murU encodes N-acetylmuramate alpha-1-phosphate uridylyltransferase, an enzyme in the P. putida KT2440 peptidoglycan recycling shortcut. It converts MurNAc-alpha-1-phosphate and UTP to UDP-MurNAc, supplying a cell-wall precursor through a recycling route that bypasses de novo UDP-MurNAc biosynthesis and contributes to intrinsic fosfomycin resistance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0016779
nucleotidyltransferase activity
|
IEA
GO_REF:0000117 |
MARK AS OVER ANNOTATED |
Summary: This parent nucleotidyltransferase term is directionally correct but less informative than the retained uridylyltransferase activity.
Reason: GO:0070569 is the specific child term for the MurU reaction. Falcon deep research confirms MurU is specifically a uridylyltransferase that generates UDP-MurNAc, so the generic nucleotidyltransferase parent is less informative.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
RecName: Full=N-acetylmuramate alpha-1-phosphate uridylyltransferase
file:PSEPK/murU/murU-deep-research-falcon.md
In the retrieved literature corpus, “MurU” is consistently used for the **MurNAc (N-acetylmuramic acid) salvage/recycling uridylyltransferase** that generates UDP-MurNAc downstream of an anomeric MurNAc kinase (AmgK).
|
|
GO:0009254
peptidoglycan turnover
|
IEA
GO_REF:0000041 |
ACCEPT |
Summary: MurU acts in the peptidoglycan recycling shortcut that generates UDP-MurNAc from recycled MurNAc.
Reason: This pathway role is directly supported by the mutant and biochemical evidence.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
PATHWAY: Cell wall biogenesis; peptidoglycan recycling.
file:PSEPK/murU/murU-uniprot.txt
peptidoglycan recycling as part of a cell wall recycling pathway
file:PSEPK/murU/murU-deep-research-falcon.md
The MurU salvage route is biologically important because it provides an **alternate route to UDP-MurNAc** that can **bypass dependence on the de novo MurA/MurB steps** under conditions where de novo synthesis is impaired (e.g., MurA inhibition by fosfomycin), a point emphasized in the labeling-and-rescue framework.
|
|
GO:0000287
magnesium ion binding
|
IDA
PMID:25767118 Crystal Structure of the N-Acetylmuramic Acid α-1-Phosphate ... |
KEEP AS NON CORE |
Summary: Magnesium is a supported cofactor for the uridylyltransferase reaction, but ion binding is ancillary to the catalytic function.
Reason: Retain as non-core cofactor binding.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
|
|
GO:0002134
UTP binding
|
IDA
PMID:25767118 Crystal Structure of the N-Acetylmuramic Acid α-1-Phosphate ... |
KEEP AS NON CORE |
Summary: UTP binding is expected and experimentally supported for this uridylyltransferase, but the biological function is the transferase reaction.
Reason: Retain as substrate/co-substrate binding, not as a core function summary.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
Cannot accept other nucleotide triphosphates (ATP,
|
|
GO:0009254
peptidoglycan turnover
|
IMP
PMID:23831760 A cell wall recycling shortcut that bypasses peptidoglycan d... |
ACCEPT |
Summary: MurU acts in the peptidoglycan recycling shortcut that generates UDP-MurNAc from recycled MurNAc.
Reason: This pathway role is directly supported by the mutant and biochemical evidence.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
PATHWAY: Cell wall biogenesis; peptidoglycan recycling.
file:PSEPK/murU/murU-uniprot.txt
peptidoglycan recycling as part of a cell wall recycling pathway
file:PSEPK/murU/murU-deep-research-falcon.md
The MurU salvage route is biologically important because it provides an **alternate route to UDP-MurNAc** that can **bypass dependence on the de novo MurA/MurB steps** under conditions where de novo synthesis is impaired (e.g., MurA inhibition by fosfomycin), a point emphasized in the labeling-and-rescue framework.
|
|
GO:0070569
uridylyltransferase activity
|
IDA
PMID:23831760 A cell wall recycling shortcut that bypasses peptidoglycan d... |
ACCEPT |
Summary: MurU directly catalyzes uridylyl transfer from UTP to MurNAc-alpha-1-phosphate, so this is the core molecular function.
Reason: The term captures the experimentally supported EC 2.7.7.99 activity.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
EC=2.7.7.99
file:PSEPK/murU/murU-uniprot.txt
Reaction=N-acetyl-alpha-D-muramate 1-phosphate + UDP + H(+) = UDP-N-
|
|
GO:0070569
uridylyltransferase activity
|
IDA
PMID:25767118 Crystal Structure of the N-Acetylmuramic Acid α-1-Phosphate ... |
ACCEPT |
Summary: MurU directly catalyzes uridylyl transfer from UTP to MurNAc-alpha-1-phosphate, so this is the core molecular function.
Reason: The term captures the experimentally supported EC 2.7.7.99 activity.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
EC=2.7.7.99
file:PSEPK/murU/murU-uniprot.txt
Reaction=N-acetyl-alpha-D-muramate 1-phosphate + UDP + H(+) = UDP-N-
|
|
GO:0097172
N-acetylmuramic acid metabolic process
|
IMP
PMID:23831760 A cell wall recycling shortcut that bypasses peptidoglycan d... |
ACCEPT |
Summary: The enzyme directly metabolizes an N-acetylmuramic acid derivative in the recycling route.
Reason: MurU catalyzes conversion of MurNAc-alpha-1-phosphate to UDP-MurNAc.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
Catalyzes the formation of UDP-N-acetylmuramate (UDP-MurNAc),
file:PSEPK/murU/murU-uniprot.txt
a crucial precursor of the bacterial peptidoglycan cell wall, from UTP
|
|
GO:0097367
carbohydrate derivative binding
|
IDA
PMID:25767118 Crystal Structure of the N-Acetylmuramic Acid α-1-Phosphate ... |
KEEP AS NON CORE |
Summary: MurU binds carbohydrate-derived MurNAc-alpha-1-phosphate as substrate; the binding term is valid but less informative than the reaction term.
Reason: Retain as non-core substrate binding.
Supporting Evidence:
file:PSEPK/murU/murU-uniprot.txt
MurNAc-alpha-1P (PubMed:23831760, PubMed:25767118).
|
Q: Under which environmental conditions does MurU-dependent MurNAc salvage materially contribute to peptidoglycan precursor supply or fosfomycin tolerance in KT2440?
Suggested experts: Bacterial cell-wall recycling experts
Experiment: Compare wild type, murU deletion, and complemented strains for growth on exogenous MurNAc, UDP-MurNAc pool sizes, and fosfomycin sensitivity with and without MurNAc supplementation.
Type: cell-wall precursor metabolomics and antibiotic sensitivity assay
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The UniProt target Q88QT2 is annotated as MurU (murU; PP_0406), an N-acetylmuramate α-1-phosphate uridylyltransferase (EC 2.7.7.99) belonging to the nucleotidyltransferase/MurU family (GlmU-like NTP transferase fold). In the retrieved literature corpus, “MurU” is consistently used for the MurNAc (N-acetylmuramic acid) salvage/recycling uridylyltransferase that generates UDP-MurNAc downstream of an anomeric MurNAc kinase (AmgK). (richter2026peptidoglycanrecyclingis pages 3-4, liang2018…labelingof pages 63-69)
Gram-negative bacteria remodel peptidoglycan (PG) continuously, releasing fragments (muropeptides) that can be imported and recycled; this recycling contributes to cell-wall homeostasis and can impact antibiotic responses. A common framework described in recent pathway-level work is: lytic enzymes release 1,6-anhydro-muropeptides, which are imported into the cytoplasm (often via AmpG), where sugar and peptide moieties are processed and re-enter precursor biosynthesis. (richter2026peptidoglycanrecyclingis pages 3-4)
Within this broader recycling landscape, some organisms (classically discussed for Pseudomonas spp.) use a MurU-dependent salvage route to channel MurNAc-derived intermediates back to UDP-MurNAc, rather than routing them through the MurQ etherase pathway that converts MurNAc-6P to GlcNAc-6P. This MurU route is often termed a “MurU shunt/shortcut” in the recycling literature. (richter2026peptidoglycanrecyclingis pages 3-4, richter2026peptidoglycanrecyclingis pages 4-5)
MurU is a uridylyltransferase that converts a MurNAc-phosphate (MurNAc-1P) intermediate into UDP-MurNAc, thereby regenerating the UDP-activated MurNAc precursor that feeds the canonical cytosolic Mur ligase steps (MurC–MurF) toward Park’s nucleotide and ultimately Lipid II. (liang2018…labelingof pages 63-69, liang2018…labelingof pages 10-14)
Direct biochemical evidence in the retrieved corpus comes from work using the P. putida cell-wall recycling enzymes AmgK and MurU in vitro. In these experiments, MurU acts after AmgK (which generates a monophosphate MurNAc intermediate) and converts MurNAc monophosphate intermediates into the corresponding UDP-sugars (UDP-MurNAc derivatives), as detected by high-resolution LC/MS. (liang2018…labelingof pages 63-69)
Although the text provided does not spell out the full stoichiometry, the standard biochemical interpretation consistent with the evidence is:
- MurNAc-α-1-phosphate + UTP → UDP-MurNAc + PPi
MurU’s product is functionally validated in the same experimental system because the resulting UDP-MurNAc derivatives were accepted by downstream MurC–MurF enzymes to generate Park’s nucleotide analogs, demonstrating that MurU’s product is competent for entry into PG precursor assembly. (liang2018…labelingof pages 57-63, liang2018…labelingof pages 63-69)
A key feature relevant to functional annotation is that the P. putida AmgK/MurU pair is promiscuous toward a panel of MurNAc analogs used for chemical biology. After AmgK phosphorylation, MurU converted monophosphate intermediates “1–8” to their respective UDP products by HRLC/MS; several intermediates (1, 3–5) were reportedly produced in >10 mg quantities and isolated for NMR characterization, implying robust acceptance by the enzymatic system. (liang2018…labelingof pages 63-69)
The substrate panel included MurNAc derivatives bearing bioorthogonal handles (e.g., azide/alkyne) and other functional groups; however, not all bulky derivatives were compatible across steps (e.g., some larger tags were not converted by MurU in the summarized table). (liang2018…labelingof pages 57-63, liang2018…labelingof pages 63-69)
Interpretation for annotation: MurU’s physiological substrate is MurNAc-1P (generated by AmgK from imported MurNAc/anhMurNAc-derived intermediates), but the enzyme exhibits practical tolerance for several substitutions on MurNAc, enabling probe generation. (liang2018…labelingof pages 63-69)
The MurU salvage route is biologically important because it provides an alternate route to UDP-MurNAc that can bypass dependence on the de novo MurA/MurB steps under conditions where de novo synthesis is impaired (e.g., MurA inhibition by fosfomycin), a point emphasized in the labeling-and-rescue framework. (liang2018…labelingof pages 10-14, liang2018…labelingof pages 75-79)
No direct subcellular localization experiment (e.g., fractionation, tagging microscopy) for P. putida KT2440 MurU was present in the retrieved text.
