ADP-heptose precursor biosynthesis

A bacterial nucleotide-sugar pathway that converts D-sedoheptulose 7-phosphate to ADP-D-glycero-beta-D-manno-heptose through GmhA, the kinase activity of HldE, GmhB, and the adenylyltransferase activity of HldE. In lineages that use ADP-L-glycero-beta-D-manno-heptose, HldD performs a subsequent C-6 epimerization. Transfer of the activated heptose into the LPS core by heptosyltransferases is downstream of this module.

MODULE:adp_heptose_biosynthesisDRAFTCONCRETEMetabolic Pathwaymodules/adp_heptose_biosynthesis.yaml
phosphoheptose biosynthetic processGO:2001061 ADP-L,D-heptose biosynthetic processGO:0097171
KEGG:M00064
ADP-L-glycero-D-manno-heptose biosynthesis
Defines the canonical reaction chain from sedoheptulose 7-phosphate to activated L,D-heptose.
GO:0097171
ADP-L-glycero-beta-D-manno-heptose biosynthetic process
Defines the canonical biological process represented by the complete route.
GO:2001061
D-glycero-D-manno-heptose 7-phosphate biosynthetic process
Defines formation of the phosphoheptose intermediate at the pathway entrance.
file:projects/P_PUTIDA/deep-research/PSEPK__adp-heptose-biosynthesis__ppu00541-deep-research-openscientist.md
OpenScientist PSEPK ADP-heptose biosynthesis synthesis
Species-aware retrieval used to distinguish the core ADP-D,D-heptose reactions from terminal HldD-dependent stereochemical maturation.
RHEA:27489
phosphoheptose isomerase reaction
Defines GmhA conversion of sedoheptulose 7-phosphate to phosphoheptose anomers.
RHEA:27473
heptose 7-phosphate kinase reaction
Defines the first catalytic activity of HldE.
RHEA:28518
heptose 1,7-bisphosphate 7-phosphatase reaction
Defines GmhB hydrolysis of the C-7 phosphate.
RHEA:27465
heptose 1-phosphate adenylyltransferase reaction
Defines the second catalytic activity of HldE.
RHEA:17577
ADP-heptose 6-epimerase reaction
Defines optional conversion of the D,D activated sugar to the L,D stereoisomer.

HldE is represented at two distinct leaf reactions because its N- and C-terminal domains catalyze non-adjacent pathway steps. Terminal HldD epimerization is optional at this generic boundary so concrete realizations can distinguish ADP-D,D-heptose production from L,D-heptose maturation. No molecular function or generic cytoplasmic location is asserted at module level.

6Nodes
5Parts
0Variant Sets
0Variants
5Annotons
4Connections

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

✗ none found

No MODULE:adp_heptose_biosynthesis 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.

  • gmhA_step → hldE_kinase_step [NOT_CHECKED]
    GmhA produces the beta phosphoheptose substrate consumed by the HldE kinase domain.
  • hldE_kinase_step → gmhB_step [NOT_CHECKED]
    HldE produces heptose 1,7-bisphosphate consumed by GmhB.
  • gmhB_step → hldE_adenylyltransferase_step [NOT_CHECKED]
    GmhB produces heptose 1-phosphate consumed by the HldE adenylyltransferase domain.
  • hldE_adenylyltransferase_step → hldD_step [NOT_CHECKED]
    ADP-D,D-heptose is the direct substrate of optional HldD epimerization.

Gene-review completeness (3/7 grounded genes reviewed)

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

Gene Review Complete Deep research
gmhA Q88N89 ✓ ✓ ✗
gmhB Q88RS0 ✓ 6/7 ✓
hldE Q88D93 ✓ 10/11 ✗
Escherichia coli GmhB P63228 ✗ — —
Escherichia coli HldE P76658 ✗ — —
Pseudomonas aeruginosa GmhA Q9HVZ0 ✗ — —
Pseudomonas aeruginosa HldD Q9HYQ8 ✗ — —

Details

ADP-heptose precursor biosynthesisMetabolic Pathwayadp_heptose_biosynthesis
phosphoheptose biosynthetic processGO:2001061 ADP-L,D-heptose biosynthetic processGO:0097171

Connections

Part 1: phosphoheptose formation
D-sedoheptulose 7-phosphate isomerizationReactiongmhA_step

