GO:0005991 trehalose metabolic process: Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0005991 trehalose metabolic process describes the chemical reactions and pathways involving trehalose, a disaccharide of two glucose molecules isomeric with sucrose.
• Trehalose metabolism is best understood in bacteria, fungi, plants and invertebrates, while vertebrates generally lack the ability to synthesize trehalose.
• In mycobacteria, trehalose metabolism is genetically tractable and produces immunologically important glycolipids such as trehalose dimycolate.
• In yeast, trehalose and its precursor trehalose 6-phosphate act as stress protectants and regulators of glycolysis and growth.
• In plants, trehalose 6-phosphate is a signaling metabolite that influences development, carbon allocation and yield in C3 and C4 species.
• Experimental study of trehalose metabolic process relies on genetic knockouts, enzyme assays, metabolomics and heterologous expression of trehalose synthases.
Description
Trehalose metabolic process (GO:0005991) is the biological process comprising the chemical reactions and pathways that build, modify and break down trehalose, a non-reducing disaccharide composed of two glucose units that is isomeric with sucrose. The term is a biological_process ontology node and is used to annotate gene products that catalyze or regulate trehalose synthesis, interconversion and degradation across taxa. Because trehalose is a stable, osmotically inert molecule, its metabolism is tightly linked to stress survival, carbon storage and signaling in many organisms. In bacteria, trehalose metabolism is not only a carbon-handling pathway but also a source of cell-wall and virulence-associated glycolipids, making it a genetically and pharmacologically interesting system. In fungi such as Saccharomyces cerevisiae, trehalose and its phosphorylated intermediate trehalose 6-phosphate are central to heat, osmotic and oxidative stress tolerance, and they also modulate glycolytic flux. In plants, trehalose 6-phosphate metabolism has emerged as a regulatory hub that coordinates sucrose availability with growth and development, including in C4 crops. Vertebrates, by contrast, appear to have lost the capacity for de novo trehalose synthesis, which raises comparative and evolutionary questions about why the pathway is retained in so many other lineages. For researchers, GO:0005991 provides a precise annotation target for functional genomics, microbial pathogenesis, plant physiology and metabolic engineering studies.
trehalose metabolic process At A Glance
| GO ID | GO:0005991 |
|---|---|
| GO term | trehalose metabolic process |
| Ontology | biological_process |
| Synonym | mycose metabolic process; mycose metabolism; mykose metabolic process; mykose metabolism; trehalose metabolism |
| Major function | Synthesis, interconversion and degradation of the disaccharide trehalose and its phosphorylated intermediate trehalose 6-phosphate |
| Taxonomic scope | Bacteria, fungi, plants, invertebrates and some other eukaryotes; vertebrates generally cannot synthesize trehalose |
| Key intermediate | Trehalose 6-phosphate, a precursor and signaling metabolite |
| Representative enzymes | Trehalose synthase, trehalose 6-phosphate synthase, trehalose 6-phosphate phosphatase and trehalase |
| Disease relevance | Mycobacterial pathogenesis, fungal stress adaptation and plant stress/yield traits |
What Is GO:0005991?
In plain terms, GO:0005991 trehalose metabolic process is the set of biochemical reactions and pathways that make, convert and consume trehalose, a two-glucose sugar that is isomeric with sucrose. The QuickGO definition emphasizes the chemical reactions and pathways involving trehalose, and the term carries synonyms such as mycose metabolic process, mycose metabolism, mykose metabolic process, mykose metabolism and trehalose metabolism. It is a biological_process term, meaning it describes a coordinated series of molecular events rather than a single molecular function or cellular location. Annotations under this term can include enzymes that synthesize trehalose from glucose donors, enzymes that interconvert trehalose and trehalose 6-phosphate, and enzymes that hydrolyze trehalose into glucose. Because the same metabolite can be produced by different routes in different organisms, the term is intentionally broad and is often used together with more specific child terms in functional annotation.
Why Is trehalose metabolic process Important in Cell Biology?
Trehalose metabolic process matters because trehalose is a chemically robust sugar that organisms use to survive desiccation, heat, cold and oxidative stress, and because its phosphorylated intermediate trehalose 6-phosphate acts as a signaling molecule in plants and fungi. In mycobacteria, trehalose metabolism generates glycolipids that are central to cell envelope structure and host immune recognition, which makes the pathway a target for tuberculosis research. In yeast, trehalose accumulation correlates with stress resistance and chronological longevity, and the pathway is a model for understanding how metabolism is rewired under stress. In plants, trehalose 6-phosphate metabolism influences sucrose utilization, development and yield, including in C4 species of agronomic importance. In biotechnology, trehalose metabolism is exploited for industrial trehalose production using recombinant trehalose synthase. Finally, the apparent absence of trehalose synthesis in vertebrates makes the pathway a comparative model for understanding metabolic pathway loss and host-microbe interactions.
