YbbO is a classical short-chain dehydrogenase/reductase (SDR) of SDR family 9C (PANTHER PTHR43313), with a Rossmann-fold NAD(P)-binding domain and the conserved Asn-Ser-Tyr-Lys catalytic tetrad (proton acceptor Tyr159). Purified YbbO is a strictly NADPH-dependent aldehyde reductase that reduces a broad range of aliphatic aldehydes (C2 to C18) to primary alcohols, with low turnover on short and medium chains and the highest affinity and efficiency for long-chain (C16-C18) fatty aldehydes; deletion of ybbO abolishes most long-chain fatty alcohol formation in engineered strains. In strains engineered to make retinoids, YbbO also reduces all-trans-retinal to retinol. Its efficiency in yeast is reported inconsistently: it was the most active of three alcohol dehydrogenases screened in one study (95.6% conversion) but left retinal as the major product in another. Retinal reduction echoes the retinol dehydrogenase activity of its vertebrate SDR9C relatives but involves a substrate E. coli does not make. Its physiological substrate and biological role in E. coli are unknown; it is not required for glutaraldehyde tolerance. The ybbO gene lies between cnoX (ybbN) and tesA and is conserved as a one-to-one orthologue across Enterobacterales.
The protein sequence of this entry may not correspond to a single real gene product (for example, two neighbouring genes joined into one model, or a truncated model). Read the name, features and annotations of the entry with this in mind.
WRONG START SITE SUSPECTED ORTHOLOG COMPARISON
P0AFP4 (269 aa) begins 13 residues (MTHKATEILTGKV) upstream of the MQKSVLITG start used by most YbbO orthologues. The extension is found only in the 269-aa models of Escherichia, Shigella and Klebsiella entries, and 34 of 50 YbbO entries lack it. If the upstream start is not used, residue numbering in P0AFP4 (e.g. active-site Tyr159) is 13 higher than in the mature protein. Annotations are unaffected; only coordinates change.
Supported by:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008106 alcohol dehydrogenase (NADP+) activity | IDA PMID:25108218 Toward aldehyde and alkane production by removing aldehyde r... | ACCEPT | Summary: Purified YbbO reduced C2-C10 aldehydes (acetaldehyde, isobutyraldehyde, hexanal, octanal, decanal) with NADPH but not NADH, highest on hexanal and octanal. Reason: Direct in vitro assay of the purified enzyme showing NADPH-dependent aldehyde reduction, the reverse direction of GO:0008106. The activity was about 10-fold lower than that of DkgA and YahK, so short and medium-chain aldehydes are probably not the preferred substrates (long-chain aldehydes are better, PMID:27134112), but the molecular function is directly demonstrated and is the core activity of the protein. Supporting Evidence: PMID:25108218 YbbO showed broad substrate activity toward all the C2–C10 aldehydes with the highest activity toward hexanal and octanal PMID:25108218 Enzymes were also tested for cofactor specificity (NADH and NADPH), and all five appear to be strictly NADPH dependent with the substrates tested. |
| GO:0008106 alcohol dehydrogenase (NADP+) activity | IDA PMID:27134112 Identification of long chain specific aldehyde reductase and... | ACCEPT | Summary: Kinetic characterisation of YbbO as an NADP(H)-dependent aldehyde reductase with C6-C18 aldehydes, best affinity for C18 and best efficiency for C16; deletion removed >90% of long-chain fatty alcohol production in engineered strains, restored by plasmid-borne ybbO. Reason: Independent enzymological evidence for the same activity, extending the substrate range to long-chain fatty aldehydes, where YbbO performs best. Only the abstract is cached, but it states the kinetic study and the cofactor dependence directly, and it agrees with PMID:25108218. Core function. 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. 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. |
| GO:0016491 oxidoreductase activity | IBA GO_REF:0000033 | MODIFY | Summary: Generic oxidoreductase activity inherited from PANTHER node PTN000672121 (PTHR43313, SDR family 9C), which spans vertebrate hydroxysteroid and retinol dehydrogenases and the bacterial YbbO orthogroup. Reason: Correct and phylogenetically sound: YbbO lies inside the SDR9C clade and keeps the cofactor-binding and catalytic motifs. The broad node stops at oxidoreductase because substrates differ across SDR9C, but for YbbO itself the more specific NADPH-dependent aldehyde reductase activity is directly demonstrated (the two IDA rows above), so the general term should be refined to GO:0008106, an is_a descendant the gene already carries. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000672121 SUPPORTS TRANSFER Broad SDR9C node; generic oxidoreductase transfer is correct, and the target has direct experimental evidence for the more specific NADPH-dependent aldehyde reductase activity. Proposed replacements: alcohol dehydrogenase (NADP+) activity Supporting Evidence: PMID:25108218 YbbO showed broad substrate activity toward all the C2–C10 aldehydes with the highest activity toward hexanal and octanal 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. |
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Download this section (compressed HTML)Q: What is the physiological substrate of YbbO? All activity data come from engineered strains overproducing fatty aldehydes or retinal. Does YbbO reduce endogenous lipid-derived aldehydes (for example from phospholipid or acyl-CoA turnover, given the adjacent tesA), or act on a hydroxysteroid-like secondary alcohol as other SDR9C members do?
Q: Is the 13-residue N-terminal extension of P0AFP4 (MTHKATEILTGKV) translated? Most Enterobacterales orthologues, including Salmonella STM0505, start at the equivalent of Met14.
Q: Should all-trans-retinol dehydrogenase (NADP+) activity (GO:0052650) be annotated? Three groups attribute retinal-to-retinol reduction in engineered E. coli to ybbO by deletion or overexpression (PMID:25726762, PMID:34361955, PMID:41093029). Yeast results conflict: ybbO was the most efficient of three screened alcohol dehydrogenases (95.6% conversion, PMID:39307776) in one study, while retinal remained the major product in another (PMID:34850377). The activity has not been assayed with purified enzyme or with a defined cofactor, and it involves a substrate E. coli does not make. It is not annotated here pending a direct assay.
Experiment: Kinetic analysis of purified YbbO with all-trans-retinal (compared with C16 aldehyde by kcat/Km), 4-hydroxynonenal and other lipid-peroxidation aldehydes, and C16/C18 fatty aldehydes, in both reductive (NADPH) and oxidative (NADP+) directions; combined with untargeted metabolomics of a ybbO deletion strain to find accumulating endogenous aldehydes.
Type: biochemical assay and metabolomics
Experiment: N-terminal proteomics (or start-codon mutagenesis with a C-terminal tag) to determine whether translation of ybbO begins at Met1 or Met14.
Type: proteomics
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