ybbO

UniProt ID: Q7CR11
Organism: Salmonella enterica subsp. enterica serovar Typhimurium str. LT2
Review Status: COMPLETE
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Gene Description

ybbO (STM0505) encodes a 256-residue classical short-chain dehydrogenase/reductase (SDR) of SDR family 9C (PANTHER PTHR43313), with an N-terminal Rossmann-fold TGxxxGxG NAD(P)-binding motif and the conserved YxxxK catalytic motif (proton acceptor Tyr146). It is 90.6% identical to Escherichia coli YbbO, an NADPH-dependent aldehyde reductase that reduces a broad range of aliphatic aldehydes (C2 to C18) to the corresponding primary alcohols, with the highest affinity for long-chain (C16-C18) fatty aldehydes. By orthology, Salmonella YbbO is expected to act as an NADPH-dependent aldehyde reductase; its physiological substrate and biological role, possibly the reduction of endogenous lipid-derived aldehydes, have not been established.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0016491 oxidoreductase activity
IBA
GO_REF:0000033 		MODIFY
Summary: Generic oxidoreductase activity propagated from PANTHER node PTN000672121 (PTHR43313, SDR family 9C). The node groups vertebrate 17beta-hydroxysteroid and retinol dehydrogenases with E. coli YbbO (P0AFP4), so the only claim shared across the clade is the generic SDR oxidoreductase activity. Q7CR11 is a classical SDR with intact cofactor-binding and catalytic motifs and is 90.6% identical to E. coli YbbO, which is an experimentally characterised NADPH-dependent aldehyde reductase.
Reason: The IBA is correct and the node placement is sound: Q7CR11 sits inside the PTHR43313 clade, retains the TGxxxGxG cofactor motif and the YxxxK catalytic motif, and there is no sign of loss of activity. But the term is more general than the evidence for this protein supports. Its E. coli orthologue YbbO is a one-to-one orthologue (reciprocal best hit across both full proteomes with a ~6-fold score gap over the nearest SDR paralogues, conserved ybbN-ybbO-tesA-ybbA neighbourhood, 90.6% identity, invariant N105-S133-Y146-K150 tetrad, and only one substitution, the orthologue-variable Y84F, in the predicted active-site pocket). E. coli YbbO reduces C2-C18 aliphatic aldehydes to alcohols with NADPH as the cofactor (PMID:25108218, PMID:27134112), which is the reverse direction of GO:0008106 alcohol dehydrogenase (NADP+) activity, the term EcoCyc assigns to P0AFP4 by IDA. The broad PAINT node legitimately stops at oxidoreductase because substrate specificity differs across SDR9C, but within the enterobacterial YbbO orthogroup the more specific activity is supported. Replace with GO:0008106 (an is_a descendant of GO:0016491).
Propagation Review
Root cause: TERM SCOPING PROBLEM
Failure modes: GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN000672121 SUPPORTS TRANSFER
Broad PTHR43313 (SDR9C) node mixing vertebrate hydroxysteroid/retinol dehydrogenases and E. coli YbbO; generic oxidoreductase transfer is sound, and the target retains the catalytic motifs. A more specific activity is supported only within the YbbO orthogroup.
Supporting Evidence:
PMID:27134112
We found that deletion of ybbO gene, which encodes NADP(+) dependent aldehyde reductase, led to >90% reduction in long chain fatty alcohol production.
PMID:27134112
Enzyme kinetic study revealed that YbbO has wide substrate specificity ranging from C6 to C18 aldehyde, with maximum affinity and efficiency for C18 and C16 chain length aldehyde, respectively.
PMID:25108218
YbbO showed broad substrate activity toward all the C2–C10 aldehydes with the highest activity toward hexanal and octanal
file:SALTY/ybbO/ybbO-bioinformatics/RESULTS.md
Aligned positions: 256; identical: 232; identity over shorter sequence: 90.6%
file:SALTY/ybbO/ybbO-bioinformatics/RESULTS.md
Reciprocal best hit Q7CR11 <-> P0AFP4: True
file:SALTY/ybbO/ybbO-bioinformatics/RESULTS.md
in approximate pocket: 1 Y84F
file:SALTY/ybbO/ybbO-hypotheses/seq-only-blinded-activity/openscientist.md
Verdict: SUPPORTED (as an evidence-transfer / ISS–ISO curation lead).

