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Trehalose-6-phosphate synthase or Trehalose-6-phosphate phosphatase (TPS1 (trehalose-6-phosphate synthase), TPS2 (trehalose-6-phosphate phosphatase))

Target
TPS1 (trehalose-6-phosphate synthase), TPS2 (trehalose-6-phosphate phosphatase)
Molecular classification
Enzyme, Glucosyltransferase (Tps1), Phosphatase (Tps2), Metabolic enzyme complex (in fungi, with regulatory subunits)
01

Overview

The **trehalose biosynthetic pathway enzymes** refer most commonly to two key enzymes: **trehalose-6-phosphate synthase** (TPS1, Tps1p) and **trehalose-6-phosphate phosphatase** (TPS2, Tps2p). Together, they catalyze the stepwise synthesis of trehalose, a nonreducing disaccharide, from UDP-glucose and glucose-6-phosphate[1][2][3][4]. TPS1 catalyzes the production of trehalose-6-phosphate (T6P), and TPS2 dephosphorylates T6P to yield free trehalose. In fungi, these enzymes may exist as larger multi-protein complexes that include regulatory subunits such as Tps3 and Tsl1[1][3][4]. Trehalose biosynthetic enzymes are **absent in mammals**, making the pathway a validated and highly selective target for antifungal therapies[2][3]. Inhibition of either Tps1 or Tps2 in pathogenic fungi (such as *Candida albicans*, *Cryptococcus neoformans*, and *Aspergillus fumigatus*) impairs stress tolerance, reduces infectivity, and may cause accumulation of cytotoxic intermediates[2][3]. Chemical inhibitors (e.g., validoxylamine A for Tps1) are under investigation and provide potential selective antifungal strategies[5]. This pathway is also found in plants, insects, and bacteria, playing roles in stress adaptation, development, and carbohydrate metabolism[1][3][6]. If needed, specify the particular enzyme (TPS1 or TPS2) for more structured data; "trehalose biosynthetic pathway enzyme" most often refers to these canonical two enzymes.

Other names
Tps1Tps2Tps3 (complex subunit, non-enzymatic in some fungi)trehalose biosynthetic enzymesTPSTPP
02

Mechanism of action

Inhibition of trehalose biosynthetic enzymes leads to loss of stress tolerance and cell death in fungi, particularly under host-imposed stresses

03

Biological functions

Stress response (osmotic, thermal, oxidative)Energy homeostasisRegulation of sugar metabolismProtection of proteins and membranesCell wall biosynthesis (indirect)
04

Disease associations

Infection (pathogenic fungi)Other (contributes to fungal virulence/fitness)
05

Safety considerations

Essentiality of pathway in humans is absent, so targeting this pathway in fungi or plants is expected to present low host toxicitySelectivity for pathogen vs. commensal/beneficial organisms remains an open concern for broad-spectrum application
06

Interacting drugs

Validoxylamine A (inhibitor, binds TPS1)

1 more in the full profile.

07

Biomarkers

Trehalose-6-phosphate levels (for cellular stress and pathway inhibition in research)Trehalose (as a stress marker)

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