Trehalose synthesis via trehalose 6-phosphate and trehalase hydrolysis

Trehalose (alpha-D-glucopyranosyl alpha-D-glucopyranoside) is a non-reducing glucose disaccharide used as a reserve carbohydrate and stress protectant by fungi, bacteria, invertebrates and plants. This module covers its synthesis through the phosphorylated intermediate and its hydrolysis. A retaining glycosyltransferase of GT-20 family, trehalose-6-phosphate synthase (TPS, OtsA), transfers glucose from UDP-glucose to glucose 6-phosphate to form alpha,alpha-trehalose 6-phosphate (T6P). A HAD-superfamily trehalose-6-phosphate phosphatase (TPP, OtsB) then removes the phosphate to release free trehalose. The phosphatase is either a standalone OtsB-type enzyme (bacteria, plants) or the C-terminal phosphatase domain of a larger TPS2-type protein that also carries an inactive GT-20-like domain (fungi). In yeasts the two catalytic subunits form a cytosolic trehalose synthase complex together with large TSL1/TPS3-type regulatory subunits, which also carry GT-20-like domains and are needed for full activity and stability of the complex. Trehalose is hydrolysed to two glucose molecules by trehalases. A cytosolic glycoside hydrolase family 37 neutral trehalase mobilises intracellular trehalose, and an extracellular or periplasmic trehalase (GH65 acid trehalase in budding yeast, GH37 TreA in enterobacteria) hydrolyses external trehalose. T6P also acts as a signalling metabolite (for example as a hexokinase inhibitor in budding yeast), which is a separate role of the pathway intermediate. The other trehalose routes (TreY/TreZ and TreS from alpha-glucans, trehalose phosphorylases), the supply of UDP-glucose and glucose 6-phosphate, and trehalose transport are outside the boundary.

