Adipostatins E-J, New Potent Antimicrobials Identified as Inhibitors of Coenzyme-A Biosynthesis.

ABSTRACT: Phosphopantetheine is a key structural element in biological acyl transfer reactions found embedded within coenzyme A (CoA). Phosphopantothenoylcysteine synthetase (PPCS) is responsible for installing a cysteamine group within phosphopantetheine. Therefore, it holds considerable potential as a drug target for developing new antimicrobials. In this study, we adapted a biochemical assay specific for bacterial PPCS to screen for inhibitors of CoA biosynthesis against a library of marine microbial derived natural product extracts (NPEs). Analysis of the NPE derived from Streptomyces blancoensis led to the isolation of novel antibiotics (10-12, and 14) from the adipostatin class of molecules. The most potent molecule (10) displayed in vitro activity with IC50= 0.93 μM, against S. pneumoniae PPC

SUBMITTER: Gomez-Rodriguez L 

PROVIDER: S-EPMC7453842 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature