platensimycin

Platensimycin (PTM) is an antibiotic produced by S. platensis that inhibits Gram-positve bacteria by selectively inhibiting cellular lipid biosynthesis (IC50 = 0.1 μM). It targets the β-ketoacyl-acyl-carrier-protein synthase I/II, FabF/B, an enzyme that participates in the biosynthesis of fatty acids (IC50s = 48 and 160 nM for S. aureus and E. coli enzymes, respectively). By specifically targeting fatty acid synthesis in bacteria, PTM is thought to be a promising agent for overcoming antibiotic resistance. PTM is also a selective inhibitor of the mammalian fatty acid synthase and has been shown to reduce liver triglyceride levels and to improve insulin sensitivity in a diabetic mouse model after an oral dose of 30 mg/kg.

Platencin is a natural, broad spectrum Gram-positive antibiotic isolated from S. platensis, which is also the source of platensimycin . Platencin inhibits two key enzymes in bacterial fatty acid synthesis, β-ketoacyl-ACP synthases II and III (FabF and FabH, respectively), unlike platensimycin which only targets FabF. The IC50 values for platencin against FabF and FabH are 1.95 and 3.91 μg ml, respectively. It does not exhibit cross-resistance to antibiotic resistant bacterial strains, including methicillin-resistant S. aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant Enterococci. For these reasons, platencin has potential applications in fighting antibiotic resistant bacteria.