GO:0061611 mannose to fructose-6-phosphate catabolic process: Metabolic Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0061611 describes the biochemical conversion of mannose to fructose-6-phosphate, a central entry point into glycolysis.
• The pathway hinges on mannose-6-phosphate isomerase (MPI), which reversibly converts mannose-6-phosphate to fructose-6-phosphate.
• MPI is a metal-dependent enzyme whose catalytic mechanism has been resolved by X-ray crystallography.
• Mannose metabolism intersects with viral replication, fungal pathogenesis, and cancer cell proteome remodeling.
• Quantitative methods such as HILIC-QqQ-MS/MS enable sensitive measurement of phosphorylated carbohydrate intermediates in this pathway.
• Engineered microbial systems exploit this pathway for biotechnological fructose-6-phosphate production.
Description
Mannose to fructose-6-phosphate catabolic process (GO:0061611) is a biological process defined as the chemical reactions and pathways in which mannose, the aldohexose manno-hexose, is converted to fructose-6-phosphate. This process is a critical metabolic route because fructose-6-phosphate is a key glycolytic intermediate, linking mannose utilization to central carbon metabolism and energy production. Understanding this pathway is essential for researchers studying carbohydrate metabolism, microbial physiology, and metabolic reprogramming in disease states. The pathway is initiated by the phosphorylation of mannose to mannose-6-phosphate, followed by isomerization to fructose-6-phosphate, a reaction catalyzed by mannose-6-phosphate isomerase (MPI). MPI is a metalloenzyme that requires divalent metal ions for activity, and its catalytic mechanism has been characterized in detail using structural biology approaches. In addition to its role in normal metabolism, this pathway has been implicated in diverse biological contexts, including viral replication, fungal pathogenicity, and cancer cell adaptation. For example, glucose and glutamine metabolism, which intersects with mannose catabolism, drives hepatitis E virus replication. In melanoma cells, the functional status of MPI shapes global proteome and degradome rearrangements, highlighting the broad impact of this pathway on cellular physiology. Furthermore, mannitol metabolism during fungal-host interactions under stressed conditions underscores the importance of mannose-related pathways in microbial pathogenesis. Biotechnologically, the conversion of mannose to fructose-6-phosphate is exploited for the production of fructose-6-phosphate, a valuable compound in the food and pharmaceutical industries. The transport of hexose phosphates across bacterial membranes, as characterized in Streptococcus lactis, further illustrates the diversity of systems that feed into or regulate this pathway. Given its central role in metabolism and its connections to disease and biotechnology, GO:0061611 is a focus of ongoing research, and precise experimental models are needed to dissect its regulation and function.
mannose to fructose-6-phosphate catabolic process At A Glance
| GO ID | GO:0061611 |
|---|---|
| GO term | mannose to fructose-6-phosphate catabolic process |
| Ontology | biological_process |
| Synonym | mannose metabolism to fructose-6-phosphate |
| Major function | Conversion of mannose to fructose-6-phosphate, linking mannose utilization to glycolysis |
| Key enzyme | Mannose-6-phosphate isomerase (MPI) |
| Cofactors | Divalent metal ions (e.g., Zn2+, Co2+) for MPI activity |
| Related pathways | Glycolysis, mannose metabolism, fructose and mannose degradation |
| Organisms | Bacteria, fungi, animals, including humans |
What Is GO:0061611?
GO:0061611, mannose to fructose-6-phosphate catabolic process, is defined as the chemical reactions and pathways in which mannose, the aldohexose manno-hexose, is converted to fructose-6-phosphate. This process encompasses the enzymatic steps that transform mannose into fructose-6-phosphate, a key intermediate in glycolysis. The pathway typically involves the phosphorylation of mannose to mannose-6-phosphate and its subsequent isomerization to fructose-6-phosphate, catalyzed by mannose-6-phosphate isomerase.
Why Is mannose to fructose-6-phosphate catabolic process Important in Cell Biology?