• Provides a genetic and biochemical framework for mycobacterial cell envelope and virulence studies.
• Underpins stress tolerance and longevity phenotypes in yeast and other fungi.
• Acts as a signaling hub linking sucrose status to growth in plants, including C4 crops.
• Enables industrial-scale trehalose production through recombinant trehalose synthase.
• Explains why many invertebrates and microbes survive desiccation and extreme temperatures.
• Highlights an evolutionary puzzle because vertebrates generally cannot synthesize trehalose.
• Offers targets for anti-mycobacterial and anti-fungal strategies.
• Supports metabolic engineering of carbon flux in bacteria and plants.
• Serves as a model pathway for studying metabolite signaling by trehalose 6-phosphate.
• Connects to human health through host-microbe interactions and immunomodulatory glycolipids.
What Happens During trehalose metabolic process?
Synthesis of trehalose from glucose donors
In simple terms: Cells build trehalose by joining two glucose molecules together using specialized enzymes.
The best-characterized route to trehalose is the two-step pathway in which trehalose 6-phosphate synthase transfers glucose from a donor such as UDP-glucose or ADP-glucose to glucose 6-phosphate, forming trehalose 6-phosphate, which is then dephosphorylated by trehalose 6-phosphate phosphatase to yield free trehalose. In bacteria, alternative routes exist, including trehalose synthase, which can convert maltose to trehalose in a single reversible reaction, and this enzyme has been used for recombinant trehalose production. The diversity of synthetic routes means that annotation to GO:0005991 can reflect different enzyme architectures depending on the organism.
Interconversion and salvage of trehalose 6-phosphate
In simple terms: Trehalose 6-phosphate is a middleman that can be made, broken down or used as a signal.
Trehalose 6-phosphate sits at the crossroads of trehalose metabolism and is both a biosynthetic intermediate and a regulatory metabolite. In plants, trehalose 6-phosphate levels are sensed by downstream effectors and influence sucrose allocation, development and yield, which is why the metabolite is studied as a signal rather than only as a precursor. In yeast, trehalose 6-phosphate is rapidly turned over in response to stress and nutrient signals, and its balance with trehalose is thought to influence glycolytic flux and growth. Because the same metabolite can be produced and consumed by multiple enzymes, its steady-state level is a sensitive readout of pathway activity.
Degradation of trehalose by trehalases
In simple terms: When cells need glucose, trehalose is cut back into two glucose molecules.
Trehalose is hydrolyzed to glucose by trehalases, which are found in bacteria, fungi, plants and invertebrates and are often regulated in response to nutrient and stress conditions. In yeast, trehalase activity is controlled by post-translational modification and by the availability of trehalose, allowing rapid mobilization of glucose when energy is needed. In bacteria, trehalose can also be consumed through catabolic pathways that feed glucose into central carbon metabolism, and the balance between synthesis and degradation determines whether trehalose accumulates as a protectant or is used as a carbon source. This degradative arm is essential for the dynamic nature of GO:0005991 and for its role in stress recovery.
Trehalose-containing glycolipids in mycobacteria
In simple terms: Some bacteria decorate their surface with sugars built from trehalose.
In mycobacteria, trehalose metabolism supplies the disaccharide core for glycolipids such as trehalose dimycolate and trehalose monomycolate, which are abundant in the cell envelope and interact with host immune receptors. Genetic studies in Mycobacterium species have defined enzymes that synthesize, modify and export these trehalose-containing lipids, linking GO:0005991 to cell wall integrity and virulence. Because these glycolipids are important for pathogenesis, the pathway is a focus for anti-mycobacterial target discovery.
Stress-responsive accumulation and protection
In simple terms: Many organisms stockpile trehalose to survive harsh conditions.
Trehalose accumulates to high levels in many fungi, plants and invertebrates during heat, cold, osmotic or oxidative stress, where it stabilizes proteins and membranes. In yeast, trehalose accumulation is a hallmark of stationary phase and stress resistance, and mutants with altered trehalose metabolism show changed survival under stress. In plants, trehalose 6-phosphate metabolism is integrated with stress and developmental signaling, and manipulation of pathway genes can alter stress tolerance and growth. These protective roles explain why GO:0005991 is frequently studied in environmental and agricultural contexts.