MODULE:trehalose_metabolismDRAFTCONCRETEMetabolic Pathwaymodules/trehalose_metabolism.yaml
trehalose metabolic processGO:0005991
GO:0005991
trehalose metabolic process
Module-level process concept covering synthesis and hydrolysis of trehalose.
GO:0005992
trehalose biosynthetic process
Process concept for the TPS/TPP synthesis arm.
GO:0005993
trehalose catabolic process
Process concept for the trehalase hydrolysis arm.
GO:0005946
alpha,alpha-trehalose-phosphate synthase complex (UDP-forming)
Complex term for the fungal TPS1/TPS2/TSL1/TPS3 trehalose synthase complex.
YeastPathways:TRESYN-PWY
trehalose biosynthesis I (S. cerevisiae, SGD YeastPathways)
YeastCyc lists TREHALOSE6PSYN-RXN (TPS1) and TREHALOSEPHOSPHA-RXN (TPS2). Both assignments were retained. The pathway comment describes the regulatory subunits TSL1 and TPS3 but they are not attached to any reaction; they were added here as regulatory subunits of the complex.
YeastPathways:TREDEG-YEAST-PWY
trehalose degradation (S. cerevisiae, SGD YeastPathways)
YeastCyc lists TREHALA-RXN with NTH1 and ATH1. Both were retained in different compartment variants. NTH2, the NTH1 paralog shown to be a functional cytosolic trehalase (PMID:18065618), was added.
PMID:11152943
Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae.
Review of synthesis and degradation of the two yeast glucose stores, glycogen and trehalose, and their regulation (cited by YeastPathways for both trehalose frames).
Glycogen and trehalose are the two glucose stores of yeast cells.
PMID:9837904
Composition and functional analysis of the Saccharomyces cerevisiae trehalose synthase complex.
Tps1 (TPS) and Tps2 (TPP) are in the trehalose synthase complex with regulatory subunits Tsl1 and Tps3; deletion of TPS1 abolishes TPS activity, deletion of TPS2 abolishes TPP activity, and TSL1/TPS3 are partially redundant subunits needed for full activity and stability.
We conclude that Tps3 is a fourth subunit of the complex with functions partially redundant to those of Tsl1.
PMID:1425702
Characterization of the 56-kDa subunit of yeast trehalose-6-phosphate synthase and cloning of its gene reveal its identity with the product of CIF1, a regulator of carbon catabolite inactivation.
TPS1 encodes the 56-kDa trehalose-6-phosphate synthase subunit.
A mutant obtained by disruption of TPS1 had a very low activity of trehalose-6-phosphate synthase
PMID:8444170
Disruption of TPS2, the gene encoding the 100-kDa subunit of the trehalose-6-phosphate synthase/phosphatase complex in Saccharomyces cerevisiae, causes accumulation of trehalose-6-phosphate and loss of trehalose-6-phosphate phosphatase activity.
TPS2 is the structural gene for trehalose-6-phosphate phosphatase.
These results suggest that TPS2 codes for the structural gene of the trehalose-6-phosphate phosphatase.
PMID:8404905
Cloning of two related genes encoding the 56-kDa and 123-kDa subunits of trehalose synthase from the yeast Saccharomyces cerevisiae.
TSL1 encodes the 123-kDa subunit; its N-terminal region modulates the phosphate inhibition and fructose 6-phosphate activation of T6P synthase.
These results suggest that this N-terminal part confers regulatory properties upon the Tre6P synthase activity.
PMID:8809751
Evidence for trehalose-6-phosphate-dependent and -independent mechanisms in the control of sugar influx into yeast glycolysis.
T6P inhibits yeast hexokinases, a signalling role of the pathway intermediate that is outside the module boundary.
Furthermore, we have confirmed that tre-6-P inhibits the hexokinases in vitro.
PMID:8444853