The mannose to fructose-6-phosphate catabolic process is fundamentally important because it connects mannose, a hexose sugar, to the glycolytic pathway via fructose-6-phosphate, thereby influencing cellular energy production and biosynthetic precursors. This pathway is conserved across bacteria, fungi, and animals, and its dysregulation has been linked to viral replication, fungal pathogenesis, and cancer cell metabolism. In hepatitis E virus infection, glucose and glutamine metabolism, which intersects with mannose catabolism, is required for efficient viral replication. In melanoma, the functional status of mannose-6-phosphate isomerase (MPI) drives proteome and degradome rearrangements, suggesting a role in tumor cell adaptation. Moreover, the pathway is exploited biotechnologically for fructose-6-phosphate production, a compound with applications in food and pharmaceuticals. Thus, understanding GO:0061611 provides insights into basic metabolism, disease mechanisms, and biotechnological innovation.
• Provides a route for mannose to enter glycolysis, influencing energy production and metabolic flux.
• Mannose-6-phosphate isomerase (MPI) is a metal-dependent enzyme with a well-characterized catalytic mechanism.
• The pathway is implicated in viral replication, as glucose and glutamine metabolism supports hepatitis E virus replication.
• MPI functional status shapes proteome and degradome remodeling in melanoma cells, linking the pathway to cancer biology.
• Mannitol metabolism, which intersects with mannose pathways, is important during fungal-host interactions under stress.
• The pathway is targeted for biotechnological production of fructose-6-phosphate.
• Phosphate:hexose 6-phosphate antiport systems in bacteria regulate hexose phosphate transport, affecting mannose metabolism.
• Quantitative methods like HILIC-QqQ-MS/MS allow sensitive detection of phosphorylated carbohydrates in this pathway.
• The process is conserved across species, making it a model for studying enzyme evolution and metabolic regulation.
• Understanding this pathway can inform strategies for metabolic engineering and therapeutic intervention.
What Happens During mannose to fructose-6-phosphate catabolic process?
Uptake and Phosphorylation of Mannose
In simple terms: Mannose enters the cell and gets a phosphate group attached, becoming mannose-6-phosphate.
The first step in the mannose to fructose-6-phosphate catabolic process is the transport of mannose into the cell, followed by its phosphorylation to mannose-6-phosphate. This phosphorylation is typically catalyzed by hexokinase, which transfers a phosphate group from ATP to mannose. In bacteria, phosphate:hexose 6-phosphate antiport systems can also transport mannose-6-phosphate directly. The resulting mannose-6-phosphate is the substrate for the subsequent isomerization step.
Isomerization by Mannose-6-Phosphate Isomerase (MPI)
In simple terms: An enzyme called MPI rearranges mannose-6-phosphate into fructose-6-phosphate.
Mannose-6-phosphate isomerase (MPI) catalyzes the reversible isomerization of mannose-6-phosphate to fructose-6-phosphate. This reaction involves the opening of the sugar ring and isomerization via an enediol intermediate. Structural studies of MPI from Salmonella typhimurium bound to metal atoms and substrate have elucidated the catalytic mechanism, revealing the importance of divalent metal ions for activity. MPI is highly conserved and its function is critical for directing mannose into glycolysis.
Metal Dependence and Catalytic Mechanism
In simple terms: MPI needs metal ions to work, and its detailed mechanism has been solved.
MPI is a metalloenzyme that requires divalent metal ions, such as Zn2+ or Co2+, for catalytic activity. The crystal structure of MPI from Salmonella typhimurium in complex with metal atoms and substrate has provided insights into the catalytic mechanism, including the role of specific residues in substrate binding and catalysis. This metal dependence is a key feature of the enzyme and has implications for its regulation and inhibition.
Fate of Fructose-6-Phosphate
In simple terms: Fructose-6-phosphate then continues into glycolysis to make energy.
Fructose-6-phosphate produced by MPI enters the glycolytic pathway, where it is further metabolized to generate ATP and biosynthetic precursors. This links mannose catabolism to central carbon metabolism. In biotechnological applications, fructose-6-phosphate can be produced from mannose using MPI, as demonstrated in engineered microbial systems.
Regulation and Integration with Other Pathways
In simple terms: This pathway is controlled and connected to other metabolic routes.
The mannose to fructose-6-phosphate catabolic process is regulated at multiple levels, including enzyme expression and activity. MPI activity can be influenced by metal availability and post-translational modifications. The pathway intersects with other metabolic routes, such as mannitol metabolism in fungi and glucose/glutamine metabolism in viral infection. In melanoma cells, MPI functional status affects global proteome and degradome dynamics, indicating broader regulatory roles.
Key Genes Involved in GO:0061611 mannose to fructose-6-phosphate catabolic process
The following genes and proteins are directly involved in or closely associated with the mannose to fructose-6-phosphate catabolic process, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| MPI (mannose-6-phosphate isomerase) | Catalyzes isomerization of mannose-6-phosphate to fructose-6-phosphate | Target for metabolic engineering and cancer studies |
| HK (hexokinase) | Phosphorylates mannose to mannose-6-phosphate | Upstream regulator of mannose entry into glycolysis |
| PMI (phosphomannose isomerase) | Bacterial homolog of MPI, converts mannose-6-phosphate to fructose-6-phosphate | Biotechnological production of fructose-6-phosphate |
| manA (mannose-6-phosphate isomerase) | Bacterial gene encoding MPI | Model for enzyme structure-function studies |
| manB (phosphomannomutase) | Converts mannose-6-phosphate to mannose-1-phosphate | Linked to mannan synthesis in fungi |
| GFPT1 (glutamine--fructose-6-phosphate transaminase 1) | Uses fructose-6-phosphate for hexosamine biosynthesis | Connects to glutamine metabolism and viral replication |
| SLC2A (GLUT transporters) | Facilitate mannose uptake | Influence substrate availability for the pathway |
| PTS system (phosphotransferase system) | Bacterial mannose uptake and phosphorylation | Target for antibacterial strategies |
| MPI (Salmonella typhimurium) | Model enzyme for structural studies | Provides mechanistic insights into catalysis |
| MPI (Bacillus amyloliquefaciens) | Thermostable MPI for industrial applications | Used in fructose-6-phosphate production |
| MPI (human) | Central enzyme in mannose metabolism | Implicated in melanoma proteome remodeling |
| MPI (yeast) | Homolog involved in mannose utilization | Model for fungal metabolism |
| MPI (plant) | Role in ascorbate and cell wall synthesis | Potential for crop improvement |
| MPI (parasite) | Essential for mannose metabolism in pathogens | Drug target in parasitic infections |
| MPI (archaea) | Adapted to extreme environments | Biocatalyst for industrial processes |
| MPI (fungal) | Contributes to mannitol metabolism | Pathogenesis and stress response |
How Is mannose to fructose-6-phosphate catabolic process Regulated?
The mannose to fructose-6-phosphate catabolic process is regulated primarily through the expression and activity of mannose-6-phosphate isomerase (MPI). MPI activity is dependent on divalent metal ions, and its catalytic mechanism is finely tuned by specific amino acid residues. In melanoma cells, the functional status of MPI influences global proteome and degradome rearrangements, suggesting that MPI levels or activity can modulate broader cellular processes. Additionally, the pathway is integrated with glucose and glutamine metabolism, as seen in hepatitis E virus replication where these nutrients drive viral replication. In fungi, mannitol metabolism, which intersects with mannose pathways, is regulated during host interactions under stressed conditions. Transport of hexose phosphates via antiport systems can also affect substrate availability for MPI. Thus, regulation occurs at multiple levels, including enzyme abundance, metal cofactor availability, and metabolic cross-talk.
mannose to fructose-6-phosphate catabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| MPI | Melanoma proteome remodeling | MPI knockout melanoma cell lines |
| MPI | Hepatitis E virus replication | MPI overexpression in hepatoma cells |
| MPI | Fungal pathogenesis | Fungal MPI deletion strains |
| HK | Cancer metabolism | Hexokinase knockdown cancer cells |
| GFPT1 | Viral replication | GFPT1 knockout cells |
Cancer Metabolism and Melanoma
In melanoma cells, mannose-6-phosphate isomerase (MPI) functional status shapes a rearrangement in the proteome and degradome of mannose-treated cells, indicating that this pathway can influence tumor cell behavior and protein turnover. This suggests that MPI and the mannose to fructose-6-phosphate catabolic process may play a role in cancer metabolic reprogramming, potentially affecting cell survival and proliferation.
Viral Replication and Hepatitis E Virus
Glucose and glutamine metabolism drive hepatitis E virus replication, and this metabolic dependency intersects with mannose catabolism through fructose-6-phosphate, a key glycolytic intermediate. Therefore, the mannose to fructose-6-phosphate catabolic process may contribute to the metabolic environment that supports viral replication, making it a potential target for antiviral strategies.
