Streptomyces, soil dwelling bacteria, have provided more than half of the antibiotics currently in use, but the rate of discovery of novel bioactive compounds is declining. Rapid genome sequencing, however, has led to the identification of numerous cryptic pathways that may encode novel metabolites for human therapeutics. Sadly enough, most genes holding this enormous biosynthetic potential appear to be silent under typical laboratory conditions. Hereby, we propose to hunt those cryptic gene clusters through gene mining approaches and wake them up in different experimental set-ups, in particularly by so-called Reporter Guided Mutant selection. Structure elucidation of the newly identified compounds will be done by MS and NMR spectroscopy, while bioactivity will be checked through available techniques. Thus, the project revolves round targeted activation of cryptic / silent gene clusters and production of associated novel metabolites which will enable us to combat the challenges posed by resistant pathogens.
Updated: April 2017