Molecular analysis of the neutral trehalase gene from Saccharomyces cerevisiae.
NTH1 encodes the neutral trehalase.
The gene of neutral trehalase was cloned by complementation of a neutral trehalase-deficient yeast mutant
PMID:18065618
New insights into trehalose metabolism by Saccharomyces cerevisiae: NTH2 encodes a functional cytosolic trehalase, and deletion of TPS1 reveals Ath1p-dependent trehalose mobilization.
NTH2 encodes a functional trehalase involved in trehalose mobilization.
we showed that NTH2, a paralog of NTH1, encodes a functional trehalase that is implicated in trehalose mobilization.
PMID:8764988
Purification and biochemical characterization of the ATH1 gene product, vacuolar acid trehalase, from Saccharomyces cerevisiae.
Purified acid trehalase is the ATH1 gene product.
We have purified ATH and shown that it is the ATH1 gene product
PMID:15128531
Two distinct pathways for trehalose assimilation in the yeast Saccharomyces cerevisiae.
More than 90% of Ath1 activity is extracellular, so the acid trehalase acts mainly outside the plasma membrane rather than in the vacuole.
we showed that more than 90% of the activity of Ath1p is extracellular, splitting of the disaccharide into glucose.
PMID:8045430
Analysis of the otsBA operon for osmoregulatory trehalose synthesis in Escherichia coli and homology of the OtsA and OtsB proteins to the yeast trehalose-6-phosphate synthase/phosphatase complex.
E. coli OtsA (TPS) and OtsB (TPP) are separate enzymes. OtsA is homologous to TPS1, the N-terminal part of TPS2 and an internal region of TSL1; OtsB is homologous only to the C-terminal part of TPS2.
OtsB has homology to the C-terminal part of TPS2, but no homology to the other subunits.
PMID:12498887
Insights into trehalose synthesis provided by the structure of the retaining glucosyltransferase OtsA.
Structure of E. coli OtsA, the retaining GT-20 glucosyltransferase that condenses UDP-glucose and glucose 6-phosphate.
The classical pathway for trehalose synthesis involves the condensation of UDP-glucose and glucose-6-phosphate to afford trehalose-6-phosphate, catalyzed by the retaining glycosyltransferase OtsA.
PMID:8021171
Trehalose-6-P synthase is dispensable for growth on glucose but not for spore germination in Schizosaccharomyces pombe.
S. pombe tps1+ encodes trehalose-6-phosphate synthase that complements a S. cerevisiae tps1 mutant.
The tps1+ gene expressed from its own promoter could complement the lack of trehalose-6-P synthase in S. cerevisiae tps1 mutants.
PMID:11004189
Characterization of tpp1(+) as encoding a main trehalose-6P phosphatase in the fission yeast Schizosaccharomyces pombe.
S. pombe tpp1+ encodes the main trehalose-6-phosphate phosphatase.
Disruption of tpp1(+) caused in vivo accumulation of trehalose-6P upon heat shock
PMID:12153582
Molecular interaction of neutral trehalase with other enzymes of trehalose metabolism in the fission yeast Schizosaccharomyces pombe.
S. pombe Tps1, Tpp1 and the neutral trehalase Ntp1 interact in vitro and form complexes.
tps1+ (coding for trehalose-6-P synthase, Tps1p), ntp1+ (encoding neutral trehalase, Ntp1p) and tpp1+ (that codes for trehalose-6-P phosphatase, Tpp1p), interact in vitro with each other and with themselves to form protein complexes.
PANTHER:PTHR10788
TREHALOSE-6-PHOSPHATE SYNTHASE
GT-20 family containing TPS (OtsA, TPS1), the fungal TPS2-type phosphatases and the TSL1/TPS3 regulatory subunits, as subfamilies.
10Nodes
5Parts
2Variant Sets
4Variants
7Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:trehalose_metabolism deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