Fungal Pathogenesis and Host Interactions
Mannitol metabolism during pathogenic fungal-host interactions under stressed conditions involves mannose-related pathways, including the conversion of mannose to fructose-6-phosphate. This pathway is important for fungal survival and virulence, and its manipulation could affect the outcome of fungal infections.
From mannose to fructose-6-phosphate catabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the effect of MPI loss on glycolysis? | MPI knockout cell line (e.g., CRISPR-Cas9) |
| How does MPI mutation affect enzyme activity? | Point mutation knock-in of catalytic residues |
| Can MPI be tagged for localization studies? | Knock-in of fluorescent tag at MPI locus |
| Does MPI overexpression alter proteome? | MPI overexpression in melanoma cells |
| What is the role of MPI in viral replication? | MPI knockout in hepatitis E virus-infected cells |
| How does MPI contribute to fungal virulence? | Fungal MPI deletion mutants |
How to Study the mannose to fructose-6-phosphate catabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| HILIC-QqQ-MS/MS | Quantification of phosphorylated carbohydrates | Metabolic profiling of mannose pathway |
| Proteomics | Global protein abundance changes | Assessing MPI-dependent proteome remodeling |
| Degradome analysis | Protein degradation rates | Identifying MPI-regulated degradation targets |
| X-ray crystallography | Three-dimensional enzyme structure | Elucidating MPI catalytic mechanism |
| Enzyme kinetics | Catalytic activity and substrate specificity | Characterizing MPI metal dependence |
| CRISPR-Cas9 knockout | Gene function loss | Studying MPI role in cells |
| Overexpression | Gain-of-function effects | Investigating MPI impact on proteome |
| Metabolic engineering | Production of fructose-6-phosphate | Biotechnological applications |
Quantitative Metabolomics for Phosphorylated Carbohydrates
HILIC-QqQ-MS/MS is a sensitive method for quantifying low-abundant phosphorylated carbohydrates, including mannose-6-phosphate and fructose-6-phosphate, enabling precise measurement of pathway flux. This approach is essential for studying the mannose to fructose-6-phosphate catabolic process in various biological samples.
Proteomics and Degradome Analysis
Proteomic and degradome analyses can reveal global changes in protein abundance and turnover upon modulation of MPI, as demonstrated in melanoma cells treated with mannose. These methods help uncover downstream effects of the pathway on cellular physiology.
Structural Biology and Enzyme Kinetics
X-ray crystallography of MPI bound to metal atoms and substrate has elucidated the catalytic mechanism, while enzyme kinetics provide insights into substrate specificity and metal dependence. Such studies are fundamental for understanding the molecular details of the pathway.
Microbial Genetics and Metabolic Engineering
Characterization of MPI from Bacillus amyloliquefaciens and its application in fructose-6-phosphate production demonstrates the use of microbial genetics and metabolic engineering to exploit this pathway. Additionally, phosphate:hexose 6-phosphate antiport studies in Streptococcus lactis inform transport mechanisms.
How CRISPR Can Be Used to Study GO:0061611 mannose to fructose-6-phosphate catabolic process
Knockout
CRISPR-Cas9 knockout of MPI can be used to abolish the mannose to fructose-6-phosphate catabolic process, allowing researchers to study its contribution to glycolysis, cell growth, and disease models such as melanoma. Knockout cell lines provide a clean background to test pathway-specific hypotheses.
Point Mutation
Introducing point mutations in MPI catalytic residues via CRISPR can help dissect the enzyme's mechanism and metal dependence, as informed by structural studies. Such models are valuable for understanding how specific amino acids contribute to catalysis.
Knock-in
Knock-in of epitope tags or fluorescent proteins at the endogenous MPI locus enables real-time tracking of MPI expression and localization without altering its regulation. This approach is useful for studying MPI dynamics in live cells.
Overexpression
CRISPR-mediated overexpression of MPI can be achieved by inserting a strong promoter, allowing researchers to investigate gain-of-function effects on the proteome and degradome, as seen in melanoma cells. Overexpression models help identify downstream pathways affected by enhanced mannose catabolism.
