Bioassay guided fractionation of this extract led to the isolation of the novel antibiotic platencin, which is a potent and selective inhibitor of FabF. The novel structure of platencin was elucidated by NMR as a tetracyclic ketolide connected to 3-amino-2, 4-dihydroxy benzoic acid via a two carbon chain through an amide bond. Platencin exhibits a broad spectrum Gram-positive antibacterial activity through inhibition of fatty acid biosynthesis. It does not exhibit cross-resistance to key antibiotic resistant strains tested, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus and vancomycin-resistant Enterococci. Platencin shows potent in vivo efficacy without any observed toxicity. It targets two essential proteins, beta-ketoacyl-[acyl-carrier-protein (ACP)] synthase II (FabF), and III (FabH) with IC₅₀ values of 1.95 and 3.91 µg/ml respectively. Platencin is structurally related to platensimycin, another antibiotic isolated from Streptomyces platensis. However, platensimycin only targets FabF (IC₅₀ 0.13 µg/ml) in S. aureus, emphasizing the fact that more antibiotics with novel structures and new modes of action can be discovered utilizing this novel antisense differential sensitivity whole-cell screening paradigm. Isolation, structure and activity of platencin will be described.