clovibactin

Clovibactin (Novo29) is a small molecule antibiotic discovered and developed by NovoBiotic Pharmaceuticals. It was identified from uncultured soil bacteria using the iChip technology. Clovibactin exhibits potent bactericidal activity against a broad spectrum of Gram-positive pathogens, including methicillin-resistant *Staphylococcus aureus* (MRSA), *Mycobacterium tuberculosis*, non-tuberculous mycobacteria, *Bacillus anthracis* (anthrax), and vancomycin-resistant Enterococci (VRE). Its unique mechanism of action involves binding to the pyrophosphate moiety of multiple essential peptidoglycan precursors, such as lipid II, lipid IIIWTA, and undecaprenyl pyrophosphate (C55PP). By sequestering these precursors, clovibactin inhibits bacterial cell wall synthesis and triggers the formation of supramolecular fibrils that further stabilize the binding and disrupt the membrane, leading to rapid cell death without detectable resistance development.