Peptidoglycan precursor biosynthesis and lipid II export

A reusable bacterial pathway that converts UDP-N-acetylglucosamine to UDP-MurNAc-pentapeptide, transfers that nucleotide precursor to the undecaprenyl carrier to form lipid I, glycosylates lipid I to form lipid II, and translocates lipid II across the cytoplasmic membrane. D-Ala-D-Ala synthesis is modeled as a convergent input to MurF, and alternative MurE branches represent meso-diaminopimelate- and L-lysine-containing stem peptides. The module ends at lipid II export and does not include glycan polymerization, peptide cross-linking, carrier recycling, or cell-wall remodeling.

MODULE:peptidoglycan_precursor_biosynthesisDRAFTCONCRETEMetabolic Pathwaymodules/peptidoglycan_precursor_biosynthesis.yaml
peptidoglycan biosynthetic processGO:0009252
GO:0009252
peptidoglycan biosynthetic process
GO:0009252 supplies the biological-process scope for nucleotide, lipid-linked, and exported peptidoglycan precursor formation.
file:modules/peptidoglycan_precursor_biosynthesis-deep-research-openscientist.md
OpenScientist research for the reusable peptidoglycan precursor module
The module-level review supports the ordered MurA-to-MurJ pathway, convergent D-Ala-D-Ala input, third-residue variation, and the boundary before glycan polymerization and peptide cross-linking.
file:projects/P_PUTIDA/deep-research/PSEPK__peptidoglycan_precursor_biosynthesis__ppu00550-deep-research-openscientist.md
OpenScientist PSEPK ppu00550 pathway satisfiability review
The species-aware review finds all precursor and lipid II export steps covered, identifies MurJ as a transporter omitted by the KEGG candidate bucket, and distinguishes Ddl paralogs from upstream amino-acid supply.
PMID:42604454
Protein-Protein Interactions Between Peptidoglycan, Lipopolysaccharide, and Phospholipid Biosynthesis Enzymes in Escherichia coli.
Places Escherichia coli MurA in the LapB interactome alongside the lipid A enzymes LpxA, LpxC, and LpxD and the phospholipid enzyme FabZ. The evidence is physical association only, so it grounds the recorded knowledge gap about partitioning of the shared UDP-GlcNAc pool rather than any module part, function, or connection.
MurA interacts not only with LapB but also with the LPS biosynthesis enzymes LpxA, LpxC, and LpxD as well as with the PL biosynthesis enzyme FabZ
13Nodes
10Parts
1Variant Sets
2Variants
11Annotons
9Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✓ present

  • peptidoglycan_precursor_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.

