1. Silencing cryptic specialized metabolism in Streptomyces by the nucleoid-associated protein Lsr2
- Author
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Suzanne Boursalie, Sonya Turvey, Christiaan A. Rees, Stephanie Jones, Emma J. Gehrke, Erin E. Carlson, Hindra, Andrew R. Johnson, Jane E. Hill, Marie A. Elliot, Sebastian S. Gehrke, Sheila M. Pimentel-Elardo, Justin R. Nodwell, and Xiafei Zhang
- Subjects
0301 basic medicine ,QH301-705.5 ,Science ,030106 microbiology ,Repressor ,DNA-binding protein ,Streptomyces ,antibiotics ,General Biochemistry, Genetics and Molecular Biology ,Actinobacteria ,03 medical and health sciences ,Gene expression ,specialized metabolism ,Nucleoid ,Gene silencing ,Biology (General) ,Psychological repression ,030304 developmental biology ,Genetics ,0303 health sciences ,repressor ,General Immunology and Microbiology ,biology ,030306 microbiology ,General Neuroscience ,Wild type ,Chromosome ,General Medicine ,biology.organism_classification ,nucleoid-associated protein ,030104 developmental biology ,Medicine - Abstract
Lsr2 is a nucleoid-associated protein conserved throughout the actinobacteria, including the antibiotic-producingStreptomyces.Streptomycesspecies encode paralogous Lsr2 proteins (Lsr2 and Lsr2-like, or LsrL), and we show here that of the two, Lsr2 has greater functional significance. We found that Lsr2 binds AT-rich sequences throughout the chromosome, and broadly represses gene expression. Strikingly, specialized metabolic clusters were over-represented amongst its targets, and the cryptic nature of many of these clusters appears to stem from Lsr2-mediated repression. Manipulating Lsr2 activity in model species and uncharacterized isolates resulted in the production of new metabolites not seen in wild type strains. Our results suggest that the transcriptional silencing of biosynthetic clusters by Lsr2 may protectStreptomycesfrom the inappropriate expression of specialized metabolites, and provide global control overStreptomyces’arsenal of signalling and antagonistic compounds.
- Published
- 2019
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