Annotons

phosphoheptose isomerase
gmhA_activity
Participant: Family: GmhA phosphoheptose isomerase family
Family:
GmhA phosphoheptose isomerase familyInterPro:IPR004515
Representative Members: PSEPK GmhAUniProtKB:Q88N89 Pseudomonas aeruginosa GmhAUniProtKB:Q9HVZ0

Function

D-sedoheptulose 7-phosphate isomerase activityGO:0008968
Substrates: D-sedoheptulose 7-phosphate
Products: D-glycero-alpha-D-manno-heptose 7-phosphate D-glycero-beta-D-manno-heptose 7-phosphate

Processes

phosphoheptose biosynthetic processGO:2001061

Supplies both phosphoheptose anomers from pentose-phosphate pathway carbon.

Part 2: heptose C-1 phosphorylation
heptose 1,7-bisphosphate formationReactionhldE_kinase_step

Annotons

HldE heptose 7-phosphate kinase
hldE_kinase_activity
Participant: Family: bifunctional HldE family
Family:
bifunctional HldE familyPANTHER:PTHR46969:SF1
Representative Members: PSEPK HldEUniProtKB:Q88D93 Escherichia coli HldEUniProtKB:P76658

Function

heptose 7-phosphate kinase activityGO:0033785
Substrates: D-glycero-beta-D-manno-heptose 7-phosphate ATP
Products: D-glycero-beta-D-manno-heptose 1,7-bisphosphate ADP

Processes

ADP-D-glycero-beta-D-manno-heptose biosynthetic process

The N-terminal HldE domain phosphorylates C-1 of the beta phosphoheptose anomer.

Part 3: heptose 7-dephosphorylation
heptose 1-phosphate formationReactiongmhB_step

Annotons

heptose 1,7-bisphosphate 7-phosphatase
gmhB_activity
Participant: Family: GmhB phosphatase family
Family:
GmhB phosphatase familyPANTHER:PTHR42891:SF1
Representative Members: PSEPK GmhBUniProtKB:Q88RS0 Escherichia coli GmhBUniProtKB:P63228

Function

heptose 1,7-bisphosphate 7-phosphatase activityGO:0034200
Substrates: D-glycero-beta-D-manno-heptose 1,7-bisphosphate water
Products: D-glycero-beta-D-manno-heptose 1-phosphate phosphate

Processes

ADP-D-glycero-beta-D-manno-heptose biosynthetic process

Removes the C-7 phosphate while retaining the C-1 phosphate needed for activation.

Part 4: ADP-D,D-heptose formation
heptose 1-phosphate adenylylationReactionhldE_adenylyltransferase_step

Annotons

HldE heptose-1-phosphate adenylyltransferase
hldE_adenylyltransferase_activity
Participant: Family: bifunctional HldE family
Family:
bifunctional HldE familyPANTHER:PTHR46969:SF1
Representative Members: PSEPK HldEUniProtKB:Q88D93 Escherichia coli HldEUniProtKB:P76658

Function

heptose-1-phosphate adenylyltransferase activityGO:0033786
Substrates: D-glycero-beta-D-manno-heptose 1-phosphate ATP
Products: ADP-D-glycero-beta-D-manno-heptose diphosphate

Processes

ADP-D-glycero-beta-D-manno-heptose biosynthetic process

The C-terminal HldE domain generates the activated D,D-heptose donor.

Part 5: optional ADP-L,D-heptose stereochemical maturation (optional)
ADP-heptose C-6 epimerizationReactionhldD_step

Annotons

ADP-heptose 6-epimerase
hldD_activity
Participant: Family: HldD ADP-heptose epimerase subfamily
Family:
HldD ADP-heptose epimerase subfamilyPANTHER:PTHR43103:SF3
Representative Members: Pseudomonas aeruginosa HldDUniProtKB:Q9HYQ8

Function

ADP-glyceromanno-heptose 6-epimerase activityGO:0008712
Substrates: ADP-D-glycero-beta-D-manno-heptose
Products: ADP-L-glycero-beta-D-manno-heptose

Processes

ADP-L,D-heptose biosynthetic processGO:0097171

Required only when the downstream glycoconjugate uses the L,D-heptose stereoisomer.