Platensimycin, Streptomyces sp.

A cell-permeable Streptomyces-derived antibiotic that exhibits broad-spectrum Gram-positive antibacterial activity by selectively targeting the elongation condensing enzyme FabF (IC₅₀ = 48 and 160 nM against S. aureus and E. coli FabF, respectively), but not the initiation condensing enzyme FabH (IC₅₀ = 67 µM), involved in type II fatty acid synthesis (FASII). Binding studies indicate that acyl-FabF intermediate complex formation induces a FabF conformation change that is necessary for Platensimycin interaction. Platensimycin effectively kills numerous Staphylococcus aureus, Enterococcus faecium, and Streptococcus pneumoniae strains, including the ones that are resistant to methicillin and vancomycin (Cat. No. 627850). Platensimycin does not exhibit antifungal activity towards Candida albicans (no effect at 64 µg/ml) or toxicity toward mammalian HeLa culture (no effect at 1000 µg/ml) and is efficacious in treating S. aureus infection in mice in vivo (~10⁵-fold bacteria titre reduction via a 24 h i.v. at 150 µg h^-1). Although Platensimycin is ineffective toward wild-type E. coli due to the presence of functional multidrug efflux pump (no effect at 64 µg/ml), Platensimycin does inhibit the growth of efflux-negative E. coli strains.

A cell-permeable Streptomyces-derived antibiotic that exhibits broad-spectrum Gram-positive antibacterial activity by selectively targeting the elongation condensing enzyme FabF (IC₅₀ = 48 and 160 nM against S. aureus and E. coli FabF, respectively), but not the initiation condensing enzyme FabH (IC₅₀ = 67 µM), involved in type II fatty acid synthesis (FASII). Binding studies indicate that acyl-FabF intermediate complex formation induces a FabF conformation change that is necessary for Platensimycin interaction. Platensimycin effectively kills numerous Staphylococcus aureus, Enterococcus faecium, and Streptococcus pneumoniae strains, including the ones that are resistant to methicillin and vancomycin (Cat. No. 627850). Platensimycin does not exhibit antifungal activity towards Candida albicans (no effect at 64 µg/ml) or toxicity toward mammalian HeLa culture (no effect at 1000 µg/ml) and is efficacious in treating S. aureus infection in mice in vivo (~10⁵-fold bacteria titre reduction via a 24 h i.v. at 150 µg h^-1). Although Platensimycin is ineffective toward wild-type E. coli due to the presence of functional multidrug efflux pump (no effect at 64 µg/ml), Platensimycin does inhibit the growth of efflux-negative E. coli strains. Platensimycin has been shown to potently and selectively inhibit hepatocyte FAS and fatty acid oxidation (FAO), without affecting sterol synthesis. Platensimycin is also known as Fatty Acid Synthase Inhibitor III.

Toxicity: Harmful (C)

Wu, M., et al. 2011. Proc. Natl. Acad. Sci. USAin press.
Wang, J., et al. 2007. Proc. Natl. Acad. Sci. USA104, 7612.
Singh, S.B., et al. 2006. J. Am. Chem. Soc.128, 11916.
Wang, J., et al. 2006. Nature441, 358.

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