Bacterial trans-4-hydroxy-L-proline catabolism to 2-oxoglutarate

A reusable bacterial four-reaction route that converts trans-4-hydroxy-L-proline to 2-oxoglutarate. A PLP-independent epimerase first forms cis-4-hydroxy-D-proline. An FAD-dependent oxidoreductase generates 4-hydroxy-1-pyrroline-2-carboxylate, a deaminase converts that cyclic imine to 2,5-dioxopentanoate and ammonium, and an aldehyde dehydrogenase-family enzyme completes oxidation to 2-oxoglutarate.

MODULE:hydroxyproline_catabolismDRAFTCONCRETEMetabolic Pathwaymodules/hydroxyproline_catabolism.yaml
trans-4-hydroxy-L-proline catabolic processGO:0019470
GO:0019470
trans-4-hydroxy-L-proline catabolic process
GO:0019470 defines the biological-process boundary from trans-4-hydroxy-L-proline toward central metabolism.
PMID:23995642
Amino acid racemization in Pseudomonas putida KT2440
The KT2440 study experimentally characterizes ProR as a hydroxyproline-preferring epimerase and shows growth on hydroxyproline.
strong epimerization activity with hydroxyproline as the substrate
PMID:22833679
Identification and characterization of D-hydroxyproline dehydrogenase and Delta1-pyrroline-4-hydroxy-2-carboxylate deaminase involved in novel L-hydroxyproline metabolism of bacteria: metabolic convergent evolution.
The study directly characterizes the P. putida D-hydroxyproline dehydrogenase and cyclic-imine deaminase and links both activities to hydroxyproline utilization.
Here, we identified and characterized for the first time two novel enzymes, D-hydroxyproline dehydrogenase and Δ(1)-pyrroline-4-hydroxy-2-carboxylate (Pyr4H2C) deaminase
RHEA:21152
4-hydroxyproline 2-epimerase reaction
Rhea 21152 defines reversible interconversion of trans-4-hydroxy-L-proline and cis-4-hydroxy-D-proline.
RHEA:10560
1-pyrroline-4-hydroxy-2-carboxylate deaminase reaction
Rhea 10560 defines hydrolytic deamination of the cyclic imine to 2,5-dioxopentanoate and ammonium.
RHEA:11296
2,5-dioxovalerate dehydrogenase (NADP+) reaction
Rhea 11296 defines terminal oxidation of 2,5-dioxopentanoate to 2-oxoglutarate with NADP+.

The boundary starts with the stereochemical entry reaction and ends at 2-oxoglutarate. Hydroxyproline transport and downstream use of 2-oxoglutarate are outside the module. The oxidase step has no exact GO molecular-function term, so GO:0016645 is used as the closest donor-class parent while the substrate-specific activity remains explicit in the descriptor. No generic cellular location is asserted.

5Nodes
4Parts
0Variant Sets
0Variants
4Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:hydroxyproline_catabolism deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

  • hydroxyproline_epimerase_step → hydroxyproline_oxidase_step [NOT_CHECKED]
    ProR forms the cis-4-hydroxy-D-proline consumed by the oxidase.
  • hydroxyproline_oxidase_step → hydroxyproline_deaminase_step [NOT_CHECKED]
    The oxidase generates the cyclic imine consumed by the deaminase.
  • hydroxyproline_deaminase_step → hydroxyproline_terminal_dehydrogenase_step [NOT_CHECKED]
    The deaminase produces the 2,5-dioxopentanoate oxidized by the terminal dehydrogenase.