However, pathway context strongly supports a cytosolic localization: Gram-negative PG fragments are described as being transported into the cytoplasm for recycling (e.g., via AmpG), and MurU generates UDP-MurNAc, which is a cytosolic precursor used by Mur ligases (MurC–MurF). Thus, MurU is best annotated as a cytoplasmic enzyme acting on MurNAc-phosphate intermediates arising from imported PG turnover products. (richter2026peptidoglycanrecyclingis pages 3-4, liang2018…labelingof pages 10-14)
A 2024 Methods in Molecular Biology chapter provides updated protocols and framing for exploiting AmgK + MurU as a MurNAc salvage module enabling bioorthogonal labeling of bacterial peptidoglycan using azido-MurNAc probes and click chemistry, including verification by mass spectrometry and microscopy workflows. Although the chapter’s primary organism is Tannerella forsythia, it explicitly defines MurU as NAM α-1-phosphate uridylyltransferase acting with AmgK in the salvage pathway and highlights the broader applicability of this enzymatic module as a tool for PG labeling and trafficking studies. Publication date: 2024 (final form available in PMC 2024-10-28). URL/DOI: https://doi.org/10.1007/978-1-0716-3491-2_1. (hyland2024bioorthogonallabelingand pages 1-3)
A 2023 study in Frontiers in Cellular and Infection Microbiology investigated deletions in PG recycling enzymes (AmpD, AnmK) in Acinetobacter baumannii and reported measurable impacts on phenotypes including biofilm formation and twitching motility (reported reductions ~76–78% in twitching in both mutants), along with broader discussion linking recycling pathway disruption to physiology and intrinsic fosfomycin resistance. While not MurU-specific and not in P. putida, this represents current (2023) experimental evidence that perturbing PG recycling enzymes can influence bacterial fitness/virulence traits—supporting the view that recycling pathways (including MurU shunts where present) are physiologically consequential and potential intervention points. Publication date: 2023-01. URL/DOI: https://doi.org/10.3389/fcimb.2022.1064053. (tajuelo2023roleofpeptidoglycan pages 7-9)
The P. putida AmgK/MurU salvage enzymes have been used as an enabling technology for metabolic labeling of the PG carbohydrate core. The approach described in the retrieved corpus uses the ability of AmgK/MurU to produce UDP-MurNAc (and UDP-MurNAc analogs) from exogenous MurNAc derivatives, which then feed into the normal biosynthetic machinery (MurC–MurF) and ultimately into PG. In engineered E. coli contexts expressing P. putida amgK/murU, supplementation with modified MurNAc sugars coupled with click chemistry permits fluorescence-based visualization of PG, including structured illumination microscopy (SIM) workflows and downstream applications (e.g., generation of labeled PG fragments). (liang2018…labelingof pages 10-14, liang2018…labelingof pages 75-79)
The MurU salvage route is conceptually important in antibiotic biology because it can provide a route to maintain UDP-MurNAc supply when MurA is inhibited by fosfomycin, motivating combination strategies that target recycling as a way to prevent bypass. In the retrieved experimental framework, engineered bacteria could sustain growth under fosfomycin when provided MurNAc analogs and the AmgK/MurU pathway. (liang2018…labelingof pages 75-79)
Kinetic characterization in the retrieved corpus reports for AmgK (the upstream kinase paired with MurU) with MurNAc:
- apparent Km = 30.41 ± 5.75 μM
- kcat = 6.58 ± 0.21 s⁻1
It further reports that for 2Az-NAM and 2Alk-NAM, AmgK shows ~10-fold lower catalytic efficiency than for MurNAc, with other bulky derivatives being ~100-fold less efficient. These kinetic values support the plausibility of substantial metabolic flux through the AmgK→MurU salvage module when native MurNAc is available, and also quantify the tradeoffs for probe analogs. (liang2018…labelingof pages 63-69)
In a cell-based assay (engineered E. coli ΔmurQ expressing P. putida AmgK/MurU), growth under 200 μg/mL fosfomycin could be restored by supplementation with 0.2% (w/v) MurNAc derivatives (including 2Az-NAM and 2Alk-NAM). This provides functional evidence that the salvage module can supply sufficient UDP-MurNAc equivalents to sustain PG synthesis and cell growth under MurA inhibition—an experimentally grounded demonstration of pathway capacity. (liang2018…labelingof pages 75-79)
