One-shot NMR analysis of microbial secretions identifies highly potent proteasome inhibitor.

ABSTRACT: Natural products represent valuable lead structures for drug discovery. However, for most bioactive compounds no cellular target is yet identified and many substances predicted from genome analysis are inaccessible due to their life stage-dependent biosynthesis, which is not reflected in common isolation procedures. In response to these issues, an NMR-based and target-directed protease assay for inhibitor detection of the proteasome was developed. The methodology is suitable for one-shot identification of inhibitors in conglomerates and crude culture broths. The technique was applied for analysis of the different life stages of the bacterium Photorhabdus luminescens, which resulted in the isolation and characterization of cepafungin I (CepI), the strongest proteasome inhibitor described to

SUBMITTER: Stein ML 

PROVIDER: S-EPMC3494908 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature