Characterization of Pantothenate Kinase and Identification of Its Inhibitors From Natural Products.

Coenzyme A (CoA) is a well-known cofactor that plays an essential role in many metabolic reactions in all organisms. In , the most deadly among species that cause malaria, CoA and its biosynthetic pathway have been proven to be indispensable. The first and rate-limiting reaction in the CoA biosynthetic pathway is catalyzed by two putative pantothenate kinases (PanK1 and 2) in this parasite. Here we produced, purified, and biochemically characterized recombinant PanK1 for the first time. PanK1 showed activity using pantetheine besides pantothenate, as the primary substrate, indicating that CoA biosynthesis in the blood stage of can bypass pantothenate. We further developed a robust and reliable screening system to identify inhibitors using recombinant PanK1 and identified four PanK inhibitors from natural compounds.