DXP-dependent de novo pyridoxal 5'-phosphate biosynthesis

De novo synthesis of pyridoxal 5'-phosphate (PLP, vitamin B6) through the DXP-dependent bacterial pathway. One branch converts D-erythrose 4-phosphate to 3-amino-2-oxopropyl phosphate through Epd, PdxB, SerC, and PdxA. PdxJ then condenses this product with the shared metabolite 1-deoxy-D-xylulose 5-phosphate (DXP) to form pyridoxine 5'-phosphate, and PdxH performs the terminal oxidation to PLP. DXP production is shared with thiamine and isoprenoid metabolism and is outside this module boundary. The route is restricted to a subset of eubacteria, most prominently the Gammaproteobacteria. The alternative DXP-independent PdxS/PdxT pathway and vitamin-B6 salvage are separate modules.

MODULE:pyridoxal_5_phosphate_biosynthesisCOMPLETECONCRETEMetabolic Pathwaymodules/pyridoxal_5_phosphate_biosynthesis.yaml

'de novo' pyridoxal 5'-phosphate biosynthetic processGO:0036001

GO:0036001

'de novo' pyridoxal 5'-phosphate biosynthetic process

The module is grounded in the GO biological process for de novo PLP biosynthesis.

UniPathway:UPA00244

Pyridoxine 5'-phosphate biosynthesis

UniPathway orders the Epd/PdxB/SerC/PdxA/PdxJ branch that forms pyridoxine 5'-phosphate from D-erythrose 4-phosphate and DXP.

file:modules/pyridoxal_5_phosphate_biosynthesis-deep-research-openscientist.md

OpenScientist review of DXP-dependent de novo PLP biosynthesis

Independent retrieval supports the fixed Epd-PdxB-SerC-PdxA-PdxJ-PdxH sequence and treats DXP supply, vitamin-B6 salvage, and the non-homologous PdxS/PdxT route as separate biological systems.

file:interpro/panther/PTHR43148/PTHR43148-review.yaml

PTHR43148 family review (Epd and type I GAPDH-like enzymes)

Epd (SF3) diverged from the GAPDHs of this family; the root GAPDH-activity and glucose-metabolism PAINT nodes need pruning for SF3.

file:interpro/panther/PTHR42938/PTHR42938-review.yaml

PTHR42938 family review (D-isomer 2-hydroxyacid dehydrogenases)

PdxB sits in the mixed SF9 with eukaryotic formate dehydrogenases, so the PdxB-specific InterPro family is used for the module selector.

file:interpro/panther/PTHR43247/PTHR43247-review.yaml

PTHR43247 family review (phosphoserine aminotransferases)

SerC/PSAT family; bacterial SerC also carries out the PLP-pathway phosphohydroxythreonine transamination.

file:interpro/panther/PTHR30004/PTHR30004-review.yaml

PTHR30004 family review (PdxA and paralogs)

PdxA activity is scoped to SF5; SF6 and SF3 mix PdxA with PdxA2, TphB and ClxD paralogs.

file:interpro/panther/PTHR30456/PTHR30456-review.yaml

PTHR30456 family review (PdxJ)

A single coherent PdxJ subfamily with a bacterial-root PAINT node.

file:interpro/panther/PTHR10851/PTHR10851-review.yaml

PTHR10851 family review (PdxH/PNPO)

PNP/PMP oxidase activity holds for SF0 apart from three PhzG-type phenazine synthases.

file:projects/P_PUTIDA/data/psepk_pathway_membership.tsv

PSEPK pathway membership table

The deterministic pathway partition supplies the PSEPK accessions and locus tags used for the six pathway-instance exemplars.

7Nodes

6Parts

0Variant Sets

0Variants

6Annotons

5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

pyridoxal_5_phosphate_biosynthesis-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.

Reaction chaining (advisory)

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

epd_step → pdxB_step [NOT_CHECKED]
pdxB_step → serC_step [NOT_CHECKED]
serC_step → pdxA_step [NOT_CHECKED]
pdxA_step → pdxJ_step [NOT_CHECKED]
pdxJ_step → pdxH_step [NOT_CHECKED]

