Transcriptional and Translational Landscape of the Model Antibiotic Producer Streptomyces Coelicolor

Individual Streptomyces species have the genetic potential to produce a diverse array of natural products of considerable commercial, medical and veterinary importance. However, the genetic information flow of their unique high G+C genomes by transcription and translation processes remains largely unexplored. In order to harness their full biosynthetic potential, it will be important to develop a detailed understanding of the regulatory networks that orchestrate their diverse metabolism. Here, we reveal extensive translational control of the secondary metabolic genes of the model streptomycete, Streptomyces coelicolor A3(2) through the genome-scale integration of transcriptome and translatome data. Our systematic study determined 3,570 transcription start sites and identified a high proportion (~21%) of leaderless mRNAs and 230 small RNAs; this enabled deduction of promoter architecture on a genome-scale. The comprehensive translational landscape was determined by using massively parallel sequencing of ribosome-protected mRNA fragments (Ribo-seq). Interestingly, our study reveals that the translation efficiency of secondary metabolic genes was negatively correlated with transcription and that several key antibiotic regulatory genes were translationally-induced at transition growth phase. These findings could lead to the design of new approaches to antibiotic discovery and development.