11 gene-function check(s) reflected in core functions · 0 conflict(s) · 8 evidence or coverage gap(s) (26 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
tps_activity TPS1 (Saccharomyces cerevisiae)
UniProtKB:Q00764
Family Representative 		alpha,alpha-trehalose-phosphate synthase (UDP-forming) activity
GO:0003825 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tps_activity tps1 (Schizosaccharomyces pombe)
UniProtKB:P40387
Family Representative 		alpha,alpha-trehalose-phosphate synthase (UDP-forming) activity
GO:0003825 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tps_activity otsA (Escherichia coli K-12)
UniProtKB:P31677
Family Representative 		alpha,alpha-trehalose-phosphate synthase (UDP-forming) activity
GO:0003825 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
tps2_type_tpp_activity TPS2 (Saccharomyces cerevisiae)
UniProtKB:P31688
Family Representative 		trehalose-phosphatase activity
GO:0004805 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tps2_type_tpp_activity tpp1 (Schizosaccharomyces pombe)
UniProtKB:P78875
Family Representative 		trehalose-phosphatase activity
GO:0004805 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tps2_type_tpp_activity tps2 (Schizosaccharomyces pombe)
UniProtKB:O14145
Family Representative 		trehalose-phosphatase activity
GO:0004805 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
otsb_tpp_activity otsB (Escherichia coli K-12)
UniProtKB:P31678
Family Representative 		trehalose-phosphatase activity
GO:0004805 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
tps_regulatory_subunit_activity TSL1 (Saccharomyces cerevisiae)
UniProtKB:P38427
Family Representative 		enzyme regulator activity
GO:0030234 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tps_regulatory_subunit_activity TPS3 (Saccharomyces cerevisiae)
UniProtKB:P38426
Family Representative 		enzyme regulator activity
GO:0030234 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
tps_regulatory_subunit_activity tps3 (Schizosaccharomyces pombe)
UniProtKB:O14081
Family Representative 		enzyme regulator activity
GO:0030234 		Function Unreviewed
No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
tps_regulatory_subunit_activity SPAC22F8.05 (Schizosaccharomyces pombe)
UniProtKB:Q9UUI7
Family Representative 		enzyme regulator activity
GO:0030234 		Function Unreviewed
No retained annotation or core molecular function supports this GO assertion. Missing or broader evidence is a coverage gap, not proof the activity is absent.
neutral_trehalase_activity NTH1 (Saccharomyces cerevisiae)
UniProtKB:P32356
Family Representative 		alpha,alpha-trehalase activity
GO:0004555 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
neutral_trehalase_activity NTH2 (Saccharomyces cerevisiae)
UniProtKB:P35172
Family Representative 		alpha,alpha-trehalase activity
GO:0004555 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
neutral_trehalase_activity ntp1 (Schizosaccharomyces pombe)
UniProtKB:O42893
Family Representative 		alpha,alpha-trehalase activity
GO:0004555 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
neutral_trehalase_activity treF (Escherichia coli K-12)
UniProtKB:P62601
Family Representative 		alpha,alpha-trehalase activity
GO:0004555 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
acid_trehalase_activity ATH1 (Saccharomyces cerevisiae)
UniProtKB:P48016
Family Representative 		alpha,alpha-trehalase activity
GO:0004555 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
periplasmic_trea_activity treA (Escherichia coli K-12)
UniProtKB:P13482
Family Representative 		alpha,alpha-trehalase activity
GO:0004555 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
tps_activity catalytic GT-20 trehalose-6-phosphate synthase (TPS1/OtsA subfamily)
PANTHER:PTHR10788:SF106
Family 		alpha,alpha-trehalose-phosphate synthase (UDP-forming) activity
GO:0003825 		Family Supported
Family review supports GO:0003825 for PANTHER:PTHR10788:SF106. Catalysed by class I TPS (SF106), as trehalose_metabolism selects; accepted by S. cerevisiae TPS1 and S. pombe tps1. The regulatory subunits (TPS3, TSL1 in SF15; S. pombe SPAC22F8.05 in SF119) have degenerate synthase domains and only contribute to the activity of the complex; their reviews record it as contributes_to.
