Ribosomal Protein S12 and Its Effects on Specialized Metabolism of Streptomyces Bacteria

Species within the actinobacterial genus Streptomyces represent one of the most gifted natural chemists in the microbial world. Their specialized metabolites attract the interest of the pharmaceutical industry as a source of novel drugs. A majority of these molecules pose an insurmountable challenge for economically justified production via chemical synthesis. Therefore, submerged fermentation-based isolation of such molecules often remains the only viable way to obtain them. This in turn fuels interest in process development programs aiming to maximize the yield of specialized metabolite per volume unit of fermentation medium. Along with the optimization of the medium and the fermentation mode itself, strain improvement remains an important part of an overall process development endeavor. An improved strain can be generated via application of traditional approaches of selection for random or induced mutants and genomics-enabled genetic engineering methods. Here I focus on a specific class of mutations with the gene rpsL for ribosomal protein S12, which often confer resistance to streptomycin in bacteria and upregulate specialized metabolism in Streptomyces. The review will portray the evolution of our understanding of the mechanisms behind rpsL mutations, as well as how technological advances change the way these mutations are introduced into the genomes of interest.