ADP-heptose precursor biosynthesis

ADP-manno-heptose precursor synthesis converts sedoheptulose 7-phosphate into ADP-D-glycero-beta-D-manno-heptose through isomerization, C-1 phosphorylation, C-7 dephosphorylation and adenylylation. A further C-6 epimerization supplies the L,D stereoisomer where required. The same reaction sequence is implemented by separate, bifunctional or trifunctional enzymes and supplies Gram-negative lipopolysaccharide and selected Gram-positive secondary metabolites. An archaeal enzyme set also produces ADP-heptose in an engineered archaeal host; native biological uses outside bacteria remain unresolved.

MODULE:adp_heptose_biosynthesisCOMPLETECONCRETEMetabolic Pathwaymodules/adp_heptose_biosynthesis.yaml
phosphoheptose biosynthetic processGO:2001061 ADP-L,D-heptose biosynthetic processGO:0097171
PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:32591860
ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.
The review describes split HldA/HldC architecture and patchy ADP-heptose distribution; no universal bacterial or Gram-negative pathway presence is inferred.
In Neisseria species, the bifunctional protein HldE is replaced by two independent enzymes, HldA and HldC
PMID:37317291
A Bittersweet Kiss of Gram-Negative Bacteria: The Role of ADP-Heptose in the Pathogenesis of Infection.
This review distinguishes the kinase, phosphatase, nucleotide-activation and epimerization steps and documents split HldA/HldC implementations.
In certain bacteria species, such as Neisseria meningitidis and Ralstonia eutropha, the functions of the HldE are replaced by the HldA (as the β-D-heptose-7-phosphate kinase)and HldC (β-D-heptose-1-phosphate adenosyltransferase) enzymes
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
The Streptomyces fimbriatus SepB/SepL/SepC enzyme set makes ADP-L,D-manno-heptose for septacidin biosynthesis, demonstrating this route outside Gram-negative LPS synthesis.
we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose
PMID:34632535
A conservative distribution of tridomain NDP-heptose synthetases in actinobacteria.
Some related actinobacterial tridomain proteins lack kinase activity; domain architecture alone cannot establish complete pathway competence.
Enzymatical characterization of the tridomain proteins from different strains showed that they are involved in ADP-D-glycero-β-D-manno-heptose biosynthesis despite the unexpected discovery of kinase activities deficient in some proteins.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
PMID:39558531
NDP-β-d-manno-heptoses are small molecule agonists sensed by the vertebrates to discriminate organisms of different kingdoms.
This author commentary reviews cross-kingdom heptose enzymes and unresolved physiological roles. Its shorthand reference to M. maripaludis S2 is read together with the primary engineered-host experiment rather than as evidence of an endogenous pathway.

Bacteria and Archaea are non-universal envelopes for complete demonstrated enzyme sets. Functional individual enzymes also occur in viruses and eukaryotes, but their partial complements do not establish a complete native route. The archaeal experiment expressed DSM2067 enzymes in HBE-negative Methanococcus maripaludis S2; it is not evidence of endogenous S2 production. The core endpoint is ADP-D,D-manno-heptose; HldD/SepC epimerization is optional only at this generic module boundary and is required in realizations whose downstream product uses the L,D donor. The GDP-alpha-heptose route, HygP-dependent ADP-altro-heptose synthesis, glycan transfer reactions and host ALPK1 signaling are outside this module. The kinase adds phosphate at C-1 despite its substrate-based name; the adenylyltransferase transfers AMP, not ADP. Protein fusions do not collapse nonadjacent reactions. Family labels dominated by HldE or DiaA do not establish all activities on every member: the explicit required function and reviewed representative provide the biological restriction. No unverified PAINT ancestral placement is asserted. The ADP route does not imply ATP-exclusive nucleotidyltransferase specificity: some enzymes also use CTP or UTP. The listed fusion architectures are examples; HldF isomerase/nucleotidyltransferase and HldG phosphatase/nucleotidyltransferase fusions are also reported. Archaeal HldD activity and L,D-heptose production were not demonstrated by the four-gene reconstruction; this does not establish epimerase absence. Archaeal representatives are the DSM2067 locus proteins preserved in dated UniSave records. The kinase has an exact match to the published synthetic construct; the other three are family/domain-and-context assignments, not asserted exact experimental constructs.

