Trehalose analogues are emerging as valuable tools for investigating Mycobacterium tuberculosis, but progress in this area is slow due to the difficulty in synthesizing these compounds. Here, we report a chemoenzymatic synthesis of trehalose analogues that employs the heat-stable enzyme trehalose synthase (TreT) from the hyperthermophile Thermoproteus tenax. By using TreT, various trehalose analogues were prepared quickly (1 h) in high yield (up to >99 % by HPLC) in a single step from readily available glucose analogues. To demonstrate the utility of this method in mycobacteria research, we performed a simple "one-pot metabolic labeling" experiment that accomplished probe synthesis, metabolic labeling, and imaging of M. smegmatis in a single day with only TreT and commercially available materials. Trehalose tools for TB: A one-step chemoenzymatic method for the rapid and efficient synthesis of trehalose analogues was developed. This method enabled facile preparation and administration of a trehalose-based probe for detecting mycobacteria, which might enable the development of new diagnostic tools for tuberculosis (TB) research.
- chemoenzymatic synthesis
- click chemistry