The Chemistry and Biological Activity of Platensimycin

Hospital mortalities from multidrug-resistant bacteria have grown in recent years. Multidrugresistant bacteria are becoming a major public health crisis because the antibiotics that exist today are no longer effective in all cases. Drugs, like vancomycin, which were once last-resort treatments are quickly becoming a first-line defense because the over-prescription of antibiotics is allowing for resistant bacteria to develop rapidly. Additionally, the discovery of new effective classes of pharmaceuticals has diminished dramatically since the 1960s. Inspired by this need for a new pharmaceutical that disrupts the function of a novel target, a Merck research group began high-throughput screening of secondary metabolites against FabF, an enzyme involved in bacterial fatty acid biosynthesis, which led to the isolation of platensimycin (1, Figure 1). Platensimycin, isolated from Streptomyces platensis, represents a new structural class of antibiotics with potent broad-spectrum antibacterial activity against Gram-positive bacterial strains. To date, no cross-resistance has been observed, and this is thought to be due to platensimycin’s unique mechanism of action. Given the magnitude of the threat multidrug-resistant bacteria poses, platensimycin offers a new weapon in the fight against bacterial infections. With a molecular-level understanding of its unique mode of action and the structure/function relationships involved, platensimycin stands to enable the development of new clinically viable antibiotics. O OH OH OH