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

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

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]
    The isomerase product feeds the C-1 kinase reaction; whether the proteins are separate or fused does not change the metabolite connection.
  • hldE_kinase_step → gmhB_step [NOT_CHECKED]
    The kinase product carries phosphate at C-1 and C-7; the phosphatase removes C-7 before nucleotide activation.
  • gmhB_step → hldE_adenylyltransferase_step [NOT_CHECKED]
    The phosphatase leaves heptose 1-phosphate for HldE/HldC/SepB adenylylation.
  • hldE_adenylyltransferase_step → hldD_step [NOT_CHECKED]
    ADP-D,D-manno-heptose feeds optional C-6 epimerization in L,D-producing realizations.

Function consistency and core coverage

20 gene-function check(s) reflected in core functions · 0 conflict(s) · 0 evidence or coverage gap(s) (28 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.

AnnotonParticipantFunctionAssessment
gmhA_activity gmhA (PSEPK)
UniProtKB:Q88N89
Family Representative 		D-sedoheptulose 7-phosphate isomerase activity
GO:0008968 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhA_activity gmhA (PSEAE)
UniProtKB:Q9HVZ0
Family Representative 		D-sedoheptulose 7-phosphate isomerase activity
GO:0008968 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhA_activity sepB (STRFI)
UniProtKB:A0A2P1G6C0
Family Representative 		D-sedoheptulose 7-phosphate isomerase activity
GO:0008968 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhA_activity gmhA1 (METMI DSM2067)
UniProtKB:A0A2L1CCQ9
Family Representative 		D-sedoheptulose 7-phosphate isomerase activity
GO:0008968 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_kinase_activity hldE (PSEPK)
UniProtKB:Q88D93
Family Representative 		heptose 7-phosphate kinase activity
GO:0033785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_kinase_activity hldE (ECOLI)
UniProtKB:P76658
Family Representative 		heptose 7-phosphate kinase activity
GO:0033785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_kinase_activity hldA (BURCJ)
UniProtKB:B4EB35
Family Representative 		heptose 7-phosphate kinase activity
GO:0033785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_kinase_activity sepB (STRFI)
UniProtKB:A0A2P1G6C0
Family Representative 		heptose 7-phosphate kinase activity
GO:0033785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_kinase_activity hldE_2 (METMI DSM2067)
UniProtKB:A0A2L1CCT7
Family Representative 		heptose 7-phosphate kinase activity
GO:0033785 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhB_activity gmhB (PSEPK)
UniProtKB:Q88RS0
Family Representative 		heptose 1,7-bisphosphate 7-phosphatase activity
GO:0034200 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhB_activity gmhB (ECOLI)
UniProtKB:P63228
Family Representative 		heptose 1,7-bisphosphate 7-phosphatase activity
GO:0034200 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhB_activity sepL (STRFI)
UniProtKB:A0A2P1G6D3
Family Representative 		heptose 1,7-bisphosphate 7-phosphatase activity
GO:0034200 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhB_activity gmhB (METMI DSM2067)
UniProtKB:A0A2L1CCN4
Family Representative 		heptose 1,7-bisphosphate 7-phosphatase activity
GO:0034200 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_adenylyltransferase_activity hldE (PSEPK)
UniProtKB:Q88D93
Family Representative 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_adenylyltransferase_activity hldE (ECOLI)
UniProtKB:P76658
Family Representative 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_adenylyltransferase_activity BPSL0395 (BURPS)
UniProtKB:Q63XZ4
Family Representative 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_adenylyltransferase_activity sepB (STRFI)
UniProtKB:A0A2P1G6C0
Family Representative 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldE_adenylyltransferase_activity hldE_3 (METMI DSM2067)
UniProtKB:A0A2L1CD41
Family Representative 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldD_activity hldD (PSEAE)
UniProtKB:Q9HYQ8
Family Representative 		ADP-glyceromanno-heptose 6-epimerase activity
GO:0008712 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
hldD_activity sepC (STRFI)
UniProtKB:A0A2P1G6C1
Family Representative 		ADP-glyceromanno-heptose 6-epimerase activity
GO:0008712 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gmhA_activity Catalytically active GmhA-like isomerase domains
PANTHER:PTHR30390:SF6
Family 		D-sedoheptulose 7-phosphate isomerase activity
GO:0008968 		Family Supported
