Probing the ligand preferences of the three types of bacterial pantothenate kinase

Abstract Pantothenate kinase(PanK) catalyzes the transformation of pantothenate to 4′-phosphopantothenate, the first committed stepin coenzymeA biosynthesis. While numerous pantothenate antimetabolitesand PanK inhibitors have been reported for bacterial type I and type II PanKs, only a few weak inhibitors are known for bacterial type III PanK enzymes. Here, a series of pantothenate analogues were synthesized using convenient synthetic methodology. The compounds were exploited as small organic probes to compare the ligand preferences of the three different types of bacterial PanK. Overall, several new inhibitors and substrates were identified for each type of PanK.