In A. baumannii, deletion of recycling enzymes AmpD or AnmK led to large decreases in twitching motility (reported ~78% and ~76% reduction, respectively) under the study’s conditions, demonstrating that recycling pathway components can strongly influence surface-associated behaviors. (tajuelo2023roleofpeptidoglycan pages 7-9)
Across the retrieved sources, authors consistently frame MurU as a key node connecting cell wall turnover to precursor re-synthesis, and highlight two major implications:
1) Physiology and antibiotic response: recycling pathways can buffer or bypass inhibition of de novo steps (e.g., MurA), implying that recycling contributes to intrinsic or conditional antibiotic tolerance/resistance mechanisms. (liang2018…labelingof pages 75-79, richter2026peptidoglycanrecyclingis pages 3-4)
2) Tool development: enzymatic promiscuity of AmgK/MurU enables chemical biology probes and imaging of PG dynamics in bacteria and potentially in host-associated contexts (e.g., generating fluorescently labeled PG for trafficking studies). (liang2018…labelingof pages 63-69, hyland2024bioorthogonallabelingand pages 1-3)
The following table consolidates the key evidence supporting the functional annotation and uses only statements supported by the retrieved corpus.
| Topic | Key findings | Evidence source (author/year/title) | Publication date | URL/DOI when available | Citation ID(s) |
|---|---|---|---|---|---|
| Identity | UniProt Q88QT2 corresponds to murU / PP_0406 in Pseudomonas putida KT2440 and is described as N-acetylmuramate alpha-1-phosphate uridylyltransferase; pathway literature consistently uses MurU for the MurNAc salvage/MurU shunt enzyme. | Richter et al. 2026, Peptidoglycan recycling is critical for cell division, cell wall integrity, and β-lactam resistance in Caulobacter crescentus; Hyland et al. 2024, Bioorthogonal Labeling and Click-Chemistry-Based Visualization of the Tannerella forsythia Cell Wall | 2026 Apr; 2024 Oct | https://doi.org/10.7554/eLife.109465 ; https://doi.org/10.1007/978-1-0716-3491-2_1 | (richter2026peptidoglycanrecyclingis pages 4-5, hyland2024bioorthogonallabelingand pages 1-3) |
| Enzymatic reaction | MurU acts downstream of AmgK and converts MurNAc monophosphate intermediates to UDP-MurNAc products, i.e. the uridylyltransferase step that regenerates UDP-MurNAc for PG precursor synthesis. | Liang 2018 thesis, …labeling of the carbohydrate core in bacterial peptidoglycan via the Pseudomonas putida cell wall recycling enzymes AmgK and MurU and its applications | 2018 | Not available in snippet; cites Nat Commun 2017 in thesis | (liang2018…labelingof pages 63-69, liang2018…labelingof pages 57-63) |
| Substrate specificity | Purified P. putida AmgK/MurU accepted natural NAM and several modified NAM derivatives. MurU converted monophosphate intermediates 1–8 to UDP products; Table 4 indicates MurU accepted substrates generated from 2-azido-, 2-alkyne-, ketone-, and some photo-crosslinking derivatives, but not all bulky probes (e.g., streptavidin-affinity probes). | Liang 2018 thesis, …labeling of the carbohydrate core in bacterial peptidoglycan via the Pseudomonas putida cell wall recycling enzymes AmgK and MurU and its applications | 2018 | Not available in snippet | (liang2018…labelingof pages 57-63, liang2018…labelingof pages 63-69) |
| Pathway role | MurU is part of a MurNAc salvage / peptidoglycan recycling shortcut that provides another route to UDP-MurNAc from NAM, bypassing de novo MurA/B-dependent synthesis. In Gram-negative recycling, muropeptides are typically imported by AmpG, processed in the cytoplasm, and in MurU-pathway organisms the MurNAc-derived intermediate is returned to UDP-MurNAc. | Liang 2018 thesis, Figure 1.4 description and chapter text; Richter et al. 2026 eLife background | 2018; 2026 Apr | https://doi.org/10.7554/eLife.109465 | (liang2018…labelingof pages 10-14, richter2026peptidoglycanrecyclingis pages 3-4) |