Family review supports GO:0008968 for PANTHER:PTHR30390:SF6. Safe for the GmhA isomerases, which PANTHER's own inventory places in SF7 but which UniProt's PANTHER cross-reference places in SF6. Both subfamilies are therefore listed as applicable, because the activity tracks membership of the GmhA group rather than either subfamily label. SF6 is functionally mixed, so this covers its GmhA members only and must not be extended to E. coli DiaA itself, for which no isomerase activity is established.
hldE_kinase_activity HldE/HldA/SepB heptose kinase components
PANTHER:PTHR46969:SF1
Family 		heptose 7-phosphate kinase activity
GO:0033785 		Family Supported
Family review supports GO:0033785 FAMILY_WIDE. The kinase domain is present in every member, fused or split, and the activity is the family's defining function.
hldE_kinase_activity HldE/HldA/SepB heptose kinase components
PANTHER:PTHR30390:SF6
Family 		heptose 7-phosphate kinase activity
GO:0033785 		Family Supported
Family review supports GO:0033785 for PANTHER:PTHR30390:SF6. Family membership here reflects the SIS isomerase domain, which is all that most members have. A subset of SF6, the actinobacterial tridomain NDP-heptose synthetases such as Streptomyces fimbriatus SepB (707 residues, against 184-197 for the single-domain isomerases), additionally carries HldE-like kinase and nucleotidyltransferase domains and performs this step as well; that is why the module lists SF6 under this reaction. The activity is therefore scoped to SF6's tridomain members, never to its single-domain GmhA isomerases, and it must be confirmed per member, because tridomain proteins with a deficient kinase domain are reported in this group.
gmhB_activity GmhB phosphatase family
PANTHER:PTHR42891:SF1
Family 		heptose 1,7-bisphosphate 7-phosphatase activity
GO:0034200 		Family Supported
Family review supports GO:0034200 FAMILY_WIDE. The family has a single functional subfamily and three independent experimental seeds; the activity is the family's defining function.
hldE_adenylyltransferase_activity HldE/HldC/SepB heptose adenylyltransferase components
PANTHER:PTHR46969:SF1
Family 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Family Supported
Family review supports GO:0033786 for PANTHER:PTHR46969:SF1. Applies to members that retain the C-terminal cytidylyltransferase-fold domain. Split HldA kinases lack it and must not carry this activity; their partner HldC supplies it.
hldE_adenylyltransferase_activity HldE/HldC/SepB heptose adenylyltransferase components
PANTHER:PTHR43793:SF2
Family 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Family Supported
Family review supports GO:0033786 for PANTHER:PTHR43793:SF2. The activity of subfamily SF2, whose members PANTHER itself names as D-beta-D-heptose 1-phosphate adenylyltransferases, and the step the module grounds to these proteins. It must not extend to SF1, whose members adenylylate FMN or phosphorylate dephospho-CoA. Note that no PAINT node in this family asserts this activity: the support is PANTHER's own subfamily classification together with the reviewed member genes, not a propagated assertion, which is why the module does not rest its adenylylation step on this family alone.
hldE_adenylyltransferase_activity HldE/HldC/SepB heptose adenylyltransferase components
PANTHER:PTHR30390:SF6
Family 		heptose-1-phosphate adenylyltransferase activity
GO:0033786 		Family Supported
Family review supports GO:0033786 for PANTHER:PTHR30390:SF6. Family membership here reflects the SIS isomerase domain, which is all that most members have. A subset of SF6, the actinobacterial tridomain NDP-heptose synthetases such as Streptomyces fimbriatus SepB (707 residues, against 184-197 for the single-domain isomerases), additionally carries HldE-like kinase and nucleotidyltransferase domains and performs this step as well; that is why the module lists SF6 under this reaction. The activity is therefore scoped to SF6's tridomain members, never to its single-domain GmhA isomerases, and it must be confirmed per member, because tridomain proteins with a deficient kinase domain are reported in this group.
hldD_activity HldD ADP-heptose epimerase subfamily
PANTHER:PTHR43103:SF3
Family 		ADP-glyceromanno-heptose 6-epimerase activity
GO:0008712 		Family Supported
Family review supports GO:0008712 for PANTHER:PTHR43103:SF3. Safe across the HldD/SepC members of SF3, the heptose 6-epimerase subfamily, except the fde-locus FdeJ proteins listed as member exceptions. The separate 4-epimerase subfamily acts on a different sugar and position and must not inherit it.

Gene-review completeness (16/16 grounded genes reviewed)

15 complete review(s) · 1 with deep research · 0 missing review · 15 reviewed but lacking deep research

Gene Review Complete Deep research
BPSL0395 Q63XZ4 ✓ ✓ ✗
gmhA Q88N89 ✓ ✓ ✗
gmhA Q9HVZ0 ✓ 8/10 ✗
gmhA1 A0A2L1CCQ9 ✓ ✓ ✗
gmhB A0A2L1CCN4 ✓ ✓ ✗
gmhB P63228 ✓ ✓ ✗
gmhB Q88RS0 ✓ ✓ ✓
hldA B4EB35 ✓ ✓ ✗
hldD Q9HYQ8 ✓ ✓ ✗
hldE P76658 ✓ ✓ ✗
hldE Q88D93 ✓ ✓ ✗
hldE_2 A0A2L1CCT7 ✓ ✓ ✗
hldE_3 A0A2L1CD41 ✓ ✓ ✗
sepB A0A2P1G6C0 ✓ ✓ ✗
sepC A0A2P1G6C1 ✓ ✓ ✗
sepL A0A2P1G6D3 ✓ ✓ ✗

Details

Context
Bacterial lineages retaining ADP-manno-heptose synthesisNCBITaxon:2 Archaeal lineages with a complete ADP-heptose enzyme complementNCBITaxon:2157
PMID:32591860
ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.
The review describes split HldA/HldC architecture and patchy ADP-heptose distribution; no universal bacterial or Gram-negative pathway presence is inferred.
In Neisseria species, the bifunctional protein HldE is replaced by two independent enzymes, HldA and HldC
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
The Streptomyces fimbriatus SepB/SepL/SepC enzyme set makes ADP-L,D-manno-heptose for septacidin biosynthesis, demonstrating this route outside Gram-negative LPS synthesis.
we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose
PMID:34632535
A conservative distribution of tridomain NDP-heptose synthetases in actinobacteria.
Some related actinobacterial tridomain proteins lack kinase activity; domain architecture alone cannot establish complete pathway competence.
Enzymatical characterization of the tridomain proteins from different strains showed that they are involved in ADP-D-glycero-β-D-manno-heptose biosynthesis despite the unexpected discovery of kinase activities deficient in some proteins.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
PMID:39558531
NDP-β-d-manno-heptoses are small molecule agonists sensed by the vertebrates to discriminate organisms of different kingdoms.
This author commentary reviews cross-kingdom heptose enzymes and unresolved physiological roles. Its shorthand reference to M. maripaludis S2 is read together with the primary engineered-host experiment rather than as evidence of an endogenous pathway.

Species can use different protein architectures or downstream stereoisomer endpoints. Production for septacidin establishes that the route is not confined to organisms making LPS. The later cross-kingdom study supersedes bacteria-only taxonomic framing in older reviews. Presence of partial eukaryotic or viral enzyme sets is not treated as proof of a complete native pathway.

ADP-heptose precursor biosynthesisMetabolic Pathwayadp_heptose_biosynthesis
phosphoheptose biosynthetic processGO:2001061 ADP-L,D-heptose biosynthetic processGO:0097171
Context
Bacterial lineages retaining ADP-manno-heptose synthesisNCBITaxon:2 Archaeal lineages with a complete ADP-heptose enzyme complementNCBITaxon:2157
PMID:32591860
ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.
The review describes split HldA/HldC architecture and patchy ADP-heptose distribution; no universal bacterial or Gram-negative pathway presence is inferred.
In Neisseria species, the bifunctional protein HldE is replaced by two independent enzymes, HldA and HldC
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
The Streptomyces fimbriatus SepB/SepL/SepC enzyme set makes ADP-L,D-manno-heptose for septacidin biosynthesis, demonstrating this route outside Gram-negative LPS synthesis.
we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose
PMID:34632535
A conservative distribution of tridomain NDP-heptose synthetases in actinobacteria.
Some related actinobacterial tridomain proteins lack kinase activity; domain architecture alone cannot establish complete pathway competence.
Enzymatical characterization of the tridomain proteins from different strains showed that they are involved in ADP-D-glycero-β-D-manno-heptose biosynthesis despite the unexpected discovery of kinase activities deficient in some proteins.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
PMID:39558531
NDP-β-d-manno-heptoses are small molecule agonists sensed by the vertebrates to discriminate organisms of different kingdoms.
This author commentary reviews cross-kingdom heptose enzymes and unresolved physiological roles. Its shorthand reference to M. maripaludis S2 is read together with the primary engineered-host experiment rather than as evidence of an endogenous pathway.