Function consistency and core coverage

18 gene-function check(s) reflected in core functions · 0 conflict(s) · 15 evidence or coverage gap(s) (33 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
murA_activity Escherichia coli K-12 MurA
UniProtKB:P0A749
Family Representative
UDP-N-acetylglucosamine 1-carboxyvinyltransferase activity
GO:0008760
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murA_activity PSEPK MurA
UniProtKB:Q88P88
Family Representative
UDP-N-acetylglucosamine 1-carboxyvinyltransferase activity
GO:0008760
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murB_activity Escherichia coli K-12 MurB
UniProtKB:P08373
Family Representative
UDP-N-acetylmuramate dehydrogenase activity
GO:0008762
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murB_activity PSEPK MurB
UniProtKB:Q88LM5
Family Representative
UDP-N-acetylmuramate dehydrogenase activity
GO:0008762
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murC_activity Escherichia coli K-12 MurC
UniProtKB:P17952
Family Representative
UDP-N-acetylmuramate-L-alanine ligase activity
GO:0008763
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murC_activity PSEPK MurC
UniProtKB:Q88N75
Family Representative
UDP-N-acetylmuramate-L-alanine ligase activity
GO:0008763
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murD_activity Escherichia coli K-12 MurD
UniProtKB:P14900
Family Representative
UDP-N-acetylmuramoylalanine-D-glutamate ligase activity
GO:0008764
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murD_activity PSEPK MurD
UniProtKB:Q88N78
Family Representative
UDP-N-acetylmuramoylalanine-D-glutamate ligase activity
GO:0008764
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murE_dap_activity Escherichia coli K-12 DAP-specific MurE
UniProtKB:P22188
Family Representative
UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase activity
GO:0008765
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murE_dap_activity PSEPK DAP-specific MurE
UniProtKB:Q88N81
Family Representative
UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase activity
GO:0008765
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murE_lysine_activity Staphylococcus aureus L-lysine-specific MurE
UniProtKB:Q2FZP6
Family Representative
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase activity
GO:0047482
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ddl_activity Escherichia coli K-12 DdlB
UniProtKB:P07862
Family Representative
D-alanine-D-alanine ligase activity
GO:0008716
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ddl_activity PSEPK DdlB
UniProtKB:Q88N74
Family Representative
D-alanine-D-alanine ligase activity
GO:0008716
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ddl_activity PSEPK DdlA
UniProtKB:Q88EV6
Family Representative
D-alanine-D-alanine ligase activity
GO:0008716
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murF_activity Escherichia coli K-12 MurF
UniProtKB:P11880
Family Representative
UDP-MurNAc-L-Ala-D-Glu-meso-DAP-D-Ala-D-Ala ligase activity
GO:0008766
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murF_activity PSEPK MurF
UniProtKB:Q88N80
Family Representative
UDP-MurNAc-L-Ala-D-Glu-meso-DAP-D-Ala-D-Ala ligase activity
GO:0008766
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mraY_activity Escherichia coli K-12 MraY
UniProtKB:P0A6W3
Family Representative
phospho-N-acetylmuramoyl-pentapeptide-transferase activity
GO:0008963
Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
mraY_activity PSEPK MraY
UniProtKB:Q88N79
Family Representative
phospho-N-acetylmuramoyl-pentapeptide-transferase activity
GO:0008963
Review Disagreement
The review removes, modifies, or marks this term over-annotated and provides no retained/core support. Review the rationale; rejection of an evidence row alone is not a biological NOT.
murG_activity Escherichia coli K-12 MurG
UniProtKB:P17443
Family Representative
meso-DAP lipid I N-acetylglucosaminyltransferase activity
GO:0051991
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murG_activity PSEPK MurG
UniProtKB:Q88N76
Family Representative
meso-DAP lipid I N-acetylglucosaminyltransferase activity
GO:0051991
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murJ_activity Escherichia coli K-12 MurJ
UniProtKB:P0AF16
Family Representative
lipid-linked peptidoglycan transporter activity
GO:0015648
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murJ_activity PSEPK MurJ
UniProtKB:Q88Q94
Family Representative
lipid-linked peptidoglycan transporter activity
GO:0015648
Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
murA_activity MurA UDP-N-acetylglucosamine 1-carboxyvinyltransferases
Family
UDP-N-acetylglucosamine 1-carboxyvinyltransferase activity
GO:0008760
Family Id Missing
The family has no identifier linking it to a curated family review.
murB_activity MurB UDP-N-acetylmuramate dehydrogenases
Family
UDP-N-acetylmuramate dehydrogenase activity
GO:0008762
Family Id Missing
The family has no identifier linking it to a curated family review.
murC_activity MurC UDP-N-acetylmuramate-L-alanine ligases
Family
UDP-N-acetylmuramate-L-alanine ligase activity
GO:0008763
Family Id Missing
The family has no identifier linking it to a curated family review.
murD_activity MurD UDP-MurNAc-L-Ala-D-Glu ligases
Family
UDP-N-acetylmuramoylalanine-D-glutamate ligase activity
GO:0008764
Family Id Missing
The family has no identifier linking it to a curated family review.
murE_dap_activity meso-diaminopimelate-specific MurE ligases
Family
UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase activity
GO:0008765
Family Id Missing
The family has no identifier linking it to a curated family review.
murE_lysine_activity L-lysine-specific MurE ligases
Family
UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase activity
GO:0047482
Family Id Missing
The family has no identifier linking it to a curated family review.
ddl_activity D-alanine-D-alanine ligases
Family
D-alanine-D-alanine ligase activity
GO:0008716
Family Id Missing
The family has no identifier linking it to a curated family review.
murF_activity MurF UDP-MurNAc-tripeptide-D-Ala-D-Ala ligases
Family
UDP-MurNAc-L-Ala-D-Glu-meso-DAP-D-Ala-D-Ala ligase activity
GO:0008766
Family Id Missing
The family has no identifier linking it to a curated family review.
mraY_activity MraY phospho-MurNAc-pentapeptide transferases
Family
phospho-N-acetylmuramoyl-pentapeptide-transferase activity
GO:0008963
Family Id Missing
The family has no identifier linking it to a curated family review.
murG_activity MurG lipid I N-acetylglucosaminyltransferases
Family
meso-DAP lipid I N-acetylglucosaminyltransferase activity
GO:0051991
Family Id Missing
The family has no identifier linking it to a curated family review.
murJ_activity MurJ/MviN lipid II flippases
Family
lipid-linked peptidoglycan transporter activity
GO:0015648
Family Id Missing
The family has no identifier linking it to a curated family review.

Gene-review completeness (19/22 grounded genes reviewed)

19 complete review(s) · 11 with deep research · 3 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
ddlA Q88EV6 ✓ ✓ ✓
ddlB Q88N74 ✓ ✓ ✓
mraY Q88N79 ✓ ✓ ✓
murA P0A749 ✓ ✓ ✗
murA Q88P88 ✓ ✓ ✓
murB P08373 ✓ ✓ ✗
murB Q88LM5 ✓ ✓ ✓
murC P17952 ✓ ✓ ✗
murC Q88N75 ✓ ✓ ✓
murD P14900 ✓ ✓ ✗
murD Q88N78 ✓ ✓ ✓
murE P22188 ✓ ✓ ✗
murE Q88N81 ✓ ✓ ✓
murF P11880 ✓ ✓ ✗
murF Q88N80 ✓ ✓ ✓
murG P17443 ✓ ✓ ✗
murG Q88N76 ✓ ✓ ✓
murJ P0AF16 ✓ ✓ ✗
murJ Q88Q94 ✓ ✓ ✓
Escherichia coli K-12 DdlB P07862 ✗ — —
Escherichia coli K-12 MraY P0A6W3 ✗ — —
Staphylococcus aureus L-lysine-specific MurE Q2FZP6 ✗ — —

Details

Peptidoglycan precursor biosynthesis and lipid II exportMetabolic Pathwaypeptidoglycan_precursor_biosynthesis
peptidoglycan biosynthetic processGO:0009252

Reviewed Escherichia coli K-12 proteins ground the conserved DAP-containing route, KT2440 representatives preserve traceability to the PSEPK pathway satisfiability audit, and reviewed Staphylococcus aureus MurE grounds the alternative L-lysine branch. MurF, MraY, and MurG use pentapeptide-generic molecular functions so the module remains valid downstream of either MurE branch; species-level gene reviews may use the corresponding stem-specific child terms. No PANTHER family or PAINT ancestral-node identifier is asserted: the checked-in family-member index does not contain most reviewed cross-species exemplars, and the shared MurE family does not distinguish DAP from L-lysine specificity. The module intentionally excludes amino-acid precursor supply, undecaprenyl-carrier synthesis and recycling, SEDS/PBP polymerization and cross-linking, and peptidoglycan remodeling. CANDIDATE ASSESSED, NOT MODELLED: the MurA-centred protein-interaction hub reported for Escherichia coli (PMID:42604454), in which MurA binds the LapB scaffold and the lipid A enzymes LpxA, LpxC, and LpxD as well as the phospholipid enzyme FabZ, is not represented here. It adds no part to this module, since MurA already occupies the enolpyruvyl-transfer step and the other five proteins catalyse no peptidoglycan-precursor reaction, and it cannot be represented as a connection either: connections are scoped to node identifiers within one module document, ModuleConnectionTypeEnum has no physical-association type, and four of the five partners (LapB, LpxA, LpxC, LpxD) are not modelled anywhere in modules/ because there is no lipid A biosynthesis module. Only FabZ is modelled, in type_ii_fatty_acid_synthesis. The finding is recorded above as an evidence item and a knowledge gap. It would become modellable if a lipid A module is created and a functional, not merely physical, consequence of the interactions is demonstrated.

Connections

MurA produces the enolpyruvyl substrate reduced by MurB.
murB_reduction -> murC_l_alanyl_ligation Provides Input For
MurB produces UDP-MurNAc for MurC.
MurC produces the mono-amino-acid precursor for MurD.
MurD produces the dipeptide precursor for MurE.
MurE supplies UDP-MurNAc-tripeptide to MurF.
Ddl supplies the D-Ala-D-Ala substrate to MurF.
MurF produces UDP-MurNAc-pentapeptide for MraY.
MraY produces lipid I for MurG.
MurG produces lipid II for MurJ-mediated export.
Part 1: enolpyruvyl transfer to UDP-GlcNAc
MurA enolpyruvyl transferReactionmurA_enolpyruvyl_transfer

