Trehalose is a critical component of the cell wall of mycobacteria, including the pathogenic <i>Mycobacterium tuberculosis</i>. It is also absent from humans, making it a potential drug target. However, modification to the structure of trehalose using traditional organic synthesis is difficult, time-consuming and often results in low yield, limiting some applications of trehalose analogs. In order to surmount these obstacles, we used the enzyme TreT to create trehalose analogs from simple, commercially available starting materials. We found that the enzyme was promiscuous in accepting modified substrates and could convert them into trehalose analogs at most positions on the sugar. We were able to synthesize several analogs in &gt;99% yield in as little as an hour. We were also able to demonstrate that the analogs could be taken up by mycobacteria and incorporated into their cell wall. Facile, rapid chemoenzymatic synthesis of trehalose analogs may allow noninvasive imaging of infection as well as a new class of antimicrobial compounds.

Chemoenzymatic synthesis of trehalose analogs for targeting mycobacteria

251st National Meeting (2016)

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