Species can use different protein architectures or downstream stereoisomer endpoints. Production for septacidin establishes that the route is not confined to organisms making LPS. The later cross-kingdom study supersedes bacteria-only taxonomic framing in older reviews. Presence of partial eukaryotic or viral enzyme sets is not treated as proof of a complete native pathway.

Connections

PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
HldD performs the subsequent epimerization giving the L,D-heptose donor used in E. coli inner-core LPS.
A previously characterized epimerase, formerly named WaaD (RfaD) and now renamed HldD, completes the pathway to form the ADP-L-beta-D-heptose precursor utilized in the assembly of inner core LPS.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
Part 1: phosphoheptose formation
D-sedoheptulose 7-phosphate isomerizationReactiongmhA_step
PMID:18056714
Structure and function of sedoheptulose-7-phosphate isomerase, a critical enzyme for lipopolysaccharide biosynthesis and a target for antibiotic adjuvants.
GmhA substrate/product-bound structures from E. coli and P. aeruginosa support the first committed isomerization reaction.
Here we report structures of GmhA from Escherichia coli and Pseudomonas aeruginosa in apo, substrate, and product-bound forms
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/gmhA1/gmhA1-record-evidence.yaml
Versioned UniSave source for METMI gmhA1 (A0A2L1CCQ9)
Specific HAMAP/GmhA domain and genomic context support isomerase activity; exact identity to the introduced experimental construct is unverified. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.

Annotons

phosphoheptose isomerase
gmhA_activity
Participant: Family: Catalytically active GmhA-like isomerase domains
Family:
Catalytically active GmhA-like isomerase domains The official subfamily is named DiaA and includes proteins with different activities. Selection additionally requires experimentally or curatorially supported sedoheptulose-7-phosphate isomerase activity. Includes standalone GmhA and the isomerase domain of SepB; no DNA-replication function is inferred for these representatives.
Representative Members: gmhA (PSEPK)UniProtKB:Q88N89 gmhA (PSEAE)UniProtKB:Q9HVZ0 sepB (STRFI)UniProtKB:A0A2P1G6C0 gmhA1 (METMI DSM2067)UniProtKB:A0A2L1CCQ9
Required Function:
D-sedoheptulose 7-phosphate isomerase activityGO:0008968

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.

PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:18056714
Structure and function of sedoheptulose-7-phosphate isomerase, a critical enzyme for lipopolysaccharide biosynthesis and a target for antibiotic adjuvants.
GmhA substrate/product-bound structures from E. coli and P. aeruginosa support the first committed isomerization reaction.
Here we report structures of GmhA from Escherichia coli and Pseudomonas aeruginosa in apo, substrate, and product-bound forms
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
The Streptomyces fimbriatus SepB/SepL/SepC enzyme set makes ADP-L,D-manno-heptose for septacidin biosynthesis, demonstrating this route outside Gram-negative LPS synthesis.
we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/gmhA1/gmhA1-record-evidence.yaml
Versioned UniSave source for METMI gmhA1 (A0A2L1CCQ9)
Specific HAMAP/GmhA domain and genomic context support isomerase activity; exact identity to the introduced experimental construct is unverified. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.
Part 2: heptose C-1 phosphorylation
heptose 1,7-bisphosphate formationReactionhldE_kinase_step
PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:23256532
Structural-functional studies of Burkholderia cenocepacia D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.
Burkholderia HldA and HldC are separate kinase and adenylyltransferase proteins corresponding to the two domains of HldE.
HldA and HldC are homologous to the N- and the C-terminal domains of HldE, respectively.
PMID:23256532
Structural-functional studies of Burkholderia cenocepacia D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.
The assayed monofunctional HldA kinase has structural and catalytic-mutagenesis support; a fused-enzyme family label does not imply an adenylyltransferase activity.
Results of the mutagenesis studies on the in vivo activity of HldA confirm the role of the conserved aspartate, Asp270, as the catalytic residue.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/hldE_2/hldE_2-record-evidence.yaml
Versioned UniSave source for METMI hldE_2 (A0A2L1CCT7)
Exact full-length match to the deposited HldA_MM construct PP708527.1; standalone kinase despite the historical hldE_2 symbol. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.

Annotons

Heptose 7-phosphate kinase
hldE_kinase_activity
Participant: Family: HldE/HldA/SepB heptose kinase components
Family:
HldE/HldA/SepB heptose kinase components These verified family memberships encompass different fusion architectures. The required molecular function restricts membership to proteins retaining this reaction; a BIFUNCTIONAL PROTEIN HLDE label does not imply that a standalone HldA or HldC carries both activities. The PTHR30390:SF6 entry is included specifically for the experimentally characterized fused SepB representative, whose kinase and adenylyltransferase domains provide these additional activities. Standalone GmhA/DiaA proteins fail the required-function restriction and are not selected by membership alone.
Representative Members: hldE (PSEPK)UniProtKB:Q88D93 hldE (ECOLI)UniProtKB:P76658 hldA (BURCJ)UniProtKB:B4EB35 sepB (STRFI)UniProtKB:A0A2P1G6C0 hldE_2 (METMI DSM2067)UniProtKB:A0A2L1CCT7
Required Function:
heptose 7-phosphate kinase activityGO:0033785

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

C-1 phosphorylation is carried out by HldE domain I, a standalone HldA, or the kinase domain of SepB.

PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:23256532
Structural-functional studies of Burkholderia cenocepacia D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.
Burkholderia HldA and HldC are separate kinase and adenylyltransferase proteins corresponding to the two domains of HldE.
HldA and HldC are homologous to the N- and the C-terminal domains of HldE, respectively.
PMID:23256532
Structural-functional studies of Burkholderia cenocepacia D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.
The assayed monofunctional HldA kinase has structural and catalytic-mutagenesis support; a fused-enzyme family label does not imply an adenylyltransferase activity.
Results of the mutagenesis studies on the in vivo activity of HldA confirm the role of the conserved aspartate, Asp270, as the catalytic residue.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/hldE_2/hldE_2-record-evidence.yaml
Versioned UniSave source for METMI hldE_2 (A0A2L1CCT7)
Exact full-length match to the deposited HldA_MM construct PP708527.1; standalone kinase despite the historical hldE_2 symbol. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.
Part 3: heptose 7-dephosphorylation
heptose 1-phosphate formationReactiongmhB_step
PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:25848029
Panoramic view of a superfamily of phosphatases through substrate profiling.
Pseudomonas putida Q88RS0 was assayed directly and dephosphorylates beta-heptose 1,7-bisphosphate; additional in-vitro substrates do not establish additional physiological pathways.
Here, we screened GmhB from Pseudomonas putida (UniProt: Q88RS0 ) and found the enzyme dephosphorylated five substrates including d -glycero- d -manno-α-heptose-1,7(bis)phosphate, fructose 1,6-(bis)phosphate, d -allitol 6-phosphate, 2-deoxy- d -manno-2-octulosonate-8-phosphate, and d -glycero- d -manno-β-heptose-1,7-(bis)phosphate.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/gmhB/gmhB-record-evidence.yaml
Versioned UniSave source for METMI gmhB (A0A2L1CCN4)
Specific GmhB family classification and genomic context support phosphatase activity; exact identity to the introduced experimental construct is unverified. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.