Function consistency and core coverage

12 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (18 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
epd_activity	epd (Escherichia coli K-12) UniProtKB:P0A9B6 Family Representative	erythrose-4-phosphate dehydrogenase activity GO:0048001	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
epd_activity	epd (Pseudomonas putida KT2440) UniProtKB:Q88D63 Family Representative	erythrose-4-phosphate dehydrogenase activity GO:0048001	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxB_activity	pdxB (Escherichia coli K-12) UniProtKB:P05459 Family Representative	4-phosphoerythronate dehydrogenase activity GO:0033711	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxB_activity	pdxB (Pseudomonas putida KT2440) UniProtKB:Q88L20 Family Representative	4-phosphoerythronate dehydrogenase activity GO:0033711	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serC_activity	serC (Escherichia coli K-12) UniProtKB:P23721 Family Representative	phosphohydroxythreonine aminotransferase activity GO:0008483	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
serC_activity	serC (Pseudomonas putida KT2440) UniProtKB:Q88M07 Family Representative	phosphohydroxythreonine aminotransferase activity GO:0008483	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxA_activity	pdxA (Escherichia coli K-12) UniProtKB:P19624 Family Representative	4-hydroxythreonine-4-phosphate dehydrogenase activity GO:0050570	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxA_activity	pdxA (Pseudomonas putida KT2440) UniProtKB:Q88QT5 Family Representative	4-hydroxythreonine-4-phosphate dehydrogenase activity GO:0050570	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxJ_activity	pdxJ (Escherichia coli K-12) UniProtKB:P0A794 Family Representative	pyridoxine 5'-phosphate synthase activity GO:0033856	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxJ_activity	pdxJ (Pseudomonas putida KT2440) UniProtKB:Q88MY2 Family Representative	pyridoxine 5'-phosphate synthase activity GO:0033856	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxH_activity	pdxH (Escherichia coli K-12) UniProtKB:P0AFI7 Family Representative	pyridoxamine phosphate oxidase activity GO:0004733	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
pdxH_activity	pdxH (Pseudomonas putida KT2440) UniProtKB:Q88NS5 Family Representative	pyridoxamine phosphate oxidase activity GO:0004733	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
epd_activity	bacterial Epd family NCBIfam:TIGR01532 Family	erythrose-4-phosphate dehydrogenase activity GO:0048001	Family Review Missing No supported structured family review is available for NCBIfam:TIGR01532.
pdxB_activity	PdxB erythronate-4-phosphate dehydrogenase family InterPro:IPR020921 Family	4-phosphoerythronate dehydrogenase activity GO:0033711	Family Review Missing No supported structured family review is available for InterPro:IPR020921.
serC_activity	SerC phosphoserine aminotransferase family PANTHER:PTHR43247:SF1 Family	phosphohydroxythreonine aminotransferase activity GO:0008483	Family Supported Family review supports GO:0004648 FAMILY_WIDE. Asserted by serine_biosynthesis_one_carbon and phosphorylated_serine_biosynthesis; accepted by every reviewed member, including E. coli and P. putida SerC. The pyridoxal_5_phosphate_biosynthesis module uses SF1 for SerC's separate phosphohydroxythreonine reaction, grounded on the parent transaminase term because GO has no specific term for it.
pdxA_activity	PdxA family PANTHER:PTHR30004:SF5 Family	4-hydroxythreonine-4-phosphate dehydrogenase activity GO:0050570	Family Supported Family review supports GO:0050570 for PANTHER:PTHR30004:SF5. SF5 is uniformly PdxA and holds both characterized members used by the DXP-dependent PLP biosynthesis module. SF6 also contains many PdxA-named proteins, but it mixes them with PdxA2 and TphB paralogs that act on other substrates, so the activity is not asserted for SF6 or SF3 as a whole.
pdxJ_activity	PdxJ family PANTHER:PTHR30456:SF0 Family	pyridoxine 5'-phosphate synthase activity GO:0033856	Family Supported Family review supports GO:0033856 FAMILY_WIDE. Single PdxJ subfamily. Accepted as core by the E. coli and P. putida gene reviews, and asserted by the DXP-dependent PLP biosynthesis module.
pdxH_activity	PdxH/PNPO family PANTHER:PTHR10851:SF0 Family	pyridoxamine phosphate oxidase activity GO:0004733	Family Supported Family review supports GO:0004733 for PANTHER:PTHR10851:SF0. SF0, as pyridoxal_5_phosphate_biosynthesis selects; accepted by E. coli and P. putida PdxH, PDX3, SPAC1093.02 and PNPO. The three PhzG-type phenazine synthases in SF0 are excepted. vitamin_b6_plp_metabolism uses the base family, which also takes in the unassessed PPOX2.

Gene-review completeness (12/12 grounded genes reviewed)

12 complete review(s) · 6 with deep research · 0 missing review · 6 reviewed but lacking deep research

Gene	Review	Complete	Deep research
epd P0A9B6	✓	✓	✗
epd Q88D63	✓	✓	✓
pdxA P19624	✓	✓	✗
pdxA Q88QT5	✓	✓	✓
pdxB P05459	✓	✓	✗
pdxB Q88L20	✓	✓	✓
pdxH P0AFI7	✓	✓	✗
pdxH Q88NS5	✓	✓	✓
pdxJ P0A794	✓	✓	✗
pdxJ Q88MY2	✓	✓	✓
serC P23721	✓	✓	✗
serC Q88M07	✓	✓	✓

Tree

DXP-dependent de novo PLP biosynthesisMetabolic Pathwaypyridoxal_5_phosphate_biosynthesis

Parts
1. 1. erythrose 4-phosphate oxidation
2. D-erythrose 4-phosphate to 4-phospho-D-erythronateReactionepd_step
  
  Annotons
  - Erythrose-4-phosphate dehydrogenase Family: bacterial Epd family
3. 2. phosphoerythronate oxidation
4. 4-phospho-D-erythronate to 3-hydroxy-2-oxo-4-phosphooxybutanoateReactionpdxB_step
  
  Annotons
  - PdxB 4-phosphoerythronate dehydrogenase Family: PdxB erythronate-4-phosphate dehydrogenase family
5. 3. phosphohydroxythreonine formation
6. 3-hydroxy-2-oxo-4-phosphooxybutanoate to 4-phosphohydroxy-L-threonineReactionserC_step
  
  Annotons
  - SerC phosphohydroxythreonine aminotransferase Family: SerC phosphoserine aminotransferase family
7. 4. aminoacetone-phosphate formation
8. 4-phosphohydroxy-L-threonine to 3-amino-2-oxopropyl phosphateReactionpdxA_step
  
  Annotons
  - PdxA 4-hydroxythreonine-4-phosphate dehydrogenase Family: PdxA family
9. 5. pyridoxine 5'-phosphate ring formation
10. 3-amino-2-oxopropyl phosphate and DXP to pyridoxine 5'-phosphateReactionpdxJ_step
  
  Annotons
  - PdxJ pyridoxine 5'-phosphate synthase Family: PdxJ family
11. 6. terminal PLP formation
12. Pyridoxine 5'-phosphate to pyridoxal 5'-phosphateReactionpdxH_step
  
  Annotons
  - PdxH pyridoxine/pyridoxamine 5'-phosphate oxidase Family: PdxH/PNPO family

Details

DXP-dependent de novo PLP biosynthesisMetabolic Pathwaypyridoxal_5_phosphate_biosynthesis

'de novo' pyridoxal 5'-phosphate biosynthetic processGO:0036001

The module is defined by reaction chemistry. E. coli K-12, where the pathway was worked out biochemically, supplies the characterized exemplar for every step, and Pseudomonas putida KT2440 is kept as a second gammaproteobacterial instance. The route is lineage-restricted (a subset of eubacteria, chiefly Gammaproteobacteria), so no exemplars from other domains are added. All molecular functions are on leaf annotons, and no generic localization is asserted. Epd and SerC are recruited from central metabolism, and PdxH also acts in vitamin-B6 salvage. GapA can partly substitute for Epd in E. coli (only gapA epd double mutants are pyridoxine auxotrophs), but GapA is not an Epd family member and is not modeled as a part. DXP supply is an upstream input rather than an extra module part. The DXP-independent PdxS/PdxT route and vitamin-B6 salvage are outside this module boundary. GO has no molecular-function term for the SerC phosphohydroxythreonine transamination (RHEA:16573). The serC step is grounded on the parent GO:0008483 transaminase activity rather than on GO:0004648, which defines the separate phosphoserine reaction; the SerC gene reviews carry a proposed phosphohydroxythreonine aminotransferase term. Family notes: Epd and PdxB sit in PANTHER families that mix them with GAPDHs (PTHR43148) and formate dehydrogenases (PTHR42938 SF9), and P. putida Epd has no PANTHER subfamily assignment, so those two steps use the Epd-specific NCBIfam and PdxB-specific InterPro families. SerC, PdxA, PdxJ and PdxH use PANTHER subfamilies whose family reviews cover both representatives.

Connections

epd_step -> pdxB_step Precedes

pdxB_step -> serC_step Precedes

serC_step -> pdxA_step Precedes

pdxA_step -> pdxJ_step Precedes

pdxJ_step -> pdxH_step Precedes

Part 1: erythrose 4-phosphate oxidation

D-erythrose 4-phosphate to 4-phospho-D-erythronateReactionepd_step

Annotons

Erythrose-4-phosphate dehydrogenase

epd_activity

Participant: Family: bacterial Epd family

Family:

bacterial Epd familyNCBIfam:TIGR01532

Representative Members: epd (Escherichia coli K-12)UniProtKB:P0A9B6 epd (Pseudomonas putida KT2440)UniProtKB:Q88D63

Required Function:

erythrose-4-phosphate dehydrogenase activityGO:0048001

Function

erythrose-4-phosphate dehydrogenase activityGO:0048001

Substrates: D-erythrose 4-phosphate NAD+ water

Products: 4-phospho-D-erythronate NADH

Produces the four-carbon phosphoerythronate branch intermediate from pentose-phosphate-pathway-derived erythrose 4-phosphate.

Part 2: phosphoerythronate oxidation

4-phospho-D-erythronate to 3-hydroxy-2-oxo-4-phosphooxybutanoateReactionpdxB_step

Annotons

PdxB 4-phosphoerythronate dehydrogenase

pdxB_activity

Participant: Family: PdxB erythronate-4-phosphate dehydrogenase family

Family:

PdxB erythronate-4-phosphate dehydrogenase familyInterPro:IPR020921

Representative Members: pdxB (Escherichia coli K-12)UniProtKB:P05459 pdxB (Pseudomonas putida KT2440)UniProtKB:Q88L20

Required Function:

4-phosphoerythronate dehydrogenase activityGO:0033711

Function

4-phosphoerythronate dehydrogenase activityGO:0033711

Substrates: 4-phospho-D-erythronate NAD+

Products: (R)-3-hydroxy-2-oxo-4-phosphooxybutanoate NADH

Generates the keto-acid substrate for the following SerC transamination.

Part 3: phosphohydroxythreonine formation

3-hydroxy-2-oxo-4-phosphooxybutanoate to 4-phosphohydroxy-L-threonineReactionserC_step

Annotons

SerC phosphohydroxythreonine aminotransferase

serC_activity

Participant: Family: SerC phosphoserine aminotransferase family

Family:

SerC phosphoserine aminotransferase familyPANTHER:PTHR43247:SF1

Representative Members: serC (Escherichia coli K-12)UniProtKB:P23721 serC (Pseudomonas putida KT2440)UniProtKB:Q88M07

Required Function:

phosphohydroxythreonine aminotransferase activityGO:0008483

Function

phosphohydroxythreonine aminotransferase activityGO:0008483

Substrates: (R)-3-hydroxy-2-oxo-4-phosphooxybutanoate L-glutamate

Products: 4-(phosphooxy)-L-threonine 2-oxoglutarate

Shared SerC chemistry supplies both serine biosynthesis and this PLP-biosynthesis branch; the enzyme is not PLP-pathway-specific.

Part 4: aminoacetone-phosphate formation

4-phosphohydroxy-L-threonine to 3-amino-2-oxopropyl phosphateReactionpdxA_step

Annotons

PdxA 4-hydroxythreonine-4-phosphate dehydrogenase

pdxA_activity

Participant: Family: PdxA family

Family:

PdxA familyPANTHER:PTHR30004:SF5

Representative Members: pdxA (Escherichia coli K-12)UniProtKB:P19624 pdxA (Pseudomonas putida KT2440)UniProtKB:Q88QT5

Required Function:

4-hydroxythreonine-4-phosphate dehydrogenase activityGO:0050570

Function

4-hydroxythreonine-4-phosphate dehydrogenase activityGO:0050570

Substrates: 4-(phosphooxy)-L-threonine NAD+

Products: 3-amino-2-oxopropyl phosphate carbon dioxide NADH

Oxidation followed by spontaneous decarboxylation produces the aminoacetone-phosphate branch substrate used by PdxJ.

Part 5: pyridoxine 5'-phosphate ring formation

3-amino-2-oxopropyl phosphate and DXP to pyridoxine 5'-phosphateReactionpdxJ_step

Annotons

PdxJ pyridoxine 5'-phosphate synthase

pdxJ_activity

Participant: Family: PdxJ family

Family:

PdxJ familyPANTHER:PTHR30456:SF0

Representative Members: pdxJ (Escherichia coli K-12)UniProtKB:P0A794 pdxJ (Pseudomonas putida KT2440)UniProtKB:Q88MY2

Required Function:

pyridoxine 5'-phosphate synthase activityGO:0033856

Function

pyridoxine 5'-phosphate synthase activityGO:0033856

Substrates: 3-amino-2-oxopropyl phosphate 1-deoxy-D-xylulose 5-phosphate

Products: pyridoxine 5'-phosphate phosphate water

Joins the erythrose-derived branch product with the shared DXP input to construct the vitamin-B6 ring.

Part 6: terminal PLP formation

Pyridoxine 5'-phosphate to pyridoxal 5'-phosphateReactionpdxH_step

Annotons

PdxH pyridoxine/pyridoxamine 5'-phosphate oxidase

pdxH_activity

Participant: Family: PdxH/PNPO family

Family:

PdxH/PNPO familyPANTHER:PTHR10851:SF0

Representative Members: pdxH (Escherichia coli K-12)UniProtKB:P0AFI7 pdxH (Pseudomonas putida KT2440)UniProtKB:Q88NS5

Required Function:

pyridoxamine phosphate oxidase activityGO:0004733

Function

pyridoxamine phosphate oxidase activityGO:0004733

Substrates: pyridoxine 5'-phosphate or pyridoxamine 5'-phosphate oxygen

Products: pyridoxal 5'-phosphate hydrogen peroxide

FMN-dependent terminal oxidation produces the active PLP cofactor; the same enzyme also participates in vitamin-B6 salvage.