Gene-review completeness (4/6 grounded genes reviewed)

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

Gene Review Complete Deep research
PP_1255 Q88NF6 ✓ ✓ ✗
PP_1256 Q88NF5 ✓ ✓ ✗
PP_1257 Q88NF4 ✓ ✓ ✗
proR Q88NF3 ✓ ✓ ✓
KgsD (Acinetobacter baylyi ADP1) Q6FFQ0 ✗ — —
4-hydroxyproline 2-epimerase (Pseudomonas aeruginosa PAO1) Q9I476 ✗ — —

Details

Bacterial trans-4-hydroxy-L-proline catabolismMetabolic Pathwayhydroxyproline_catabolism
trans-4-hydroxy-L-proline catabolic processGO:0019470

Connections

Part 1: hydroxyproline stereochemical entry
trans-4-hydroxy-L-proline epimerizationReactionhydroxyproline_epimerase_step

Annotons

4-hydroxyproline 2-epimerase activity
hydroxyproline_epimerase_activity
Participant: Family: proline-racemase-family 4-hydroxyproline epimerases
Family:
proline-racemase-family 4-hydroxyproline epimerasesInterPro:IPR008794
Representative Members: ProR (Pseudomonas putida KT2440)UniProtKB:Q88NF3 4-hydroxyproline 2-epimerase (Pseudomonas aeruginosa PAO1)UniProtKB:Q9I476

Function

4-hydroxyproline epimerase activityGO:0047580
Substrates: trans-4-hydroxy-L-proline
Products: cis-4-hydroxy-D-proline

Processes

trans-4-hydroxy-L-proline catabolic processGO:0019470

Converts the common trans-L stereoisomer to the cis-D substrate used by the oxidative pathway.

Part 2: cis-4-hydroxy-D-proline oxidation
cis-4-hydroxy-D-proline oxidationReactionhydroxyproline_oxidase_step

Annotons

D-hydroxyproline dehydrogenase activity
hydroxyproline_oxidase_activity
Participant: Family: FAD-dependent D-amino-acid oxidase-like proteins
Family:
FAD-dependent D-amino-acid oxidase-like proteinsPfam:PF01266
Representative Members: PP_1255 (Pseudomonas putida KT2440)UniProtKB:Q88NF6

Function

D-hydroxyproline dehydrogenase activityGO:0016645
Substrates: cis-4-hydroxy-D-proline oxidized electron acceptor
Products: 4-hydroxy-1-pyrroline-2-carboxylate reduced electron acceptor

Processes

trans-4-hydroxy-L-proline catabolic processGO:0019470

Oxidizes the ProR product to the cyclic imine consumed by the deaminase. The physiological electron acceptor remains unresolved.

Part 3: cyclic-imine deamination
4-hydroxy-1-pyrroline-2-carboxylate deaminationReactionhydroxyproline_deaminase_step

Annotons

1-pyrroline-4-hydroxy-2-carboxylate deaminase activity
hydroxyproline_deaminase_activity
Participant: Family: EC 3.5.4.22 hydroxyproline-pathway deaminases
Family:
EC 3.5.4.22 hydroxyproline-pathway deaminases
Representative Members: PP_1257 (Pseudomonas putida KT2440)UniProtKB:Q88NF4

Function

1-pyrroline-4-hydroxy-2-carboxylate deaminase activityGO:0047425
Substrates: 4-hydroxy-1-pyrroline-2-carboxylate water proton
Products: 2,5-dioxopentanoate ammonium

Processes

trans-4-hydroxy-L-proline catabolic processGO:0019470

Releases the substrate nitrogen as ammonium and produces the aldehyde used by the terminal dehydrogenase.

Part 4: terminal oxidation to 2-oxoglutarate
2,5-dioxopentanoate oxidationReactionhydroxyproline_terminal_dehydrogenase_step

Annotons

2,5-dioxovalerate dehydrogenase activity
hydroxyproline_terminal_dehydrogenase_activity
Participant: Family: alpha-ketoglutaric-semialdehyde dehydrogenase subfamily
Family:
alpha-ketoglutaric-semialdehyde dehydrogenase subfamilyInterPro:IPR044151
Representative Members: PP_1256 candidate (Pseudomonas putida KT2440)UniProtKB:Q88NF5 KgsD (Acinetobacter baylyi ADP1)UniProtKB:Q6FFQ0

Function

2,5-dioxovalerate dehydrogenase (NADP+) activityGO:0047533
Substrates: 2,5-dioxopentanoate NADP+ water
Products: 2-oxoglutarate NADPH proton

Processes

trans-4-hydroxy-L-proline catabolic processGO:0019470

Produces 2-oxoglutarate and completes hydroxyproline carbon entry into central metabolism.