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Silencing cryptic specialized metabolism in Streptomyces by the nucleoid-associated protein Lsr2

Emma J. Gehrke, Xiafei Zhang, Sheila M. Pimentel-Elardo, Andrew R. Johnson, Christiaan A. Rees, Stephanie E. Jones, Hindra, Sebastian S. Gehrke, Sonya Turvey, Suzanne Boursalie, Jane E. Hill, Erin E. Carlson, Justin R. Nodwell, View ORCID ProfileMarie A. Elliot
doi: https://doi.org/10.1101/614727
Emma J. Gehrke
1Department of Biology, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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Xiafei Zhang
1Department of Biology, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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Sheila M. Pimentel-Elardo
3Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
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Andrew R. Johnson
4Department of Chemistry, Indiana University, Bloomington, Indiana, USA
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Christiaan A. Rees
6Geisel School of Medicine and Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA
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Stephanie E. Jones
1Department of Biology, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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Hindra
1Department of Biology, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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Sebastian S. Gehrke
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
5Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario Canada
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Sonya Turvey
1Department of Biology, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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Suzanne Boursalie
1Department of Biology, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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Jane E. Hill
6Geisel School of Medicine and Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA
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Erin E. Carlson
4Department of Chemistry, Indiana University, Bloomington, Indiana, USA
7Department of Chemistry, University of Minnesota, Minneapolis, Minnesota, USA
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Justin R. Nodwell
3Department of Biochemistry, University of Toronto, Toronto, Ontario, Canada
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Marie A. Elliot
1Department of Biology, McMaster University, Hamilton, Ontario, Canada
2Michael G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada
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  • ORCID record for Marie A. Elliot
  • For correspondence: melliot@mcmaster.ca
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ABSTRACT

Lsr2 is a nucleoid-associated protein conserved throughout the actinobacteria, including the antibiotic-producing Streptomyces. Streptomyces species 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 protect Streptomyces from the inappropriate expression of specialized metabolites, and provide global control over Streptomyces’ arsenal of signalling and antagonistic compounds.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 22, 2019.
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Silencing cryptic specialized metabolism in Streptomyces by the nucleoid-associated protein Lsr2
Emma J. Gehrke, Xiafei Zhang, Sheila M. Pimentel-Elardo, Andrew R. Johnson, Christiaan A. Rees, Stephanie E. Jones, Hindra, Sebastian S. Gehrke, Sonya Turvey, Suzanne Boursalie, Jane E. Hill, Erin E. Carlson, Justin R. Nodwell, Marie A. Elliot
bioRxiv 614727; doi: https://doi.org/10.1101/614727
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Silencing cryptic specialized metabolism in Streptomyces by the nucleoid-associated protein Lsr2
Emma J. Gehrke, Xiafei Zhang, Sheila M. Pimentel-Elardo, Andrew R. Johnson, Christiaan A. Rees, Stephanie E. Jones, Hindra, Sebastian S. Gehrke, Sonya Turvey, Suzanne Boursalie, Jane E. Hill, Erin E. Carlson, Justin R. Nodwell, Marie A. Elliot
bioRxiv 614727; doi: https://doi.org/10.1101/614727

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