Activating natural product synthesis using CRISPR interference and activation systems in Streptomyces

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dc.contributor.orgDepartment of Biosciencesen_US
dc.creatorAmeruoso, Andreaen_US
dc.date.accessioned2021-10-27T14:01:41Zen_US
dc.date.available2021-10-27T14:01:41Zen_US
dc.date.issued10/27/2021en_US
dc.description.abstractThe rise of antibiotic-resistant bacteria represents a major threat to global health, creating an urgent need to discover new antibiotics. Natural products derived from the genus Streptomyces represent a rich and diverse repertoire of chemical molecules from which new antibiotics are likely to be found. However, a major challenge is that the biosynthetic gene clusters (BGCs) responsible for natural product synthesis are often poorly expressed under laboratory culturing conditions, thus preventing isolation and screening of novel chemicals. To address this, we describe a novel approach to activate silent BGCs through rewiring endogenous regulation using synthetic gene regulators based upon CRISPR-Cas. First, we create CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) systems that allow for highly programmable and effective gene repression and activation in Streptomyces. We then harness these tools to activate a silent BGC through perturbing its endogenous regulatory network. Together, this work advances the synthetic regulatory toolbox for Streptomyces and facilitates the programmable activation of silent BGCs for novel chemical discovery.en_US
dc.format.mimetypeapplication/vnd.openxmlformats-officedocument.spreadsheetml.sheeten_US
dc.identifier.citationAmeruoso, Andrea (2021): Activating natural product synthesis using CRISPR interference and activation systems in Streptomyces. [Dataset]. Rice University. https://doi.org/10.25611/5SAC-CW45en_US
dc.identifier.doihttps://doi.org/10.25611/5SAC-CW45en_US
dc.identifier.urihttps://hdl.handle.net/1911/111612en_US
dc.language.isoengen_US
dc.publisherRice Universityen_US
dc.rightsCC0 1.0 Universalen_US
dc.rights.urihttps://creativecommons.org/publicdomain/zero/1.0/en_US
dc.subject.keywordstreptomycesen_US
dc.subject.keywordbiosynthetic gene clustersen_US
dc.subject.keywordCRISPRien_US
dc.subject.keywordCRISPRaen_US
dc.subject.keywordnatural productsen_US
dc.titleActivating natural product synthesis using CRISPR interference and activation systems in Streptomycesen_US
dc.title.subtitleDataseten_US
dc.type.dcmiDataseten_US
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