| Streptomyces bacteria produce the majority of antibiotics for the current pharmaceuticals market. Due to the central role of these bacteria in producing antibiotics, academic and industrial research groups have studied regulatory mechanisms of antibiotic synthesis, generated mutant strains with increased productivity, and developed strategies to generate novel bioactive molecules. In our laboratory, we use DNA microarrays of the model organism, Streptomyces coelicolor, to study the regulation of antibiotic production. Our ultimate goal is to engineer an antibiotic-overproducing bacterial strain.; This proof of concept study applied DNA microarrays to the goal of strain improvement. We simulated stress conditions that cells face in nature and identified conditions that increase the production of antibiotics. We found that stresses such as heat shock, phosphate upshift, and hyper-osmotic shift enhanced production; we then used DNA microarrays to identify gene expression changes during those stresses. We identified a putative antibiotic transporter, actII-ORF2, that plays a crucial role in antibiotic overproduction. Using this information, we have engineered a strain that produces over 34-fold more antibiotic compared to the wildtype strain. |