How EDITGENE Supports mannose to fructose-6-phosphate catabolic process Research
Researchers studying mannose to fructose-6-phosphate catabolic process-related genes often need to determine whether a candidate gene is causally involved in metabolic regulation, disease progression, or biotechnological production. EDITGENE provides comprehensive CRISPR-based services to create precise cellular models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for mannose to fructose-6-phosphate catabolic process research.
Frequently Asked Questions About mannose to fructose-6-phosphate catabolic process
What is GO:0061611?
GO:0061611 is the Gene Ontology term for mannose to fructose-6-phosphate catabolic process, defined as the chemical reactions and pathways in which mannose is converted to fructose-6-phosphate.
What genes are involved in mannose to fructose-6-phosphate catabolic process?
Key genes include MPI (mannose-6-phosphate isomerase), which catalyzes the isomerization step, and hexokinase, which phosphorylates mannose.
What is the role of mannose-6-phosphate isomerase (MPI)?
MPI catalyzes the reversible conversion of mannose-6-phosphate to fructose-6-phosphate, a critical step in mannose catabolism.
How is mannose to fructose-6-phosphate catabolic process regulated?
It is regulated by MPI expression and activity, metal ion availability, and integration with other metabolic pathways such as glycolysis and glutamine metabolism.
What diseases are associated with mannose to fructose-6-phosphate catabolic process?
It has been implicated in melanoma proteome remodeling, hepatitis E virus replication, and fungal pathogenesis.
What methods are used to study mannose to fructose-6-phosphate catabolic process?
Methods include HILIC-QqQ-MS/MS for metabolite quantification, proteomics, X-ray crystallography, and CRISPR-based gene editing.
Can CRISPR be used to study mannose to fructose-6-phosphate catabolic process?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models can be used to dissect the pathway's function.
What is the connection between mannose metabolism and cancer?
MPI functional status shapes proteome and degradome rearrangements in melanoma cells, suggesting a role in cancer metabolism.
How does mannose metabolism affect viral replication?
Glucose and glutamine metabolism, which intersects with mannose catabolism, drives hepatitis E virus replication.
What is the biotechnological application of mannose to fructose-6-phosphate catabolic process?
It is used for the production of fructose-6-phosphate, a valuable compound in food and pharmaceutical industries.
Conclusion
The mannose to fructose-6-phosphate catabolic process (GO:0061611) is a fundamental metabolic pathway that links mannose utilization to glycolysis via fructose-6-phosphate. Its central enzyme, MPI, is a metal-dependent isomerase with a well-characterized catalytic mechanism. The pathway has broad implications in cancer, viral infection, and fungal pathogenesis, and is exploited in biotechnology for fructose-6-phosphate production. Researchers can leverage CRISPR-based models and advanced analytical methods to further dissect its regulation and roles in health and disease.
References
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- 2. Sigdel S et al.. 2015. Characterization of a Mannose-6-Phosphate Isomerase from Bacillus amyloliquefaciens and Its Application in Fructose-6-Phosphate Production.. PLoS One 10(7):e0131585 PMID: 26171785
- 3. Sagurthi SR et al.. 2009. Structures of mannose-6-phosphate isomerase from Salmonella typhimurium bound to metal atoms and substrate: implications for catalytic mechanism.. Acta Crystallogr D Biol Crystallogr 65(Pt 7):724-32 PMID: 19564693
- 4. Khan S et al.. 2024. Glucose and glutamine drive hepatitis E virus replication.. Arch Virol 169(11):233 PMID: 39476184
- 5. Jorge TF et al.. 2018. Quantification of Low-Abundant Phosphorylated Carbohydrates Using HILIC-QqQ-MS/MS.. Methods Mol Biol 1778:71-86 PMID: 29761432
- 6. Meena M et al.. 2015. Mannitol metabolism during pathogenic fungal-host interactions under stressed conditions.. Front Microbiol 6:1019 PMID: 26441941
- 7. Wang Y et al.. 2024. Biosynthesis of mannose from glucose via constructing phosphorylation-dephosphorylation reactions in Escherichia coli.. Enzyme Microb Technol 177:110427 PMID: 38518553
- 8. Ambudkar SV et al.. 1984. Characterization of phosphate:hexose 6-phosphate antiport in membrane vesicles of Streptococcus lactis.. J Biol Chem 259(20):12576-85 PMID: 6436237
