Enzyme - Alpha,alpha-trehalose-phosphate synthase (UDP-forming)

Alternative Name(s)
  • Trehalosephosphate-UDP glucosyltransferase.
  • UDP-glucose--glucose-phosphate glucosyltransferase.
  • Trehalose 6-phosphate synthase.
  • Trehalose phosphate synthetase.
  • Trehalose 6-phosphate synthetase.
  • Transglucosylase.
  • Trehalose phosphate synthase.

Catalytic Activity

D-glucose 6-phosphate + UDP-alpha-D-glucose = alpha,alpha-trehalose 6-phosphate + H(+) + UDP


There are no Cofactors for this Enzyme

Reaction Mechanism

    Escherichia coli trehalose-6-phosphate synthase is part of the glycosyl transferase family 20, the retaining glycosyl transferases. It is able to catalyse the condensation between Glucose-6-phosphate and UDP-glucose to form trehalose-6-phosphate, an important metabolite for many bacteria and plants. Interest in the enzyme stems both from the study of the unusual reaction mechanism and the fact that it plays a key role in bacterial cell wall synthesis in M. tuberculosis, so is a possible target for antibiotics. It displays sequence and structural identity with the glycogen phosphorylases in particular, suggesting a common mechanism and evolutionary origin. Also found to be similar is the pseudo-glycosyltransferase VldE involved in validoxylamine A 7'-phosphate synthesis.

    The reaction mechanism proceeds via an SNi type, meaning internal return whereby nucleophilic attack occurs on the same side as the leaving group departs. The ring oxygen of the UDP glucose donates electron density to C1 to allow the UDP to leave the molecule. This forms a shortly lived oxocarbenium ion stabilised by His 154 and Asp 361. Nucleophilic attack from the glucose-6-phosphate OH group on the anomeric carbon of glucose ensures that the configuration is retained to give the disaccharide product. UDP phosphate forming a hydrogen bond to the OH 1 on the acceptor molecule stabilises the negative charges developing on pyrophosphate, promoting UDP as a leaving group and also positions glucose-6-phosphate for nucleophilic attack. The activation of the OH towards nucleophilic attack is accomplished by the UDP moiety acting as a general base to remove a proton.
    Catalytic Residues
    AA Uniprot Uniprot Resid PDB PDB Resid
    His P31677 155 1uqt 155
    Asp P31677 362 1uqt 362
    Step Components

    overall reactant used, proton transfer, overall product formed, intermediate formation, bimolecular nucleophilic substitution, heterolysis, elimination (not covered by the Ingold mechanisms)

    Step 1.

    Cleavage of glycosidic bond between C1 and O while hydrogen bonds form between the OH on acceptor and O of phosphate.

    Step 2.

    Oxocarbenium ion intermediate generated is very short-lived. Concomitant Proton transfer and nucleophilic attack of O1 on glucose-6-phosphate on anomeric carbon on glucose intermediate.


    The products of the reaction.

Reaction Parameters

There are no kinetic parameters information for this Enzyme

Associated Proteins

Protein name Organism
Alpha,alpha-trehalose-phosphate synthase [UDP-forming] 1 Mouse-ear cress
Alpha,alpha-trehalose-phosphate synthase [UDP-forming] 56 kDa subunit Baker's yeast
Alpha,alpha-trehalose-phosphate synthase [UDP-forming] Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139)
Probable alpha,alpha-trehalose-phosphate synthase [UDP-forming] 2 Mouse-ear cress
Trehalose-6-phosphate synthase Escherichia coli (strain K12)