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

被引：240

作者：

Zhang, Mingzi M. ^{[1
]}

Wong, Fong Tian ^{[2
]}

Wang, Yajie ^{[3
]}

Luo, Shangwen ^{[3
]}

Lim, Yee Hwee ^{[4
]}

Heng, Elena ^{[2
]}

Yeo, Wan Lin ^{[1
]}

Cobb, Ryan E. ^{[3
]}

Enghiad, Behnam ^{[3
]}

Ang, Ee Lui ^{[1
]}

Zhao, Huimin ^{[1
,3
]}

机构：

[1] Agcy Sci Technol & Res, Metab Engn Res Lab, Sci & Engn Inst, Singapore, Singapore

[2] ASTAR, Biomed Sci Inst, Mol Engn Lab, Singapore, Singapore

[3] Univ Illinois, Dept Chem & Biomol Engn, Urbana, IL USA

[4] ASTAR, Inst Chem & Engn Sci, Organ Chem, Singapore, Singapore

来源：

NATURE CHEMICAL BIOLOGY | 2017年 / 13卷 / 06期

基金：

新加坡国家研究基金会; 美国国家卫生研究院;

关键词：

NATURAL-PRODUCTS; CLONING; IDENTIFICATION; ROSEOSPORUS; EXPRESSION; DISCOVERY; PATHWAY; SYSTEM; ALBUS;

D O I：

10.1038/nchembio.2341

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：607 / U173

页数：5

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