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

共 27 条

[1] High-yield actinorhodin production in fed-batch culture by a Streptomyces lividans strain overexpressing the pathway-specific activator gene actII-ORF4 [J].

Bruheim, P ;

Sletta, H ;

Bibb, MJ ;

White, J ;

Levine, DW .

JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY, 2002, 28 (02) :103-111

[2] High-Efficiency Multiplex Genome Editing of Streptomyces Species Using an Engineered CRISPR/Cas System [J].

Cobb, Ryan E. ;

Wang, Yajie ;

Zhao, Huimin .

ACS SYNTHETIC BIOLOGY, 2015, 4 (06) :723-728

[3] Direct cloning of large genomic sequences [J].

Cobb, Ryan E. ;

Zhao, Huimin .

NATURE BIOTECHNOLOGY, 2012, 30 (05) :405-406

[4] The new frontier of genome engineering with CRISPR-Cas9 [J].

Doudna, Jennifer A. ;

Charpentier, Emmanuelle .

SCIENCE, 2014, 346 (6213) :1077-+

[5] Cloning, expression, and biochemical characterization of streptomyces rubellomurinus genes required for biosynthesis of antimalarial compound FR900098 [J].

Eliot, Andrew C. ;

Griffin, Benjamin M. ;

Thomas, Paul M. ;

Johannes, Tyler W. ;

Kelleher, Neil L. ;

Zhao, Huimin ;

Metcalf, William W. .

CHEMISTRY & BIOLOGY, 2008, 15 (08) :765-770

[6] Evolution of chemical diversity by coordinated gene swaps in type II polyketide gene clusters [J].

Hillenmeyer, Maureen E. ;

Vandova, Gergana A. ;

Berlew, Erin E. ;

Charkoudian, Louise K. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (45) :13952-13957

[7] One-step high-efficiency CRISPR/Cas9-mediated genome editing in Streptomyces [J].

Huang, He ;

Zheng, Guosong ;

Jiang, Weihong ;

Hu, Haifeng ;

Lu, Yinhua .

ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2015, 47 (04) :231-243

[8] Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs [J].

Jomaa, H ;

Wiesner, J ;

Sanderbrand, S ;

Altincicek, B ;

Weidemeyer, C ;

Hintz, M ;

Türbachova, I ;

Eberl, M ;

Zeidler, J ;

Lichtenthaler, HK ;

Soldati, D ;

Beck, E .

SCIENCE, 1999, 285 (5433) :1573-1576

[9] Multiplexed CRISPR/Cas9-and TAR-Mediated Promoter Engineering of Natural Product Biosynthetic Gene Clusters in Yeast [J].

Kang, Hahk-Soo ;

Charlop-Powers, Zachary ;

Brady, Sean F. .

ACS SYNTHETIC BIOLOGY, 2016, 5 (09) :1002-1010

[10]

Kieser T., 2000, PRACTICAL STREPTOMYC

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