ABSTRACT: The gram-positive bacterium, Streptomyces avermitilis holds industrial importance, which produces widely used anthelmintic agent, avermectin. Furthermore, S. avermitilis is generally considered as a prominent heterologous gene expression host for diverse secondary metabolites biosynthesis. However, despite of its industrial importance, it largely remains unknown how its genome is organized and regulated for timely gene expression. Here, we determined 1,601 transcription units (TU) encoded in its genome using the integrated analysis of high-throughput sequencing data including dRNA-Seq, Term-Seq, RNA-Seq, and Ribo-Seq. In addition to TU cataloguing, these information-rich results also revealed the presence of diverse regulatory elements for the transcriptional and translational control of individual TU, such as promoters, 5¢-UTRs, terminators, 3¢-UTRs, and riboswitches. The conserved promoter sequences for transcription initiation were identified from 2,361 transcription start sites as 5¢-TANNNT and 5¢-TGAC for -10 and -35 elements, respectively. Interestingly, the -35 element and spacer length between them were critical for transcriptional regulation of functionally distinct genes. Total 2,017 transcription termination sites were detected from Term-Seq analysis, revealing that stem structure formation is a prerequisite for transcription termination and that Rho-independent termination prevails in S. avermitilis. Lastly, the TU architecture suggests the presence of novel small RNAs and cis-regulatory elements in the genome. Our findings will serve as invaluable resources for comprehensive understanding on regulatory features of S. avermitilis. Moreover, it is anticipated the elevation of its potential as the heterologous expression host for diverse secondary metabolite biosynthesis.