tps2_type_tpp_activity TPS2-type trehalose-6-phosphate phosphatase subfamilies of the GT-20 family
PANTHER:PTHR10788:SF123
Family 		trehalose-phosphatase activity
GO:0004805 		Family Function Unreviewed
Family review leaves GO:0004805 UNRESOLVED. No subfamily list states this cleanly. The phosphatase subfamilies SF123 and SF121 catalyse it (TPS2, tps2, tpp1 accept it), and TPS3/TSL1 (SF15) contribute to the complex activity without catalysing it. But SF106 is mixed: Drosophila Tps1 is a bifunctional TPS-TPP whose phosphatase domain is active (IDA, PMID:27469628, accepted in genes/DROME/Tps1), while the fungal SF106 members (TPS1, tps1, Candida TPS1; 478-513 residues) are synthase-only, with no HAD-like or Trehalose_PPase InterPro domain in UniProt, while the worm and Dictyostelium SF106 members carry a HAD-like domain but are untested for activity. Listing SF106 would assert the activity for the fungal synthases; omitting it contradicts the fly evidence.
tps2_type_tpp_activity TPS2-type trehalose-6-phosphate phosphatase subfamilies of the GT-20 family
PANTHER:PTHR10788:SF121
Family 		trehalose-phosphatase activity
GO:0004805 		Family Function Unreviewed
Family review leaves GO:0004805 UNRESOLVED. No subfamily list states this cleanly. The phosphatase subfamilies SF123 and SF121 catalyse it (TPS2, tps2, tpp1 accept it), and TPS3/TSL1 (SF15) contribute to the complex activity without catalysing it. But SF106 is mixed: Drosophila Tps1 is a bifunctional TPS-TPP whose phosphatase domain is active (IDA, PMID:27469628, accepted in genes/DROME/Tps1), while the fungal SF106 members (TPS1, tps1, Candida TPS1; 478-513 residues) are synthase-only, with no HAD-like or Trehalose_PPase InterPro domain in UniProt, while the worm and Dictyostelium SF106 members carry a HAD-like domain but are untested for activity. Listing SF106 would assert the activity for the fungal synthases; omitting it contradicts the fly evidence.
otsb_tpp_activity standalone OtsB-type trehalose-6-phosphate phosphatase
PANTHER:PTHR43768
Family 		trehalose-phosphatase activity
GO:0004805 		Family Supported
Family review supports GO:0004805 FAMILY_WIDE. Asserted by trehalose_metabolism; all Swiss-Prot members are named trehalose-phosphate phosphatases.
tps_regulatory_subunit_activity TSL1/TPS3-type regulatory subunits of the GT-20 family
PANTHER:PTHR10788:SF15
Family 		enzyme regulator activity
GO:0030234 		Family Supported
Family review supports GO:0030234 for PANTHER:PTHR10788:SF15. Regulatory large subunits of the trehalose synthase complex, as trehalose_metabolism selects: S. cerevisiae TSL1 and TPS3 (SF15) and the S. pombe 100 kDa subunits (SF119 holds SPAC22F8.05). The catalytic TPS1 and TPS2 subfamilies are not regulators.
tps_regulatory_subunit_activity TSL1/TPS3-type regulatory subunits of the GT-20 family
PANTHER:PTHR10788:SF119
Family 		enzyme regulator activity
GO:0030234 		Family Supported
Family review supports GO:0030234 for PANTHER:PTHR10788:SF119. Regulatory large subunits of the trehalose synthase complex, as trehalose_metabolism selects: S. cerevisiae TSL1 and TPS3 (SF15) and the S. pombe 100 kDa subunits (SF119 holds SPAC22F8.05). The catalytic TPS1 and TPS2 subfamilies are not regulators.
neutral_trehalase_activity glycoside hydrolase family 37 trehalase
PANTHER:PTHR23403
Family 		alpha,alpha-trehalase activity
GO:0004555 		Family Supported
Family review supports GO:0004555 FAMILY_WIDE. Asserted by trehalose_metabolism for NTH1, NTH2, ntp1 (base family) and TreA (SF1); accepted by every reviewed member.
acid_trehalase_activity glycoside hydrolase family 65 acid trehalase
PANTHER:PTHR11051:SF8
Family 		alpha,alpha-trehalase activity
GO:0004555 		Family Supported
Family review supports GO:0004555 for PANTHER:PTHR11051:SF8. The fungal acid trehalases in SF8, as trehalose_metabolism selects for S. cerevisiae ATH1. Animal PGGHG in the same subfamily is a different glucosidase.
periplasmic_trea_activity periplasmic GH37 trehalase
PANTHER:PTHR23403:SF1
Family 		alpha,alpha-trehalase activity
GO:0004555 		Family Supported
Family review supports GO:0004555 FAMILY_WIDE. Asserted by trehalose_metabolism for NTH1, NTH2, ntp1 (base family) and TreA (SF1); accepted by every reviewed member.

