A widespread bacterial phenazine forms S-conjugates with biogenic thiols and crosslinks proteins

摘要: Phenazines are redox-active compounds produced by a range of bacteria, including many pathogens. Endowed with various biological activities, these ubiquitous N-heterocycles well known for their ability to generate reactive oxygen species redox cycling. may lead an irreversible depletion glutathione, but detailed mechanism has remained elusive. Furthermore, it is not understood why phenazines have so protein targets and cause misfolding as aggregation. Here we report the discovery unprecedented conjugates (panphenazines A, B) panthetheine phenazine-1-carboxylic (PCA) acid from Kitasatospora sp., which prompted us investigate biogenesis. We found that PCA reacts diverse biogenic thiols under radical-forming conditions, provides plausible model glutathione depletion. To evaluate scope reaction in cells designed biotin rhodamine labelling examined covalent fusion proteins (ketosynthase, carbonic anhydrase III, albumin). Our results reveal important, yet overlooked roles show first time function conjugation crosslinking.