Annotons

UDP-N-acetylglucosamine 1-carboxyvinyltransferase
murA_activity
Participant: Family: MurA UDP-N-acetylglucosamine 1-carboxyvinyltransferases
Family:
MurA UDP-N-acetylglucosamine 1-carboxyvinyltransferases
Representative Members: Escherichia coli K-12 MurAUniProtKB:P0A749 PSEPK MurAUniProtKB:Q88P88

Function

UDP-N-acetylglucosamine 1-carboxyvinyltransferase activityGO:0008760
Substrates: UDP-N-acetylglucosamine phosphoenolpyruvate
Products: UDP-N-acetylglucosamine enolpyruvate phosphate

Commits UDP-GlcNAc to MurNAc precursor synthesis.

Part 2: UDP-MurNAc formation
MurB UDP-MurNAc formationReactionmurB_reduction

Annotons

UDP-N-acetylmuramate dehydrogenase
murB_activity
Participant: Family: MurB UDP-N-acetylmuramate dehydrogenases
Family:
MurB UDP-N-acetylmuramate dehydrogenases
Representative Members: Escherichia coli K-12 MurBUniProtKB:P08373 PSEPK MurBUniProtKB:Q88LM5

Function

UDP-N-acetylmuramate dehydrogenase activityGO:0008762
Substrates: UDP-N-acetylglucosamine enolpyruvate NADPH
Products: UDP-N-acetylmuramate NADP+
Cofactors: FAD

Reduces the enolpyruvyl intermediate to UDP-MurNAc.

Part 3: L-alanine addition
MurC L-alanine ligationReactionmurC_l_alanyl_ligation

Annotons

UDP-N-acetylmuramate-L-alanine ligase
murC_activity
Participant: Family: MurC UDP-N-acetylmuramate-L-alanine ligases
Family:
MurC UDP-N-acetylmuramate-L-alanine ligases
Representative Members: Escherichia coli K-12 MurCUniProtKB:P17952 PSEPK MurCUniProtKB:Q88N75

Function

UDP-N-acetylmuramate-L-alanine ligase activityGO:0008763
Substrates: UDP-N-acetylmuramate L-alanine ATP
Products: UDP-N-acetylmuramoyl-L-alanine ADP phosphate

Adds the first stem-peptide amino acid.

Part 4: D-glutamate addition
MurD D-glutamate ligationReactionmurD_d_glutamyl_ligation

Annotons

UDP-N-acetylmuramoylalanine-D-glutamate ligase
murD_activity
Participant: Family: MurD UDP-MurNAc-L-Ala-D-Glu ligases
Family:
MurD UDP-MurNAc-L-Ala-D-Glu ligases
Representative Members: Escherichia coli K-12 MurDUniProtKB:P14900 PSEPK MurDUniProtKB:Q88N78

Function

UDP-N-acetylmuramoylalanine-D-glutamate ligase activityGO:0008764
Substrates: UDP-N-acetylmuramoyl-L-alanine D-glutamate ATP
Products: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate ADP phosphate

Adds D-glutamate to the growing stem peptide.

Part 5: third stem-residue addition
MurE third stem-residue ligationReactionmurE_third_residue_ligation
Variant set: MurE third-residue specificity by third stem-peptide amino acid (Exactly One)
meso-diaminopimelate-adding MurEReactionmurE_dap_variant

Annotons

MurE meso-diaminopimelate ligase
murE_dap_activity
Participant: Family: meso-diaminopimelate-specific MurE ligases
Family:
meso-diaminopimelate-specific MurE ligases
Representative Members: Escherichia coli K-12 DAP-specific MurEUniProtKB:P22188 PSEPK DAP-specific MurEUniProtKB:Q88N81

Function

UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase activityGO:0008765
Substrates: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate meso-diaminopimelate ATP
Products: UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-diaminopimelate ADP phosphate

Forms a meso-diaminopimelate-containing tripeptide.

L-lysine-adding MurEReactionmurE_lysine_variant

Annotons

MurE L-lysine ligase
murE_lysine_activity
Participant: Family: L-lysine-specific MurE ligases
Family:
L-lysine-specific MurE ligases
Representative Members: Staphylococcus aureus L-lysine-specific MurEUniProtKB:Q2FZP6

Function

UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase activityGO:0047482
Substrates: UDP-N-acetylmuramoyl-L-alanyl-D-glutamate L-lysine ATP
Products: UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-L-lysine ADP phosphate

Forms an L-lysine-containing tripeptide.

Part 6: D-Ala-D-Ala synthesis
D-Ala-D-Ala synthesisReactionddl_dipeptide_synthesis

Annotons

D-alanine-D-alanine ligase
ddl_activity
Participant: Family: D-alanine-D-alanine ligases
Family:
D-alanine-D-alanine ligases
Representative Members: Escherichia coli K-12 DdlBUniProtKB:P07862 PSEPK DdlBUniProtKB:Q88N74 PSEPK DdlAUniProtKB:Q88EV6

Function

D-alanine-D-alanine ligase activityGO:0008716
Substrates: D-alanine D-alanine ATP
Products: D-alanyl-D-alanine ADP phosphate

Supplies the terminal dipeptide used by MurF.

Part 7: UDP-MurNAc-pentapeptide formation
MurF pentapeptide ligationReactionmurF_pentapeptide_ligation

Annotons

UDP-MurNAc-tripeptide-D-Ala-D-Ala ligase
murF_activity
Participant: Family: MurF UDP-MurNAc-tripeptide-D-Ala-D-Ala ligases
Family:
MurF UDP-MurNAc-tripeptide-D-Ala-D-Ala ligases
Representative Members: Escherichia coli K-12 MurFUniProtKB:P11880 PSEPK MurFUniProtKB:Q88N80

Function

UDP-MurNAc-L-Ala-D-Glu-meso-DAP-D-Ala-D-Ala ligase activityGO:0008766
Substrates: UDP-N-acetylmuramoyl-L-alanyl-D-glutamyl-meso-2,6-diaminopimelate D-alanyl-D-alanine ATP
Products: UDP-N-acetylmuramoyl-pentapeptide ADP phosphate

Joins the tripeptide and D-Ala-D-Ala branches. Both representatives are meso-DAP organisms, so the DAP-tripeptide term GO:0008766 is used; the L-Lys-tripeptide sibling GO:0047480 applies to Lys-type (most Gram-positive) MurF orthologs.

Part 8: lipid I formation
MraY lipid I synthesisReactionmraY_lipid_i_synthesis

Annotons

Phospho-MurNAc-pentapeptide transferase
mraY_activity
Participant: Family: MraY phospho-MurNAc-pentapeptide transferases
Family:
MraY phospho-MurNAc-pentapeptide transferases
Representative Members: Escherichia coli K-12 MraYUniProtKB:P0A6W3 PSEPK MraYUniProtKB:Q88N79

Function

phospho-N-acetylmuramoyl-pentapeptide-transferase activityGO:0008963
Substrates: UDP-N-acetylmuramoyl-pentapeptide undecaprenyl phosphate
Products: lipid I UMP

Locations

plasma membraneGO:0005886

Transfers phospho-MurNAc-pentapeptide to the lipid carrier.

Part 9: lipid II formation
MurG lipid II synthesisReactionmurG_lipid_ii_synthesis

Annotons

Lipid I N-acetylglucosaminyltransferase
murG_activity
Participant: Family: MurG lipid I N-acetylglucosaminyltransferases
Family:
MurG lipid I N-acetylglucosaminyltransferases
Representative Members: Escherichia coli K-12 MurGUniProtKB:P17443 PSEPK MurGUniProtKB:Q88N76

Function

meso-DAP lipid I N-acetylglucosaminyltransferase activityGO:0051991
Substrates: lipid I (meso-DAP stem peptide) UDP-N-acetylglucosamine
Products: lipid II (meso-DAP stem peptide) UDP

Locations

plasma membraneGO:0005886

Adds GlcNAc to lipid I to generate lipid II. Both representatives make meso-DAP lipid I, so GO:0051991 is used; the L-Lys sibling GO:0050511 applies to Lys-type (most Gram-positive) MurG orthologs.

Part 10: lipid II translocation
MurJ lipid II exportTransport StepmurJ_lipid_ii_export

Annotons

Lipid-linked peptidoglycan transporter
murJ_activity
Participant: Family: MurJ/MviN lipid II flippases
Family:
MurJ/MviN lipid II flippases
Representative Members: Escherichia coli K-12 MurJUniProtKB:P0AF16 PSEPK MurJUniProtKB:Q88Q94

Function

lipid-linked peptidoglycan transporter activityGO:0015648
Substrates: lipid II on the cytoplasmic membrane leaflet
Products: lipid II on the periplasmic membrane leaflet

Locations

plasma membraneGO:0005886

Exports lipid II for periplasmic polymerization.