| Localization inference | No direct localization experiment for P. putida MurU was present in the snippets, but pathway context supports a cytosolic role: recycled muropeptides are transported into the cytoplasm via AmpG, then separated/processed, and MurU uses MurNAc-phosphate intermediates to generate UDP-MurNAc for the cytoplasmic precursor pathway. | Richter et al. 2026, Peptidoglycan recycling is critical…; Liang 2018 thesis pathway context | 2026 Apr; 2018 | https://doi.org/10.7554/eLife.109465 | (richter2026peptidoglycanrecyclingis pages 3-4, liang2018…labelingof pages 10-14) |
| Applications | The P. putida AmgK/MurU system was exploited to generate UDP-MurNAc probes and to enable metabolic labeling of bacterial peptidoglycan with azido/alkyne NAM analogs, supporting fluorescence imaging, SIM/STORM, macrophage interaction studies, and production of labeled PG fragments. Related methods papers use heterologous AmgK/MurU expression to label PG in other organisms. | Liang 2018 thesis; Hyland et al. 2024, Bioorthogonal Labeling and Click-Chemistry-Based Visualization of the Tannerella forsythia Cell Wall | 2018; 2024 Oct | https://doi.org/10.1007/978-1-0716-3491-2_1 | (liang2018…labelingof pages 10-14, liang2018…labelingof pages 75-79, hyland2024bioorthogonallabelingand pages 1-3) |
| Quantitative data | For the partner kinase AmgK in the same P. putida pathway, reported kinetics with NAM were Km = 30.41 ± 5.75 μM and kcat = 6.58 ± 0.21 s^-1; 2Az-NAM and 2Alk-NAM showed about 10-fold lower efficiency than NAM. In cell assays, 0.2% (w/v) NAM analogs restored growth of engineered E. coli under 200 μg/mL fosfomycin. These data support flux through the AmgK→MurU salvage route, though MurU-specific kinetics were not given in the snippets. | Liang 2018 thesis, kinetic and growth sections | 2018 | Not available in snippet | (liang2018…labelingof pages 63-69, liang2018…labelingof pages 75-79) |
| Phenotype/pathway context | Pathway perturbation phenotypes in other bacteria support biological importance of MurU-shunt recycling. In A. baumannii, disrupting recycling enzymes increased fosfomycin susceptibility and altered fitness/virulence traits; under the reported conditions morphology was unchanged, interpreted as de novo synthesis still supplying UDP-MurNAc. | Tajuelo et al. 2023, Role of peptidoglycan recycling enzymes AmpD and AnmK in Acinetobacter baumannii virulence features | 2023 Jan | https://doi.org/10.3389/fcimb.2022.1064053 | (tajuelo2023roleofpeptidoglycan pages 7-9) |
Table: This table summarizes the key evidence supporting functional annotation of MurU (Q88QT2/PP_0406) in Pseudomonas putida KT2440, including its enzymatic role, pathway placement, inferred localization, applications, and available quantitative support. It is restricted to findings present in the provided evidence snippets.
view_images was attempted for pathway figures (e.g., the PG biosynthesis schematic describing the AmgK/MurU route), but the tool could not retrieve images from the thesis text chunks; therefore, this report cannot include figure-cropped image citations despite the attempt.murU (Q88QT2; PP_0406) encodes a cytosolic N-acetylmuramate-α-1-phosphate uridylyltransferase (MurU; EC 2.7.7.99) that converts MurNAc-1-phosphate to UDP-MurNAc in the MurNAc salvage (MurU shunt) arm of peptidoglycan recycling, acting downstream of AmgK and upstream of MurC–MurF to regenerate PG precursors; the P. putida AmgK/MurU system shows experimentally demonstrated promiscuity toward several MurNAc analogs enabling metabolic labeling and probe generation. (liang2018…labelingof pages 63-69, liang2018…labelingof pages 10-14)
References
(richter2026peptidoglycanrecyclingis pages 3-4): Pia Richter, Anna Merz, Jacob Biboy, Nicole Paczia, Timo Glatter, Jared Ng, Waldemar Vollmer, and Martin Thanbichler. Peptidoglycan recycling is critical for cell division, cell wall integrity, and β-lactam resistance in caulobacter crescentus. eLife, Apr 2026. URL: https://doi.org/10.7554/elife.109465, doi:10.7554/elife.109465. This article has 1 citations and is from a domain leading peer-reviewed journal.
(liang2018…labelingof pages 63-69): H Liang. … labeling of the carbohydrate core in bacterial peptidoglycan via the pseudomonas putida cell wall recycling enzymes amgk and muru and its applications. Unknown journal, 2018.