Gene-review completeness (13/17 grounded genes reviewed)

12 complete review(s) · 7 with deep research · 4 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
ATH1 P48016 ✓ ✓ ✓
NTH1 P32356 ✓ ✓ ✓
NTH2 P35172 ✓ 11/12 ✓
ntp1 O42893 ✓ ✓ ✗
treA (Escherichia coli K-12) P13482 ✗ — —
otsA (Escherichia coli K-12) P31677 ✗ — —
otsB (Escherichia coli K-12) P31678 ✗ — —
treF (Escherichia coli K-12) P62601 ✗ — —
SPAC22F8.05 Q9UUI7 ✓ ✓ ✗
SPAC2E11.16c O14081 ✓ ✓ ✗
tpp1 P78875 ✓ ✓ ✗
tps1 P40387 ✓ ✓ ✗
TPS1 Q00764 ✓ ✓ ✓
tps2 O14145 ✓ ✓ ✗
TPS2 P31688 ✓ ✓ ✓
TPS3 P38426 ✓ ✓ ✓
TSL1 P38427 ✓ ✓ ✓

Details

Trehalose synthesis via trehalose 6-phosphate and trehalase hydrolysisMetabolic Pathwaytrehalose_metabolism
trehalose metabolic processGO:0005991

NEW module (YeastPathways crosswalk, 2026-10) generalising TRESYN-PWY and TREDEG-YEAST-PWY into the OtsA/OtsB-type (TPS/TPP) trehalose synthesis plus trehalase hydrolysis module found in fungi, bacteria, invertebrates and plants. Corrections and additions to YeastCyc: (1) TSL1 and TPS3 are described in the TRESYN-PWY comment but not attached to a reaction; they are modelled as an optional regulatory-subunit part of the trehalose synthase complex (GO:0005946). Their function is regulatory, not catalytic, so they get GO:0030234 enzyme regulator activity, matching the PomBase GO-CAM. (2) NTH2 is added as a second cytosolic trehalase (PMID:18065618). Its physiological contribution is minor compared with NTH1. (3) ATH1 is placed in the periplasmic space rather than the vacuole: more than 90% of Ath1 activity is extracellular (PMID:15128531). The YeastCyc comment agrees. Both catalytic yeast subunits are cytosolic, as in the YeastPathways GO-CAM. Architecture: the TPP step has a fungal TPS2-type variant and a standalone OtsB variant. In S. pombe both tps2 (SPAC3G6.09c) and tpp1 (SPAC19G12.15c) are TPS2-type proteins; tpp1 is the main phosphatase by genetics (PMID:11004189), and the GO-CAM types both as TPP. S. pombe SPAC22F8.05 is a regulator in the GO-CAM only on phylogenetic grounds and falls in a different PANTHER subfamily (SF119) from TSL1/TPS3 (SF15); its role is not experimentally established. GO-CAM disagreements: the YeastPathways TRESYN-PWY model omits TSL1/TPS3 and has no causal edge between TPS and TPP; there is no YeastPathways GO-CAM for TREDEG-YEAST-PWY. The PomBase model includes pgm1, uge1 and gal10 sugar-phosphate supply activities (Leloir pathway) that are outside this module. Out of scope: TreY/TreZ and TreS routes (modules trey_trez_trehalose_biosynthesis and bacterial_trehalose_synthesis_from_alpha_glucans), trehalose phosphorylases, trehalose transport (AGT1/MAL11), the PKA/Bmh control of NTH1, and T6P signalling to hexokinase (PMID:8809751). In plants most TPS-like and TPP-like genes are regulatory or signalling proteins; plant exemplars are not included.

Connections

Trehalose made in the cytosol is the substrate mobilised by the cytosolic neutral trehalase.
Part 1: trehalose synthesis through trehalose 6-phosphate
UDP-glucose + glucose 6-phosphate to trehaloseMetabolic Pathwaytrehalose_synthesis
trehalose biosynthetic processGO:0005992

Connections

tps_step -> tpp_step Precedes
tps_complex_regulatory_subunits -> tps_step Positively Regulates
TSL1/TPS3 subunits raise and modulate TPS activity within the complex.
Part 1: trehalose-6-phosphate synthase
UDP-glucose + glucose 6-phosphate to trehalose 6-phosphate + UDPReactiontps_step

Annotons

Trehalose-6-phosphate synthase (TPS1/OtsA)
tps_activity
Participant: Family: catalytic GT-20 trehalose-6-phosphate synthase (TPS1/OtsA subfamily)
Family:
catalytic GT-20 trehalose-6-phosphate synthase (TPS1/OtsA subfamily)PANTHER:PTHR10788:SF106 PANTHER names this subfamily after a Drosophila clone; UniProt places S. cerevisiae TPS1, S. pombe tps1 and E. coli OtsA in it.
Representative Members: TPS1 (Saccharomyces cerevisiae)UniProtKB:Q00764 tps1 (Schizosaccharomyces pombe)UniProtKB:P40387 otsA (Escherichia coli K-12)UniProtKB:P31677
Required Function:
alpha,alpha-trehalose-phosphate synthase (UDP-forming) activityGO:0003825

Function

alpha,alpha-trehalose-phosphate synthase (UDP-forming) activityGO:0003825
Substrates: UDP-alpha-D-glucose D-glucose 6-phosphate
Products: alpha,alpha-trehalose 6-phosphate UDP

Locations

cytosolGO:0005829

Retaining GT-20 glucosyltransferase that sets both anomeric centres of trehalose 6-phosphate. In budding yeast TPS1 is also needed for growth on glucose through T6P-dependent and T6P-independent control of glycolytic influx; that role is not modelled here.

