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_biosynthesisDRAFTMetabolic 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.
file:PSEPK/murA/murA-ai-review.yaml
PSEPK murA gene review
UniProt identifies Q88P88 as the UDP-N-acetylglucosamine 1-carboxyvinyltransferase that starts MurNAc precursor synthesis.
file:PSEPK/mraY/mraY-ai-review.yaml
PSEPK mraY gene review
The KT2440 review identifies Q88N79 as the membrane phosphotransferase that forms lipid I from UDP-MurNAc-pentapeptide.
file:PSEPK/murJ/murJ-ai-review.yaml
PSEPK murJ gene review
UniProt identifies Q88Q94 as the lipid II flippase that connects cytoplasmic precursor synthesis to periplasmic assembly.
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.

Gene-review completeness (10/12 grounded genes reviewed)

10 complete review(s) · 10 with deep research · 2 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
ddlB Q88N74 ✓ ✓ ✓
mraY Q88N79 ✓ ✓ ✓
murA Q88P88 ✓ ✓ ✓
murB Q88LM5 ✓ ✓ ✓
murC Q88N75 ✓ ✓ ✓
murD Q88N78 ✓ ✓ ✓
murE Q88N81 ✓ ✓ ✓
murF Q88N80 ✓ ✓ ✓
murG Q88N76 ✓ ✓ ✓
murJ Q88Q94 ✓ ✓ ✓
Staphylococcus aureus L-lysine-specific MurE Q2FZP6 ✗ — —
PSEPK DdlA Q88EV6 ✗ — —

Details

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

The module is taxon-neutral but uses exact KT2440 and reviewed Staphylococcus accessions as representative members. MurF, MraY, and MurG use pentapeptide-generic molecular functions here so the module remains valid downstream of either the DAP- or L-lysine-specific MurE branch; species-level gene reviews may use the corresponding stem-specific child terms. The module intentionally excludes amino-acid precursor supply, the undecaprenyl carrier cycle, SEDS/PBP polymerization, and peptidoglycan remodeling so those systems can be curated as separate reusable modules.

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: 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: 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: 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: 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: 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: 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: PSEPK MurFUniProtKB:Q88N80

Function

UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase activityGO:0047480
Substrates: UDP-N-acetylmuramoyl-tripeptide D-alanyl-D-alanine ATP
Products: UDP-N-acetylmuramoyl-pentapeptide ADP phosphate

Joins the tripeptide and D-Ala-D-Ala branches.

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: 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: PSEPK MurGUniProtKB:Q88N76

Function

undecaprenyldiphospho-muramoylpentapeptide beta-N-acetylglucosaminyltransferase activityGO:0050511
Substrates: lipid I UDP-N-acetylglucosamine
Products: lipid II UDP

Locations

plasma membraneGO:0005886

Adds GlcNAc to lipid I to generate lipid II.

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: 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.