(richter2026peptidoglycanrecyclingis pages 4-5): Pia Richter, Anna Merz, Jacob Biboy, Nicole Paczia, Timo Glatter, Jared Ng, Waldemar Vollmer, and Martin Thanbichler. Peptidoglycan recycling is critical for cell division, cell wall integrity, and β-lactam resistance in caulobacter crescentus. eLife, Apr 2026. URL: https://doi.org/10.7554/elife.109465, doi:10.7554/elife.109465. This article has 1 citations and is from a domain leading peer-reviewed journal.
(liang2018…labelingof pages 10-14): H Liang. … labeling of the carbohydrate core in bacterial peptidoglycan via the pseudomonas putida cell wall recycling enzymes amgk and muru and its applications. Unknown journal, 2018.
(liang2018…labelingof pages 57-63): H Liang. … labeling of the carbohydrate core in bacterial peptidoglycan via the pseudomonas putida cell wall recycling enzymes amgk and muru and its applications. Unknown journal, 2018.
(liang2018…labelingof pages 75-79): H Liang. … labeling of the carbohydrate core in bacterial peptidoglycan via the pseudomonas putida cell wall recycling enzymes amgk and muru and its applications. Unknown journal, 2018.
(hyland2024bioorthogonallabelingand pages 1-3): Stephen N. Hyland, Sreedevi Chinthamani, Sushanta Ratna, Kimberly A. Wodzanowski, Liam-Michael D. Sandles, Kiyonobu Honma, Catherine Leimkuhler-Grimes, and Ashu Sharma. Bioorthogonal labeling and click-chemistry-based visualization of the tannerella forsythia cell wall. Methods in molecular biology, 2727:1-16, Oct 2024. URL: https://doi.org/10.1007/978-1-0716-3491-2_1, doi:10.1007/978-1-0716-3491-2_1. This article has 3 citations and is from a peer-reviewed journal.
(tajuelo2023roleofpeptidoglycan pages 7-9): Ana Tajuelo, María C. Terrón, Mireia López-Siles, and Michael J. McConnell. Role of peptidoglycan recycling enzymes ampd and anmk in acinetobacter baumannii virulence features. Frontiers in Cellular and Infection Microbiology, Jan 2023. URL: https://doi.org/10.3389/fcimb.2022.1064053, doi:10.3389/fcimb.2022.1064053. This article has 12 citations.
id: Q88QT2
gene_symbol: murU
product_type: PROTEIN
status: DRAFT
taxon:
id: NCBITaxon:160488
label: Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)
description: murU encodes N-acetylmuramate alpha-1-phosphate uridylyltransferase, an enzyme in the P. putida KT2440 peptidoglycan recycling shortcut. It converts MurNAc-alpha-1-phosphate and UTP to UDP-MurNAc, supplying a cell-wall precursor through a recycling route that bypasses de novo UDP-MurNAc biosynthesis and contributes to intrinsic fosfomycin resistance.
existing_annotations:
- term:
id: GO:0016779
label: nucleotidyltransferase activity
evidence_type: IEA
original_reference_id: GO_REF:0000117
review:
summary: This parent nucleotidyltransferase term is directionally correct but less informative than the retained uridylyltransferase activity.
action: MARK_AS_OVER_ANNOTATED
reason: GO:0070569 is the specific child term for the MurU reaction. Falcon deep research confirms MurU is specifically a uridylyltransferase that generates UDP-MurNAc, so the generic nucleotidyltransferase parent is less informative.
supported_by:
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: 'RecName: Full=N-acetylmuramate alpha-1-phosphate uridylyltransferase'
- reference_id: file:PSEPK/murU/murU-deep-research-falcon.md
supporting_text: |-
In the retrieved literature corpus, “MurU” is consistently used for the **MurNAc (N-acetylmuramic acid) salvage/recycling uridylyltransferase** that generates UDP-MurNAc downstream of an anomeric MurNAc kinase (AmgK).
- term:
id: GO:0009254
label: peptidoglycan turnover
evidence_type: IEA
original_reference_id: GO_REF:0000041
review:
summary: MurU acts in the peptidoglycan recycling shortcut that generates UDP-MurNAc from recycled MurNAc.
action: ACCEPT
reason: This pathway role is directly supported by the mutant and biochemical evidence.
supported_by:
- &id001
reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: 'PATHWAY: Cell wall biogenesis; peptidoglycan recycling.'
- &id002
reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: peptidoglycan recycling as part of a cell wall recycling pathway
- &id003
reference_id: file:PSEPK/murU/murU-deep-research-falcon.md
supporting_text: |-
The MurU salvage route is biologically important because it provides an **alternate route to UDP-MurNAc** that can **bypass dependence on the de novo MurA/MurB steps** under conditions where de novo synthesis is impaired (e.g., MurA inhibition by fosfomycin), a point emphasized in the labeling-and-rescue framework.