Part 2: trehalose-6-phosphate phosphatase
trehalose 6-phosphate + H2O to trehalose + phosphateReactiontpp_step
Variant set: Trehalose-6-phosphate phosphatase architecture by enzyme architecture (Exactly One)

The phosphatase chemistry is HAD-superfamily in both variants. In fungi it is the C-terminal domain of a large TPS2-type protein whose N-terminal GT-20-like domain is inactive; in bacteria (and plants) it is a standalone OtsB-type protein from a different PANTHER family.

Fungal TPS2-type phosphatase (GT-20-like plus HAD domains)Reactionfungal_tps2_type_tpp

Annotons

TPS2-type trehalose-6-phosphate phosphatase
tps2_type_tpp_activity
Participant: Family: TPS2-type trehalose-6-phosphate phosphatase subfamilies of the GT-20 family
Family:
TPS2-type trehalose-6-phosphate phosphatase subfamilies of the GT-20 family UniProt places S. cerevisiae TPS2 and S. pombe tps2 in SF123 and S. pombe tpp1 in SF121.
Representative Members: TPS2 (Saccharomyces cerevisiae)UniProtKB:P31688 tpp1 (Schizosaccharomyces pombe)UniProtKB:P78875 tps2 (Schizosaccharomyces pombe)UniProtKB:O14145
Required Function:
trehalose-phosphatase activityGO:0004805

Function

trehalose-phosphatase activityGO:0004805
Substrates: alpha,alpha-trehalose 6-phosphate water
Products: alpha,alpha-trehalose phosphate

Locations

cytosolGO:0005829

HAD phosphatase domain of the trehalose synthase complex that releases trehalose from T6P.

Standalone OtsB-type phosphataseReactionstandalone_otsb_tpp

Annotons

OtsB-type trehalose-6-phosphate phosphatase
otsb_tpp_activity
Participant: Family: standalone OtsB-type trehalose-6-phosphate phosphatase
Family:
standalone OtsB-type trehalose-6-phosphate phosphatasePANTHER:PTHR43768
Representative Members: otsB (Escherichia coli K-12)UniProtKB:P31678
Required Function:
trehalose-phosphatase activityGO:0004805

Function

trehalose-phosphatase activityGO:0004805
Substrates: alpha,alpha-trehalose 6-phosphate water
Products: alpha,alpha-trehalose phosphate

Locations

cytosolGO:0005829

Separate phosphatase protein of the bacterial OtsA/OtsB route.

Part 3: trehalose synthase complex regulatory subunits (fungal) (optional)
TSL1/TPS3-type regulatory subunits of the trehalose synthase complexProtein Complextps_complex_regulatory_subunits

Large non-catalytic subunits that carry GT-20-like and TPP-like domains, bind TPS1 and TPS2 and increase and stabilise their activities. They are fungal and have no counterpart in the bacterial OtsA/OtsB route, so the part is optional at the level of the general module.

alpha,alpha-trehalose-phosphate synthase complex (UDP-forming)GO:0005946

Annotons

TSL1/TPS3-type trehalose synthase regulatory subunit
tps_regulatory_subunit_activity
Participant: Family: TSL1/TPS3-type regulatory subunits of the GT-20 family
Family:
TSL1/TPS3-type regulatory subunits of the GT-20 family UniProt places S. cerevisiae TSL1 and TPS3 and S. pombe tps3 (SPACUNK4.16c) in SF15 and S. pombe SPAC22F8.05 in SF119.
Representative Members: TSL1 (Saccharomyces cerevisiae)UniProtKB:P38427 TPS3 (Saccharomyces cerevisiae)UniProtKB:P38426 tps3 (Schizosaccharomyces pombe)UniProtKB:O14081 SPAC22F8.05 (Schizosaccharomyces pombe)UniProtKB:Q9UUI7

Function

enzyme regulator activityGO:0030234 Raises TPS and TPP activity in the complex and modulates the phosphate inhibition and fructose 6-phosphate activation of TPS.
Targets: trehalose-6-phosphate synthase (TPS1) trehalose-6-phosphate phosphatase (TPS2)

Processes

trehalose biosynthetic processGO:0005992

Locations

cytosolGO:0005829

Regulatory scaffold subunits. Deletion of TSL1 together with TPS3 lowers TPS and TPP activity and trehalose content and destabilises the complex, while TPS1 alone still supports some trehalose synthesis.

Part 2: trehalose hydrolysis by trehalases
trehalose + H2O to 2 D-glucoseReactiontrehalose_hydrolysis
trehalose catabolic processGO:0005993
Variant set: Intracellular versus extracellular trehalases by compartment and enzyme family (One Or More)

The same reaction (EC 3.2.1.28) is carried out by unrelated families in different compartments. Budding yeast has both variants: cytosolic GH37 NTH1/NTH2 mobilise endogenous trehalose and the GH65 acid trehalase ATH1 hydrolyses external trehalose. E. coli likewise has a cytoplasmic (TreF) and a periplasmic (TreA) GH37 trehalase.

Cytosolic neutral trehalase (GH37)Reactionintracellular_neutral_trehalase

Annotons

Cytosolic GH37 neutral trehalase
neutral_trehalase_activity
Participant: Family: glycoside hydrolase family 37 trehalase
Family:
glycoside hydrolase family 37 trehalasePANTHER:PTHR23403 UniProt places the fungal neutral trehalases in PTHR23403:SF6 (CYTOSOLIC NEUTRAL TREHALASE-RELATED) and E. coli TreF in PTHR23403:SF8 (CYTOPLASMIC TREHALASE).
Representative Members: NTH1 (Saccharomyces cerevisiae)UniProtKB:P32356 NTH2 (Saccharomyces cerevisiae)UniProtKB:P35172 ntp1 (Schizosaccharomyces pombe)UniProtKB:O42893 treF (Escherichia coli K-12)UniProtKB:P62601
Required Function:
alpha,alpha-trehalase activityGO:0004555

Function

alpha,alpha-trehalase activityGO:0004555
Substrates: alpha,alpha-trehalose water
Products: alpha-D-glucose beta-D-glucose

Locations

cytosolGO:0005829

Mobilises intracellular trehalose made by the synthesis arm (or taken up by transport). Its activity is post-translationally regulated (PKA phosphorylation in budding yeast; heat-shock activation in fission yeast).

Extracellular or periplasmic trehalaseReactionextracellular_trehalase

Fungal and bacterial extracellular trehalases come from different families (GH65 ATH1 versus GH37 TreA), so each has its own annoton.

Annotons

GH65 acid trehalase (fungal)
acid_trehalase_activity
Participant: Family: glycoside hydrolase family 65 acid trehalase
Family:
glycoside hydrolase family 65 acid trehalasePANTHER:PTHR11051:SF8 PANTHER names this subfamily after the animal member; UniProt places S. cerevisiae ATH1 in it.
Representative Members: ATH1 (Saccharomyces cerevisiae)UniProtKB:P48016
Required Function:
alpha,alpha-trehalase activityGO:0004555

Function

alpha,alpha-trehalase activityGO:0004555
Substrates: alpha,alpha-trehalose water
Products: D-glucose

Locations

periplasmic spaceGO:0042597

Hydrolyses extracellular trehalose for growth on trehalose and, in tps1 mutants loaded with trehalose, exported trehalose. A minor vacuolar pool was the basis of the older name vacuolar acid trehalase.

GH37 periplasmic trehalase (bacterial)
periplasmic_trea_activity
Participant: Family: periplasmic GH37 trehalase
Family:
periplasmic GH37 trehalasePANTHER:PTHR23403:SF1
Representative Members: treA (Escherichia coli K-12)UniProtKB:P13482
Required Function:
alpha,alpha-trehalase activityGO:0004555

Function

alpha,alpha-trehalase activityGO:0004555
Substrates: alpha,alpha-trehalose water
Products: D-glucose

Locations

periplasmic spaceGO:0042597

Bacterial periplasmic trehalase acting on external trehalose.