Vitamin in the Crosshairs: Targeting Pantothenate and Coenzyme A Biosynthesis for New Antituberculosis Agents.

ABSTRACT: Despite decades of dedicated research, there remains a dire need for new drugs against tuberculosis (TB). Current therapies are generations old and problematic. Resistance to these existing therapies results in an ever-increasing burden of patients with disease that is difficult or impossible to treat. Novel chemical entities with new mechanisms of action are therefore earnestly required. The biosynthesis of coenzyme A (CoA) has long been known to be essential in Mycobacterium tuberculosis (Mtb), the causative agent of TB. The pathway has been genetically validated by seminal studies in vitro and in vivo. In Mtb, the CoA biosynthetic pathway is comprised of nine enzymes: four to synthesize pantothenate (Pan) from l-aspartate and α-ketoisovalerate; five to synthesize Co

SUBMITTER: Butman HS 

PROVIDER: S-EPMC7770189 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature