Session: General Posters:

Trehalosamine is a naturally occurring aminoglycoside antibiotic first isolated from Streptomyces in 1957, and around that time it was found to be a potent inhibitor of Mycobacterium tuberculosis (Mtb) growth. Although having promising activity against Mtb, no follow-up studies have been published on trehalosamine. The challenges associated with isolation and chemical synthesis of trehalosamine and related structures makes them poorly accessible for further investigation. To obtain this molecule and its regioisomers for detailed structure–activity relationship and mode-of-action studies, efficient synthetic approaches are required. In this study, we investigated the ability of the glycosyltransferase enzyme TreT to enable 2-step chemoenzymatic syntheses of trehalosamine and its regioisomers 3-trehalosamine, 5-trehalosamine, and 6-trehalosamine using 3-azido glucose, nojirimycin, and 6-azido glucose as acceptor molecules, respectively. Although TreT has a wide range of substrate tolerance, we have found that modification of the 4-position of acceptor molecule is not well-tolerated by the enzyme. Therefore, 4-trehalosamine was synthesized via chemical synthesis. Combining both chemical and chemoenzymatic approaches, we have gained access to trehalosamine and at least four of its positional isomers. This work sets the stage for further investigation and application of trehalosamine derivatives as anti-tubercular compounds.

Benjamin Swarts

Central Michigan University

Appearances