Inhibitors of Mycobacterium tuberculosis EgtD target both substrate binding sites to limit hercynine production.

Ergothioneine (EGT) is a low molecular weight histidine betaine essential in all domains of life but only synthesized by selected few organisms. Synthesis of EGT by Mycobacterium tuberculosis (M. tb) is critical for maintaining bioenergetic homeostasis and protecting the bacterium from alkylating agents, oxidative stress, and anti-tubercular drugs.

Total Synthesis of Tetrahydrolipstatin, Its Derivatives, and Evaluation of Their Ability to Potentiate Multiple Antibiotic Classes against Species.

Tetrahydrolipstatin (THL, ) has been shown to inhibit both mammalian and bacterial α/β hydrolases. In the case of bacterial systems, THL is a known inhibitor of several hydrolases involved in mycomembrane biosynthesis. Herein we report a highly efficient eight-step asymmetric synthesis of THL using a route that allows modification of the THL α-chain substituent to afford compounds through .

Characterization of Tetrahydrolipstatin and Stereoderivatives on the Inhibition of Essential Mycobacterium tuberculosis Lipid Esterases.

Tetrahydrolipstatin (THL) is a covalent inhibitor of many serine esterases. In mycobacteria, THL has been found to covalently react with 261 lipid esterases upon treatment of Mycobacterium bovis cell lysate. However, the covalent adduct is considered unstable in some cases because of the hydrolysis of the enzyme-linked THL adduct resulting in catalytic turnover.