Core Functions

NADPH-dependent reduction of aliphatic aldehydes (short to long chain) to primary alcohols, inferred from the 90.6%-identical E. coli orthologue YbbO; physiological substrate unknown.

Molecular Function:
alcohol dehydrogenase (NADP+) activity
Supporting Evidence:
  • PMID:27134112
    Enzyme kinetic study revealed that YbbO has wide substrate specificity ranging from C6 to C18 aldehyde, with maximum affinity and efficiency for C18 and C16 chain length aldehyde, respectively.
  • file:SALTY/ybbO/ybbO-bioinformatics/RESULTS.md
    Aligned positions: 256; identical: 232; identity over shorter sequence: 90.6%

References

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Suggested Questions for Experts

Q: What is the physiological aldehyde substrate of YbbO in Salmonella and E. coli? The characterised activities come from engineered aldehyde-overproducing strains; does YbbO detoxify endogenous lipid-peroxidation or fatty aldehydes, or does it act on a hydroxysteroid-like or other secondary-alcohol substrate as its SDR9C relatives do?

Suggested Experiments

Experiment: Purify Salmonella YbbO (STM0505) and measure NADPH-dependent reduction of a panel of aliphatic (C2-C18), unsaturated (e.g. 4-hydroxynonenal) and aromatic aldehydes and the reverse NADP+-dependent oxidation of alcohols, and test growth and survival of a ybbO deletion mutant under aldehyde and oxidative stress and inside macrophages.

Type: biochemical assay and mutant phenotyping

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

gene-annotate dashboard LLM annotation (Dark Protein Atlas) External predictions

View prediction review YAML · ybbO-dashboard-predictions-review.yaml · Review status: COMPLETE

The KBase gene-annotate dashboard predicted "Short-chain dehydrogenase/reductase (SDR) family oxidoreductase, substrate undetermined" with one GO term, GO:0016491 oxidoreductase activity, for Salmonella enterica gene AYCY01000026.1_161 (serovar not stated). The query is scored on Q7CR11, and the taxon above is that accession's. The two sequences are 99.6% identical over all 256 residues, differing only at I244L, a conservative change away from the catalytic residues. The query is a catalytically intact classical SDR: TGxxxGxG cofactor motif at residue 8, NNAG at 80, and YxxxK with Tyr146/Lys150. Its E. coli orthologue YbbO (P0AFP4) is 91.0% identical over the query length by global alignment (233/256). The 90.6% in the companion review is the same comparison for Q7CR11, which matches P0AFP4 at one fewer position. E. coli YbbO is an NADP(+)-dependent aldehyde reductase with kinetics on C6-C18 aldehydes (PMID:27134112), and it was among five new aldehyde reductases found in a 44-candidate screen (PMID:25108218). The prediction is correct but not novel, because GO:0016491 is already in GOA as an IBA. It is also less informative than the orthologue evidence allows: the companion review refines that row to GO:0008106 alcohol dehydrogenase (NADP+) activity.

Source documents: genes/SALTY/ybbO/ybbO-dashboard-prediction-evidence/prediction.json · genes/SALTY/ybbO/ybbO-dashboard-prediction-evidence/identity_results.json

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0016491 oxidoreductase activity GO_MF
CNN — Correct but not novel Review score: 2/2
Prediction method: gene-annotate dashboard LLM annotation (Dark Protein Atlas) · Version: 2026-10-30 snapshot
Review rationale: The prediction is biologically correct. The query is a catalytically intact classical SDR (TGxxxGxG at residue 8, NNAG at 80, Tyr146/Lys150 in the YxxxK motif; identity_results.json). Its 91.0%-identical E. coli orthologue YbbO is an experimentally characterized NADP(+)-dependent aldehyde reductase (PMID:27134112, PMID:25108218). GO:0016491 is already in GOA for Q7CR11 as an IBA, so it is not novel. LSP is not used because GOA holds no more specific curated term. The companion review refines the IBA row to GO:0008106 alcohol dehydrogenase (NADP+) activity by orthology, which this prediction does not capture.
Supporting Evidence:

Deep Research

OpenScientist

(ybbO-hypotheses/seq-only-blinded-activity/openscientist.md)

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📚 Additional Documentation

Notes

(ybbO-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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