- term:
id: GO:0000287
label: magnesium ion binding
evidence_type: IDA
original_reference_id: PMID:25767118
review:
summary: Magnesium is a supported cofactor for the uridylyltransferase reaction, but ion binding is ancillary to the catalytic function.
action: KEEP_AS_NON_CORE
reason: Retain as non-core cofactor binding.
supported_by:
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
- term:
id: GO:0002134
label: UTP binding
evidence_type: IDA
original_reference_id: PMID:25767118
review:
summary: UTP binding is expected and experimentally supported for this uridylyltransferase, but the biological function is the transferase reaction.
action: KEEP_AS_NON_CORE
reason: Retain as substrate/co-substrate binding, not as a core function summary.
supported_by:
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: Cannot accept other nucleotide triphosphates (ATP,
- term:
id: GO:0009254
label: peptidoglycan turnover
evidence_type: IMP
original_reference_id: PMID:23831760
review:
summary: MurU acts in the peptidoglycan recycling shortcut that generates UDP-MurNAc from recycled MurNAc.
action: ACCEPT
reason: This pathway role is directly supported by the mutant and biochemical evidence.
supported_by:
- *id001
- *id002
- *id003
- term:
id: GO:0070569
label: uridylyltransferase activity
evidence_type: IDA
original_reference_id: PMID:23831760
review:
summary: MurU directly catalyzes uridylyl transfer from UTP to MurNAc-alpha-1-phosphate, so this is the core molecular function.
action: ACCEPT
reason: The term captures the experimentally supported EC 2.7.7.99 activity.
supported_by:
- &id004
reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: EC=2.7.7.99
- &id005
reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: Reaction=N-acetyl-alpha-D-muramate 1-phosphate + UDP + H(+) = UDP-N-
- term:
id: GO:0070569
label: uridylyltransferase activity
evidence_type: IDA
original_reference_id: PMID:25767118
review:
summary: MurU directly catalyzes uridylyl transfer from UTP to MurNAc-alpha-1-phosphate, so this is the core molecular function.
action: ACCEPT
reason: The term captures the experimentally supported EC 2.7.7.99 activity.
supported_by:
- *id004
- *id005
- term:
id: GO:0097172
label: N-acetylmuramic acid metabolic process
evidence_type: IMP
original_reference_id: PMID:23831760
review:
summary: The enzyme directly metabolizes an N-acetylmuramic acid derivative in the recycling route.
action: ACCEPT
reason: MurU catalyzes conversion of MurNAc-alpha-1-phosphate to UDP-MurNAc.
supported_by:
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: Catalyzes the formation of UDP-N-acetylmuramate (UDP-MurNAc),
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: a crucial precursor of the bacterial peptidoglycan cell wall, from UTP
- term:
id: GO:0097367
label: carbohydrate derivative binding
evidence_type: IDA
original_reference_id: PMID:25767118
review:
summary: MurU binds carbohydrate-derived MurNAc-alpha-1-phosphate as substrate; the binding term is valid but less informative than the reaction term.
action: KEEP_AS_NON_CORE
reason: Retain as non-core substrate binding.
supported_by:
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: MurNAc-alpha-1P (PubMed:23831760, PubMed:25767118).
references:
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models.
findings:
- statement: ARBA supplies automated annotations that are useful but must be checked against direct gene evidence.
- id: file:PSEPK/murU/murU-uniprot.txt
title: UniProtKB reviewed entry for murU
findings:
- statement: UniProt identifies murU as MurNAc-alpha-1-phosphate uridylyltransferase with EC 2.7.7.99 and peptidoglycan-recycling pathway placement.
- id: GO_REF:0000041
title: Gene Ontology annotation based on UniPathway vocabulary mapping.
findings:
- statement: UniPathway mapping provides pathway annotations that should be retained only when the gene directly catalyzes or regulates that pathway step.
- id: PMID:25767118
title: Crystal Structure of the N-Acetylmuramic Acid α-1-Phosphate (MurNAc-α1-P) Uridylyltransferase MurU, a Minimal Sugar Nucleotidyltransferase and Potential Drug Target Enzyme in Gram-negative Pathogens.
findings:
- statement: MurU structure and biochemistry support UTP, MurNAc-alpha-1-phosphate, and magnesium-dependent uridylyltransferase activity.
- id: PMID:23831760
title: A cell wall recycling shortcut that bypasses peptidoglycan de novo biosynthesis.
findings:
- statement: A cell-wall recycling shortcut in P. putida uses AmgK and MurU to channel external MurNAc into peptidoglycan biosynthesis.
- id: file:PSEPK/murU/murU-deep-research-falcon.md
title: Falcon deep research on murU (Edison Scientific Literature)
findings:
- statement: MurU is the MurNAc salvage/recycling uridylyltransferase that generates UDP-MurNAc, acting downstream of the anomeric MurNAc kinase AmgK in P. putida KT2440 (PP_0406).
supporting_text: |-
The UniProt target Q88QT2 is annotated as **MurU (murU; PP_0406)**, an **N-acetylmuramate α-1-phosphate uridylyltransferase** (EC 2.7.7.99) belonging to the **nucleotidyltransferase/MurU family** (GlmU-like NTP transferase fold). In the retrieved literature corpus, “MurU” is consistently used for the **MurNAc (N-acetylmuramic acid) salvage/recycling uridylyltransferase** that generates UDP-MurNAc downstream of an anomeric MurNAc kinase (AmgK).
