]

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