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CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters.

ABSTRACT: Here we report an efficient CRISPR-Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover new compounds with interesting bioactivities.

SUBMITTER: Zhang MM 

PROVIDER: S-EPMC5634907 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters.

Zhang Mingzi M MM   Wong Fong Tian FT   Wang Yajie Y   Luo Shangwen S   Lim Yee Hwee YH   Heng Elena E   Yeo Wan Lin WL   Cobb Ryan E RE   Enghiad Behnam B   Ang Ee Lui EL   Zhao Huimin H  

Nature chemical biology 20170410

Here we report an efficient CRISPR-Cas9 knock-in strategy to activate silent biosynthetic gene clusters (BGCs) in streptomycetes. We applied this one-step strategy to activate multiple BGCs of different classes in five Streptomyces species and triggered the production of unique metabolites, including a novel pentangular type II polyketide in Streptomyces viridochromogenes. This potentially scalable strategy complements existing activation approaches and facilitates discovery efforts to uncover n  ...[more]

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