Evolutionary distribution and pathway loss
In simple terms: Some animals, including vertebrates, seem to have lost the ability to make trehalose.
Comparative analyses indicate that vertebrates generally cannot synthesize trehalose, although they can digest dietary trehalose using trehalase. This distribution suggests that the pathway has been retained in lineages where trehalose provides a selective advantage, such as microbes, plants and invertebrates, and lost where it is dispensable. The evolutionary pattern makes GO:0005991 a useful case study for understanding metabolic pathway gain, loss and host-microbe dependence.
Key Genes Involved in GO:0005991 trehalose metabolic process
The following genes and gene products are representative of trehalose metabolic process across bacteria, fungi and plants, based on the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| otsA | Trehalose 6-phosphate synthase in bacteria | Bacterial trehalose synthesis and stress studies |
| otsB | Trehalose 6-phosphate phosphatase in bacteria | Dephosphorylation step of trehalose synthesis |
| treS | Trehalose synthase converting maltose to trehalose | Recombinant trehalose production and pathway engineering |
| treY | Maltooligosyltrehalose synthase | Alternative bacterial trehalose route |
| treZ | Maltooligosyltrehalose trehalohydrolase | Alternative bacterial trehalose route |
| treA | Periplasmic trehalase | Trehalose degradation and carbon utilization |
| TPS1 | Trehalose 6-phosphate synthase in yeast and plants | Core synthetic enzyme and stress signaling |
| TPS2 | Trehalose 6-phosphate phosphatase in yeast and plants | Produces free trehalose and influences signaling |
| TSL1 | Regulatory subunit of trehalose synthase complex in yeast | Complex assembly and stress response |
| NTH1 | Neutral trehalase in yeast | Trehalose mobilization and stress recovery |
| ATH1 | Acid trehalase in yeast | Vacuolar trehalose catabolism |
| TREH | Human trehalase | Dietary trehalose digestion in vertebrates |
| TPP | Trehalose 6-phosphate phosphatase family in plants | Trehalose 6-phosphate signaling and growth |
| T6P | Trehalose 6-phosphate metabolite node | Signaling of sucrose status in plants |
| PEPCK | Gluconeogenic enzyme linked to trehalose metabolism in some systems | Carbon flux integration |
| HXK2 | Hexokinase influencing trehalose metabolism in yeast | Glycolytic crosstalk |
| G6PDH | Glucose-6-phosphate dehydrogenase linked to trehalose pathway flux | Redox and carbon partitioning |
How Is trehalose metabolic process Regulated?
Trehalose metabolic process is regulated at multiple levels. In yeast, trehalose synthesis is induced by stress and nutrient limitation, and the activity of the trehalose synthase complex is controlled by regulatory subunits and post-translational modification. In plants, trehalose 6-phosphate levels are tightly regulated and act as a signal that coordinates sucrose availability with growth, partly through effects on gene expression and enzyme activity. In bacteria, trehalose metabolism is regulated in response to osmotic stress and carbon source availability, and the pathway can be switched between synthesis and degradation depending on environmental conditions. In mycobacteria, the pathway is integrated with cell envelope biosynthesis and virulence gene regulation. These regulatory layers ensure that trehalose and trehalose 6-phosphate levels are matched to cellular needs.
trehalose metabolic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| otsA/otsB | Mycobacterial cell envelope and virulence | Mycobacterium knockout and complementation |
| treS | Bacterial trehalose synthesis and industrial production | Recombinant E. coli expression |
| TPS1/TPS2 | Fungal stress tolerance and virulence | Yeast deletion and stress assays |
| TREH | Dietary trehalose digestion in vertebrates | Mammalian cell or animal knockout |
| TPP/T6P | Plant development and yield | Plant knockout and overexpression lines |
Mycobacterial pathogenesis and tuberculosis
Trehalose metabolism in Mycobacterium tuberculosis and related species produces glycolipids that are important for cell envelope integrity and host immune modulation, making the pathway relevant to tuberculosis pathogenesis and drug discovery. Genetic disruption of trehalose metabolic genes can alter bacterial growth and host interactions, which is why these genes are studied as potential targets.
Fungal stress adaptation and opportunistic infection
In pathogenic fungi, trehalose accumulation contributes to stress survival and virulence, and the pathway is linked to the ability to withstand host defenses. Understanding trehalose metabolism in fungi can inform antifungal strategies and help explain why some fungi persist in hostile environments.
Plant stress, development and yield
In plants, trehalose 6-phosphate metabolism is associated with stress responses, developmental transitions and yield traits, including in C4 crops. Manipulating pathway genes can change carbon allocation and stress tolerance, which has implications for agriculture and food security.
Vertebrate metabolism and host-microbe interactions
Vertebrates generally cannot synthesize trehalose but can digest it using trehalase, so trehalose metabolism in the host is largely about dietary handling and interactions with trehalose-producing microbes. This makes the pathway relevant to understanding host-microbe metabolic exchange and to interpreting the effects of dietary trehalose.
From trehalose metabolic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a trehalose synthesis gene reduce stress survival? | Knockout in yeast or bacteria |
| Does a point mutation alter enzyme activity? | Point-mutation knock-in in a model organism |
| Can a tagged enzyme be localized in cells? | Tagged knock-in of the endogenous locus |
| Does overexpression increase trehalose accumulation? | Overexpression of synthase or phosphatase |
| Which genes are required for trehalose-dependent virulence? | CRISPR library screening in bacteria |
| How does trehalose 6-phosphate signaling affect plant growth? | Plant knockout and overexpression lines |
How to Study the trehalose metabolic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Gene knockout | Loss-of-function phenotype | Testing requirement of a trehalose gene |
| Overexpression | Gain-of-function and metabolite accumulation | Increasing trehalose production |
| Enzyme assay | Catalytic activity and kinetics | Characterizing synthase or phosphatase |
| Metabolomics | Trehalose and trehalose 6-phosphate levels | Pathway flux and signaling |
| Transcriptomics | Expression of pathway genes | Stress and developmental responses |
| Proteomics | Protein abundance and modifications | Regulation of pathway enzymes |
| Imaging | Localization of tagged enzymes | Subcellular pathway organization |
| CRISPR library screening | Genes required for a phenotype | Identifying pathway dependencies |
Genetic perturbation and phenotypic assays
Knockout, knockdown and overexpression of trehalose metabolic genes are used to test causality, followed by growth, stress survival and metabolite measurements. In bacteria, allelic exchange and CRISPR-based editing enable precise deletion of synthesis or degradation genes. In yeast, deletion collections and inducible promoters allow controlled pathway manipulation.
Metabolite quantification
Trehalose and trehalose 6-phosphate levels are measured by enzymatic assays, chromatography or mass spectrometry to determine pathway activity and flux. In plants, trehalose 6-phosphate quantification is central to linking the metabolite to signaling and growth phenotypes. In industrial settings, trehalose yield is measured to optimize recombinant production.
Enzyme activity and biochemical reconstitution
Recombinant enzymes such as trehalose synthase, trehalose 6-phosphate synthase and trehalose 6-phosphate phosphatase are purified and assayed to define substrate specificity, kinetics and regulation. These assays help assign enzyme function to GO:0005991 and distinguish between synthetic and degradative routes.
Omics and systems-level analysis
Transcriptomics, proteomics and metabolomics are used to profile pathway gene expression and metabolite changes under stress or developmental transitions. In mycobacteria, systems-level studies link trehalose metabolism to cell envelope gene networks. In plants, omics approaches reveal how trehalose 6-phosphate signaling integrates with carbon metabolism.
How CRISPR Can Be Used to Study GO:0005991 trehalose metabolic process
Knockout
CRISPR knockout of trehalose metabolic genes is used to test whether a candidate gene is required for trehalose synthesis, stress survival or virulence. In bacteria, knockout of otsA, otsB or treS can reduce trehalose levels and alter phenotypes, while in yeast deletion of TPS1 or TPS2 affects stress tolerance. These models provide causal evidence linking a gene to GO:0005991.
Point Mutation
CRISPR point mutation can introduce catalytic-dead or regulatory mutations into trehalose enzymes to separate enzymatic activity from other functions. For example, mutating active-site residues of trehalose synthase can reveal which residues are essential for catalysis. Such models are useful when a complete knockout is lethal or when subtle activity changes are being studied.
Knock-in
Knock-in of tags or reporters at endogenous trehalose metabolic loci allows real-time tracking of protein localization and abundance. Tagged knock-in of trehalose enzymes can show whether they localize to specific compartments or complexes. Knock-in of disease-relevant alleles can also model human trehalase variation.
