A D-phenylalanine-benzoxazole derivative uncovers redundancy in the pantothenate biosynthetic pathway of Mycobacterium tuberculosis

Michael Pepi
New drugs and new targets are urgently needed to treat tuberculosis. We discovered the D-phenylalanine-benzoxazole Q112 displays potent antibacterial activity against Mycobacterium tuberculosis in multiple media and in macrophage infections. Metabolomic profiling experiments indicate that Q112 has a unique mechanism of action compared to other antitubercular agents. Q112 perturbs the essential pantothenate/CoA biosynthetic pathway, depleting pantoate while increasing ketopantoate, as would be expected if ketopantoate reductase (KPR) were inhibited. We searched for alternative KPRs since...
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