- statement: In vitro with the P. putida recycling enzymes, MurU acts after AmgK and converts MurNAc monophosphate intermediates into the corresponding UDP-MurNAc derivatives.
supporting_text: |-
Direct biochemical evidence in the retrieved corpus comes from work using the **P. putida cell-wall recycling enzymes AmgK and MurU** in vitro. In these experiments, MurU acts **after AmgK** (which generates a monophosphate MurNAc intermediate) and **converts MurNAc monophosphate intermediates into the corresponding UDP-sugars (UDP-MurNAc derivatives)**, as detected by high-resolution LC/MS.
- statement: MurU's product UDP-MurNAc is competent for entry into peptidoglycan precursor assembly, being accepted by downstream MurC-MurF ligases to make Park's nucleotide analogs.
supporting_text: |-
MurU’s product is functionally validated in the same experimental system because the resulting UDP-MurNAc derivatives were accepted by downstream **MurC–MurF** enzymes to generate Park’s nucleotide analogs, demonstrating that MurU’s product is competent for entry into PG precursor assembly.
- statement: MurU's physiological substrate is MurNAc-1P (generated by AmgK), though the enzyme tolerates several MurNAc substitutions, enabling bioorthogonal probe generation.
supporting_text: |-
**Interpretation for annotation:** MurU’s physiological substrate is MurNAc-1P (generated by AmgK from imported MurNAc/anhMurNAc-derived intermediates), but the enzyme exhibits practical tolerance for several substitutions on MurNAc, enabling probe generation.
- statement: The MurU salvage route provides an alternate path to UDP-MurNAc that bypasses the de novo MurA/MurB steps, relevant under fosfomycin-mediated MurA inhibition.
supporting_text: |-
The MurU salvage route is biologically important because it provides an **alternate route to UDP-MurNAc** that can **bypass dependence on the de novo MurA/MurB steps** under conditions where de novo synthesis is impaired (e.g., MurA inhibition by fosfomycin), a point emphasized in the labeling-and-rescue framework.
- statement: No direct localization experiment exists for P. putida MurU, but pathway context supports a cytosolic role generating the cytosolic precursor UDP-MurNAc for Mur ligases.
supporting_text: |-
However, pathway context strongly supports a **cytosolic localization**: Gram-negative PG fragments are described as being transported into the **cytoplasm** for recycling (e.g., via AmpG), and MurU generates **UDP-MurNAc**, which is a cytosolic precursor used by Mur ligases (MurC–MurF). Thus, MurU is best annotated as a **cytoplasmic enzyme** acting on MurNAc-phosphate intermediates arising from imported PG turnover products.
core_functions:
- description: MurU catalyzes UTP-dependent formation of UDP-MurNAc from MurNAc-alpha-1-phosphate in a peptidoglycan recycling shortcut, supplying a cell-wall precursor and contributing to bypass of de novo UDP-MurNAc biosynthesis.
molecular_function:
id: GO:0070569
label: uridylyltransferase activity
directly_involved_in:
- id: GO:0009254
label: peptidoglycan turnover
- id: GO:0097172
label: N-acetylmuramic acid metabolic process
supported_by:
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: Catalyzes the formation of UDP-N-acetylmuramate (UDP-MurNAc),
- reference_id: file:PSEPK/murU/murU-uniprot.txt
supporting_text: 'PATHWAY: Cell wall biogenesis; peptidoglycan recycling.'
- reference_id: PMID:23831760
supporting_text: The anomeric sugar kinase AmgK and the MurNAc α-1-phosphate uridylyl
- reference_id: file:PSEPK/murU/murU-deep-research-falcon.md
supporting_text: |-
**murU (Q88QT2; PP_0406) encodes a cytosolic N-acetylmuramate-α-1-phosphate uridylyltransferase (MurU; EC 2.7.7.99) that converts MurNAc-1-phosphate to UDP-MurNAc in the MurNAc salvage (MurU shunt) arm of peptidoglycan recycling, acting downstream of AmgK and upstream of MurC–MurF to regenerate PG precursors; the P. putida AmgK/MurU system shows experimentally demonstrated promiscuity toward several MurNAc analogs enabling metabolic labeling and probe generation.**
proposed_new_terms: []
suggested_questions:
- question: Under which environmental conditions does MurU-dependent MurNAc salvage materially contribute to peptidoglycan precursor supply or fosfomycin tolerance in KT2440?
experts:
- Bacterial cell-wall recycling experts
suggested_experiments:
- description: Compare wild type, murU deletion, and complemented strains for growth on exogenous MurNAc, UDP-MurNAc pool sizes, and fosfomycin sensitivity with and without MurNAc supplementation.
experiment_type: cell-wall precursor metabolomics and antibiotic sensitivity assay