Overexpression
CRISPR activation or transgenic overexpression of trehalose synthesis genes increases trehalose accumulation and can enhance stress tolerance. In biotechnology, overexpression of trehalose synthase in recombinant hosts is used for trehalose production. In plants, overexpression of trehalose 6-phosphate pathway genes can alter growth and carbon allocation.
How EDITGENE Supports trehalose metabolic process Research
Researchers studying trehalose metabolic process-related genes often need to determine whether a candidate gene is causally involved in trehalose synthesis, degradation or signaling, and whether its manipulation changes stress survival, metabolite levels or host interactions. EDITGENE provides the CRISPR and cell-model tools needed to move from correlation to causation in bacterial, fungal, plant and mammalian systems.
Contact EDITGENE today to design your custom CRISPR model for trehalose metabolic process research.
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Frequently Asked Questions About trehalose metabolic process
What is trehalose metabolic process?
Trehalose metabolic process (GO:0005991) is the set of biochemical reactions and pathways that synthesize, interconvert and degrade trehalose, a disaccharide of two glucose molecules isomeric with sucrose.
What genes are involved in trehalose metabolic process?
Representative genes include otsA, otsB, treS, treY, treZ and treA in bacteria, TPS1, TPS2, TSL1, NTH1 and ATH1 in yeast, TPS1 and TPP in plants, and TREH in vertebrates.
Why is trehalose important for stress survival?
Trehalose stabilizes proteins and membranes during heat, cold, osmotic and oxidative stress, and its accumulation correlates with stress resistance in many organisms.
Do humans synthesize trehalose?
Vertebrates generally cannot synthesize trehalose, although they can digest dietary trehalose using trehalase.
What is trehalose 6-phosphate?
Trehalose 6-phosphate is the phosphorylated precursor of trehalose and also acts as a signaling metabolite, especially in plants and yeast.
How is trehalose made in bacteria?
Bacteria can make trehalose through the OtsA/OtsB pathway, through TreS-mediated conversion of maltose, or through TreY/TreZ routes.
Why is trehalose metabolism important in tuberculosis?
In mycobacteria, trehalose metabolism produces glycolipids that are important for cell envelope integrity and host immune interactions, making the pathway relevant to tuberculosis research.
How do researchers study trehalose metabolic process?
Researchers use gene knockouts, overexpression, enzyme assays, metabolomics, transcriptomics and CRISPR screening to study the pathway.
Can CRISPR be used to study trehalose metabolism?
Yes, CRISPR knockout, point mutation, knock-in and overexpression models are used to test the function of trehalose metabolic genes.
What is the GO ID for trehalose metabolic process?
The GO ID is GO:0005991, and the official name is trehalose metabolic process.
Conclusion
GO:0005991 trehalose metabolic process is a compact but biologically rich ontology term that connects sugar chemistry to stress survival, microbial pathogenesis and plant development. Its study spans bacteria, fungi, plants and invertebrates, and it remains a model for understanding how a single metabolite can serve both as a protectant and as a signal. With CRISPR-based knockout, point-mutation, knock-in and overexpression models, researchers can now dissect the pathway with precision and link specific genes to measurable phenotypes.
References
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- 2. Paul M. 2007. Trehalose 6-phosphate.. Curr Opin Plant Biol 10(3):303-9 PMID: 17434789
- 3. Kalscheuer R et al.. 2014. Genetics of Mycobacterial Trehalose Metabolism.. Microbiol Spectr 2(3) PMID: 26103976
- 4. Rojas BE et al.. 2023. Trehalose 6-phosphate metabolism in C(4) species.. Curr Opin Plant Biol 72:102347 PMID: 36806837
- 5. Sharma E et al.. 2023. Trehalose and its Diverse Biological Potential.. Curr Protein Pept Sci 24(6):503-517 PMID: 37282635
- 6. Argüelles JC. 2014. Why can't vertebrates synthesize trehalose?. J Mol Evol 79(3-4):111-6 PMID: 25230776
- 7. Eleutherio E et al.. 2015. Revisiting yeast trehalose metabolism.. Curr Genet 61(3):263-74 PMID: 25209979
- 8. Ruhal R et al.. 2013. Trends in bacterial trehalose metabolism and significant nodes of metabolic pathway in the direction of trehalose accumulation.. Microb Biotechnol 6(5):493-502 PMID: 23302511
