Biosynthetic and synthetic strategies for assembling capuramycin-type antituberculosis antibiotics

Abstract

Mycobacterium tuberculosis (Mtb) has recently surpassed HIV/AIDS as the leading cause of death by a single infectious agent. The standard therapeutic regimen against tuberculosis (TB) remains a long, expensive process involving a multidrug regimen, and the prominence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains continues to impede treatment success. An underexplored class of natural products—the capuramycin-type nucleoside antibiotics—have been shown to have potent anti-TB activity by inhibiting bacterial translocase I, a ubiquitous and essential enzyme that functions in peptidoglycan biosynthesis. The present review discusses current literature concerning the biosynthesis and chemical synthesis of capuramycin and analogs, seeking to highlight the potential of the capuramycin scaffold as a favorable anti-TB therapeutic that warrants further development.