Chemically modified versions of trehalose, called trehalose analogues, have potential applications in a variety of industries. Azide-modified versions, for example, can be incorporated into the cell wall of the global pathogen Mycobacterium tuberculosis to enable its detection. Unfortunately, the production of trehalose analogues has remained limited by the synthetic challenges presented by the nature of trehalose’s C2-symmetry and its 1,1-α,α glycosidic bond. Multi-step chemical synthesis strategies have been developed to address this problem, but these strategies are limited due to low overall efficiency. Here, we present a chemoenzymatic method that enables the rapid synthesis and purification of trehalose analogues using the trehalose synthase enzyme (TreT) from the hyperthermophilic archeaon Thermoproteus tenax, which joins a uridine diphosphate glucose donor with a glucose analogue acceptor to generate a trehalose analogue in a single step. After optimization efforts described here, in particular the purification protocol, the TreT method enabled the cost-effective and “green” synthesis of trehalose analogues from commercial starting materials in less than a day.

One-step chemoenzymatic synthesis of trehalose analogues

251st National Meeting (2016)

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