Annotons

heptose 1,7-bisphosphate 7-phosphatase
gmhB_activity
Participant: Family: GmhB phosphatase family
Family:
GmhB phosphatase familyPANTHER:PTHR42891:SF1 Includes standalone GmhB and SepL phosphatases. Beta-heptose substrate competence must be supported; family membership alone does not establish anomer preference or the physiological role of every in-vitro substrate.
Representative Members: gmhB (PSEPK)UniProtKB:Q88RS0 gmhB (ECOLI)UniProtKB:P63228 sepL (STRFI)UniProtKB:A0A2P1G6D3 gmhB (METMI DSM2067)UniProtKB:A0A2L1CCN4
Required Function:
heptose 1,7-bisphosphate 7-phosphatase activityGO:0034200

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.

PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:25848029
Panoramic view of a superfamily of phosphatases through substrate profiling.
Pseudomonas putida Q88RS0 was assayed directly and dephosphorylates beta-heptose 1,7-bisphosphate; additional in-vitro substrates do not establish additional physiological pathways.
Here, we screened GmhB from Pseudomonas putida (UniProt: Q88RS0 ) and found the enzyme dephosphorylated five substrates including d -glycero- d -manno-α-heptose-1,7(bis)phosphate, fructose 1,6-(bis)phosphate, d -allitol 6-phosphate, 2-deoxy- d -manno-2-octulosonate-8-phosphate, and d -glycero- d -manno-β-heptose-1,7-(bis)phosphate.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:32591860
ADP-heptose: a bacterial PAMP detected by the host sensor ALPK1.
Partial gmhB deletion phenotypes in some organisms can reflect alternative phosphatase activity; that does not remove the required dephosphorylation reaction from the pathway.
A partial phenotype may result from functional redundancy to GmhB in ADP-heptose biosynthesis and the existence of a yet-unidentified phosphatase activity capable of dephosphorylating HBP.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/gmhB/gmhB-record-evidence.yaml
Versioned UniSave source for METMI gmhB (A0A2L1CCN4)
Specific GmhB family classification and genomic context support phosphatase activity; exact identity to the introduced experimental construct is unverified. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.
Part 4: ADP-D,D-heptose formation
heptose 1-phosphate adenylylationReactionhldE_adenylyltransferase_step
PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:23256532
Structural-functional studies of Burkholderia cenocepacia D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.
Burkholderia HldA and HldC are separate kinase and adenylyltransferase proteins corresponding to the two domains of HldE.
HldA and HldC are homologous to the N- and the C-terminal domains of HldE, respectively.
PMID:28177319
Expression and crystallographic studies of D-glycero-β-D-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei.
The monofunctional HldC protein transfers AMP from ATP to heptose 1-phosphate, yielding ADP-D,D-heptose and pyrophosphate.
HldC transfers the AMP moiety from ATP to d - glycero -β- d - manno -heptose-1-phosphate and releases ADP- d - glycero -β- d - manno -heptose and pyrophosphate.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/hldE_3/hldE_3-record-evidence.yaml
Versioned UniSave source for METMI hldE_3 (A0A2L1CD41)
RfaE-domain-II classification and adjacent HBE genes support adenylylation; exact experimental construct mapping and nucleotide promiscuity are unverified. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.

Annotons

Heptose-1-phosphate adenylyltransferase
hldE_adenylyltransferase_activity
Participant: Family: HldE/HldC/SepB heptose adenylyltransferase components
Family:
HldE/HldC/SepB heptose adenylyltransferase components These verified family memberships encompass different fusion architectures. The required molecular function restricts membership to proteins retaining this reaction; a BIFUNCTIONAL PROTEIN HLDE label does not imply that a standalone HldA or HldC carries both activities. The PTHR30390:SF6 entry is included specifically for the experimentally characterized fused SepB representative, whose kinase and adenylyltransferase domains provide these additional activities. Standalone GmhA/DiaA proteins fail the required-function restriction and are not selected by membership alone.
Representative Members: hldE (PSEPK)UniProtKB:Q88D93 hldE (ECOLI)UniProtKB:P76658 BPSL0395 (BURPS)UniProtKB:Q63XZ4 sepB (STRFI)UniProtKB:A0A2P1G6C0 hldE_3 (METMI DSM2067)UniProtKB:A0A2L1CD41
Required Function:
heptose-1-phosphate adenylyltransferase activityGO:0033786

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

AMP transfer to heptose 1-phosphate is carried out by HldE domain II, standalone HldC, or the terminal nucleotidyltransferase domain of SepB.

PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
The E. coli pathway was reconstructed using E. coli HldE/GmhB with Aneurinibacillus thermoaerophilus GmhA, establishing the four connected reactions to ADP-D,D-heptose.
Our results demonstrate that the synthesis of ADP-D-beta-D-heptose in Escherichia coli requires three proteins, GmhA (sedoheptulose 7-phosphate isomerase), HldE (bifunctional D-beta-D-heptose 7-phosphate kinase/D-beta-D-heptose 1-phosphate adenylyltransferase), and GmhB (D,D-heptose 1,7-bisphosphate phosphatase), as well as ATP and the ketose phosphate precursor sedoheptulose 7-phosphate.
PMID:23256532
Structural-functional studies of Burkholderia cenocepacia D-glycero-β-D-manno-heptose 7-phosphate kinase (HldA) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.
Burkholderia HldA and HldC are separate kinase and adenylyltransferase proteins corresponding to the two domains of HldE.
HldA and HldC are homologous to the N- and the C-terminal domains of HldE, respectively.
PMID:28177319
Expression and crystallographic studies of D-glycero-β-D-manno-heptose-1-phosphate adenylyltransferase from Burkholderia pseudomallei.
The monofunctional HldC protein transfers AMP from ATP to heptose 1-phosphate, yielding ADP-D,D-heptose and pyrophosphate.
HldC transfers the AMP moiety from ATP to d - glycero -β- d - manno -heptose-1-phosphate and releases ADP- d - glycero -β- d - manno -heptose and pyrophosphate.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.
PMID:39116220
The β-d-manno-heptoses are immune agonists across kingdoms.
The 2024 primary study extends functional heptose-biosynthetic enzymes beyond bacteria and demonstrates archaeal ADP-heptose production. Full-text interpretation distinguishes an engineered S2 host expressing DSM2067 enzymes from endogenous S2 synthesis and distinguishes partial viral/eukaryotic complements from complete pathways.
We also produced ADP-heptose in archaea and verified its innate immune agonist functions.
file:METMI/hldE_3/hldE_3-record-evidence.yaml
Versioned UniSave source for METMI hldE_3 (A0A2L1CD41)
RfaE-domain-II classification and adjacent HBE genes support adenylylation; exact experimental construct mapping and nucleotide promiscuity are unverified. The historical accession was deleted from current UniProtKB; its dated source record is preserved without substituting a different strain.
Part 5: optional ADP-L,D-heptose stereochemical maturation (optional)
ADP-heptose C-6 epimerizationReactionhldD_step

Terminal epimerization is supported in the bacterial L,D-producing realizations. The archaeal four-gene reconstruction establishes the D,D endpoint, without testing a subsequent HldD reaction.

PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
HldD performs the subsequent epimerization giving the L,D-heptose donor used in E. coli inner-core LPS.
A previously characterized epimerase, formerly named WaaD (RfaD) and now renamed HldD, completes the pathway to form the ADP-L-beta-D-heptose precursor utilized in the assembly of inner core LPS.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.

Annotons

ADP-heptose 6-epimerase
hldD_activity
Participant: Family: HldD ADP-heptose epimerase subfamily
Family:
HldD ADP-heptose epimerase subfamilyPANTHER:PTHR43103:SF3
Representative Members: hldD (PSEAE)UniProtKB:Q9HYQ8 sepC (STRFI)UniProtKB:A0A2P1G6C1
Required Function:
ADP-glyceromanno-heptose 6-epimerase activityGO:0008712

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.

PMID:11751812
Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli.
HldD performs the subsequent epimerization giving the L,D-heptose donor used in E. coli inner-core LPS.
A previously characterized epimerase, formerly named WaaD (RfaD) and now renamed HldD, completes the pathway to form the ADP-L-beta-D-heptose precursor utilized in the assembly of inner core LPS.
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
The Streptomyces fimbriatus SepB/SepL/SepC enzyme set makes ADP-L,D-manno-heptose for septacidin biosynthesis, demonstrating this route outside Gram-negative LPS synthesis.
we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose
PMID:29483275
d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.
SepB supplies the isomerase, kinase and adenylyltransferase reactions, with SepL supplying phosphatase and SepC supplying C-6 epimerase; these experimentally assigned components realize the same five-reaction route with different domain fusion.