Bacterial 4-hydroxybutyrate oxidation to succinate

A reusable two-reaction bacterial pathway in which 4-hydroxybutyrate dehydrogenase oxidizes 4-hydroxybutyrate to succinate semialdehyde and a succinate-semialdehyde dehydrogenase oxidizes that intermediate to succinate. The second reaction can use NAD+ or NADP+ depending on enzyme family and organism. Uptake, upstream 4-hydroxybutyrate production, the GABA shunt, and downstream TCA-cycle oxidation are outside the core.

MODULE:bacterial_4_hydroxybutyrate_oxidationDRAFTCONCRETEMetabolic Pathwaymodules/bacterial_4_hydroxybutyrate_oxidation.yaml
file:PSEPK/gbd/gbd-uniprot.txt
UniProtKB entry for PSEPK Gbd
Q88JJ9 is annotated as 4-hydroxybutyrate dehydrogenase.
file:interpro/panther/PTHR11496/PTHR11496-entries.csv
Local PANTHER PTHR11496 family member table
Q59104 is a characterized Cupriavidus necator Gbd exemplar in SF102, while the subfamily also contains proteins with other dehydrogenase and reductase names.
file:PSEPK/sad-I/sad-I-uniprot.txt
UniProtKB entry for PSEPK Sad-I
Q88K05 is a predicted NAD(P)-linked succinate-semialdehyde dehydrogenase candidate with unresolved cofactor preference.
file:PSEPK/sad-II/sad-II-uniprot.txt
UniProtKB entry for PSEPK Sad-II
Q88I50 is a second predicted NAD(P)-linked succinate-semialdehyde dehydrogenase candidate with unresolved cofactor preference.
file:projects/P_PUTIDA/batches/ppu00650_bacterial_4_hydroxybutyrate_oxidation.tsv
Pseudomonas putida KT2440 4-hydroxybutyrate oxidation batch
The focused batch records exact KT2440 candidate implementations and their unresolved pathway assignments.
file:modules/bacterial_4_hydroxybutyrate_oxidation-deep-research-openscientist.md
OpenScientist review of bacterial 4-hydroxybutyrate oxidation
The report supports a two-reaction module and treats Sad/GabD cofactor preference as family-level context requiring target-protein validation.
PMID:32256468
Unraveling 1,4-Butanediol Metabolism in Pseudomonas putida KT2440.
KT2440 can route 4-hydroxybutyrate toward succinate, but the responsible dehydrogenase pair is not resolved in this module.
PMID:7851418
Metabolic pathway for biosynthesis of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) from 4-hydroxybutyrate by Alcaligenes eutrophus.
Enzymic studies support bacterial 4-hydroxybutyrate degradation through succinate semialdehyde and succinate.

Pseudomonas putida KT2440 supplies a candidate Gbd exemplar but current local evidence does not identify whether Sad-I, Sad-II, or another aldehyde dehydrogenase is the physiological partner during 4-hydroxybutyrate utilization. Their inclusion as candidate exemplars records coverage, not proof that only one paralog contributes. PTHR43217 does not reliably resolve NAD versus NADP specificity for the KT2440 Sad candidates. Q88EN2/GabD-II was excluded after its doe-like ectoine-catabolic locus provided a stronger competing substrate hypothesis than the submitted SSADH name. This exclusion records the absence of evidence for a physiological 4-hydroxybutyrate role; it does not establish that Q88EN2 lacks SSADH side activity. The listed KT2440 proteins are a focused product-name/family candidate set, not a proof that every relevant aldehyde dehydrogenase paralog has been enumerated. No additional gene named gabD-I was found in the simple UniProt gene-list query, but the gabD-II suffix should not be interpreted as evidence of completeness. PTHR11496:SF102 is also broader than Gbd: its entries include proteins named as maleylacetate reductases and propanediol, methanol, or threonine dehydrogenases, so membership alone does not establish GO:0047577.

3Nodes
2Parts
0Variant Sets
0Variants
2Annotons
1Connections

Derived QC

Recommended-field compliance

60.0% recommended fields populated
  • module.knowledge_gaps[0] · status (0/1)
  • module.knowledge_gaps[0] · provenance (0/1)

Module deep research

✓ present

  • bacterial_4_hydroxybutyrate_oxidation-deep-research-openscientist.md (openscientist)

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Gene-review completeness (3/4 grounded genes reviewed)

3 complete review(s) · 2 with deep research · 1 missing review · 1 reviewed but lacking deep research

Gene Review Complete Deep research
gbd Q88JJ9 ✓ ✓ ✗
characterized Gbd (Cupriavidus necator) Q59104 ✗ — —
sad-I Q88K05 ✓ ✓ ✓
sad-II Q88I50 ✓ ✓ ✓

Details

Context
bacteriaNCBITaxon:2
Bacterial 4-hydroxybutyrate oxidation to succinateMetabolic Pathwaybacterial_4_hydroxybutyrate_oxidation
Context
bacteriaNCBITaxon:2

Connections

Gbd-produced succinate semialdehyde is oxidized by a Sad-family succinate-semialdehyde dehydrogenase.
Part 1: 4-hydroxybutyrate oxidation
Gbd-dependent succinate-semialdehyde formationReactiongbd_succinate_semialdehyde_formation

Annotons

4-hydroxybutyrate dehydrogenase
gbd_4_hydroxybutyrate_dehydrogenase
Participant: Family: alcohol dehydrogenase 4 subfamily
Family:
alcohol dehydrogenase 4 subfamilyPANTHER:PTHR11496:SF102
Representative Members: Gbd (Pseudomonas putida KT2440)UniProtKB:Q88JJ9 characterized Gbd (Cupriavidus necator)UniProtKB:Q59104

Function

4-hydroxybutyrate dehydrogenase activityGO:0047577
Substrates: 4-hydroxybutyrate NAD+
Products: succinate semialdehyde NADH proton

Produces the shared aldehyde intermediate from 4-hydroxybutyrate.

Part 2: succinate-semialdehyde oxidation
Succinate-semialdehyde oxidation to succinateReactionsad_succinate_formation

Annotons

Sad-family succinate-semialdehyde dehydrogenase candidate
sad_family_activity
Participant: Family: succinate-semialdehyde dehydrogenase Sad family
Family:
succinate-semialdehyde dehydrogenase Sad familyPANTHER:PTHR43217
Representative Members: Sad-I candidate (Pseudomonas putida KT2440)UniProtKB:Q88K05 Sad-II candidate (Pseudomonas putida KT2440)UniProtKB:Q88I50

Function

succinate-semialdehyde dehydrogenase [NAD(P)+] activityGO:0009013
Substrates: succinate semialdehyde NAD(P)+ water
Products: succinate NAD(P)H proton

Predicted to oxidize succinate semialdehyde; NAD versus NADP preference is unresolved for the KT2440 candidates.