In silico analysis of regulatory elements of the bldD gene of antibiotic-producing Streptomyces species

Abstract Background: Streptomyces are known for their ability to produce a great variety of antibiotics and other bioactive compounds. The production of these molecules is temporally and genetically coordinated with the bacterial morphological changes. These changes are controlled by transcriptional regulators which coincide with antibiotics production. The bldD gene is identified as one of the key players in the complex morphogenesis and activator of antibiotic production in Streptomyces. Besides the laboratory-based experimental works, Genome mining and in silico analysis of transcription start sites, promoter regions, transcription factors, and their binding sites, CpG islands of the bldD gene of antibiotic-producing Streptomyces species are the fundamental steps to understanding the regulatory mechanisms and its impact on the antibiotic production. Results: Our study identified the most important promoters in the upstream coding regions of the bldD gene of the 13 antibiotic-producing Streptomyces species. All, 13/13 (100%) of bldD genes have a single transcription start site (TSS) flanking the coding regions. The MEME algorithm revealed five motifs (MtS1-5), of which Motif 1 (MtS1) has the lowest E value and the key regulatory motifs for bldD genes among the discovered motifs. Using the TOMTOM web program, we identified 13 transcription factors with a capacity to bind MtS1. The analysis of the CpG Island of the bldD gene of the antibiotic-producing Streptomyces species indicated the presence of lower CpG islands. Phylogenetic analysis identified that bldD genes of antibiotic-producing species considered in this study are very closely related to other groups of Streptomyces. Conclusions Our study showed that the regulatory elements of bldD genes in antibiotic-producing Streptomyces are located closely upstream of the genes. A detailed understanding of these regulatory elements of the gene that encodes the key activator of antibiotic biosynthesis in Streptomyces species will in enhance the laboratory-based experiments for the production of the antibiotic.