Abstract
Bacteria belonging to Streptomyces have the ability to produce a wide range of secondary metabolites through a shift from primary to secondary metabolism regulated by complex networks activated after vegetative growth terminates. Despite considerable effort to understand the regulatory elements governing gene expression related to primary and secondary metabolism in Streptomyces, system-level information remains limited. In this study, we integrated four multi-omics datasets from Streptomyces griseus NBRC 13350: RNA-seq, ribosome profiling, dRNA-seq, and Term-Seq, to analyze the regulatory elements of transcription and translation of differentially expressed genes during cell growth. With the functional enrichment of gene expression in different growth phases, one sigma factor regulon and four transcription factor regulons governing differential gene transcription patterns were found. In addition, the regulatory elements of transcription termination and post-transcriptional processing at transcript 3′-end positions were elucidated, including their conserved motifs, stem-loop RNA structures, and non-terminal locations within the polycistronic operons, and the potential regulatory elements of translation initiation and elongation such as 5′-UTR length, RNA structures at ribosome-bound sites, and codon usage were investigated. This comprehensive genetic information provides a foundational genetic resource for strain engineering to enhance secondary metabolite production in Streptomyces.
Highlights
Streptomyces is a rich source of various secondary metabolites that exhibit a broad range of bioactivities, such as antimicrobial, antifungal, and anticancer (Worthen, 2008; Craney et al, 2013)
A-factor biosynthesis was predicted to be already activated in the E phase, we found genes afsA and bprA in groups VII (N-U) and IX (N-N), respectively
This study systematically analyzed the regulatory elements of transcription and translation levels affecting differentially expressed genes (DEGs) in Streptomyces griseus NBRC 13350 during their growth and functional enrichments (Figure 8)
Summary
Streptomyces is a rich source of various secondary metabolites that exhibit a broad range of bioactivities, such as antimicrobial, antifungal, and anticancer (Worthen, 2008; Craney et al, 2013). Regulatory Elements of Streptomyces griseus activated after vegetative growth terminates through a metabolic shift from primary to secondary metabolism, accompanied by morphological differentiation (Alam et al, 2010). This is because 1) both sporulation and secondary metabolism are needed to survive competition with other microorganisms under limited nutrient conditions (Hodgson, 2000; Van Wezel and Mcdowall, 2011), 2) the primary metabolites should be accumulated to obtain sufficient concentration as precursors of the secondary metabolites (Zabala et al, 2013), and 3) the production of secondary metabolites requires a lot of nutrients and energy, such as ATP and NAD(P)H, which can be used for growth (Komatsu et al, 2010). Several translational regulations have been reported in Streptomyces, such as ppGpp (Hesketh et al, 2007) and BldA., which is a unique tRNA for the rare codon TTA leucine (Higo et al, 2011; Hackl and Bechthold, 2015)
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