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A Versatile Transcription-Translation in One Approach for Activation of Cryptic Biosynthetic Gene Clusters

文献类型：期刊论文

作者Zhang, Qian3,4; Ren, Jin-Wei2; Wang, Weishan3,4; Zhai, Ji'an1,3; Yang, Jing4; Liu, Ning4; Huang, Ying3,4; Chen, Yihua3,4; Pan, Guohui3,4; Fan, Keqiang4
刊名ACS CHEMICAL BIOLOGY
出版日期2020-09-18
卷号15期号:9页码:2551-2557
ISSN号1554-8929
DOI10.1021/acschembio.0c00581
英文摘要The ever-growing drug resistance problem worldwide highlights the urgency to discover and develop new drugs. Microbial natural products are a prolific source of drugs. Genome sequencing has revealed a tremendous amount of uncharacterized natural product biosynthetic gene clusters (BGCs) encoded within microbial genomes, most of which are cryptic or express at very low levels under standard culture conditions. Therefore, developing effective strategies to awaken these cryptic BGCs is of great interest for natural product discovery. In this study, we designed and validated a Transcription Translation in One (TTO) approach for activation of cryptic BGCs. This approach aims to alter the metabolite profiles of target strains by directly overexpressing exogenous rpsL (encoding ribosomal protein S12) and rpoB (encoding RNA polymerase beta subunit) genes containing beneficial mutations for natural product production using a plug-and-play plasmid system. As a result, this approach bypasses the tedious screening work and overcomes the false positive problem in the traditional ribosome engineering approach. In this work, the TTO approach was successfully applied to activating cryptic BGCs in three Streptomyces strains, leading to the discovery of two aromatic polyketide antibiotics, piloquinone and homopiloquinone. We further identified a single BGC responsible for the biosynthesis of both piloquinone and homopiloquinone, which features an unusual starter unit incorporation step. This powerful strategy can be further exploited for BGC activation in strains even beyond streptomycetes, thus facilitating natural product discovery research in the future.
WOS关键词STREPTOMYCES-COELICOLOR ; ANTIBIOTIC PRODUCTION ; NATURAL-PRODUCTS ; RNA-POLYMERASE ; POLYKETIDE ; MUTATIONS ; RESISTANCE ; DISCOVERY ; BACTERIAL ; PILOQUINONE
资助项目International Partnership Program of Chinese Academy of Sciences[153211KYSB20170014] ; program of China Ocean Mineral Resources RD Association[DY13S-B2-02] ; Senior User Project of RV KEXUE from the Center for Ocean Mega -Science, Chinese Academy of Sciences[KEXUE2019GZOS]
WOS研究方向Biochemistry & Molecular Biology
语种英语
WOS记录号WOS:000574920900024
出版者AMER CHEMICAL SOC
资助机构International Partnership Program of Chinese Academy of Sciences ; program of China Ocean Mineral Resources RD Association ; Senior User Project of RV KEXUE from the Center for Ocean Mega -Science, Chinese Academy of Sciences
源URL[http://ir.idsse.ac.cn/handle/183446/7951]  
专题深海科学研究部_深海生物学研究室_深海微生物活性物质研究组
研究生部
通讯作者Pan, Guohui; Fan, Keqiang
作者单位1.Chinese Acad Sci, Inst Deep Sea Sci & Engn, Sanya 572000, Peoples R China
2.Chinese Acad Sci, Inst Microbiol, State Key Lab Mycol, Beijing 100101, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing 100101, Peoples R China
推荐引用方式
GB/T 7714		 Zhang, Qian,Ren, Jin-Wei,Wang, Weishan,et al. A Versatile Transcription-Translation in One Approach for Activation of Cryptic Biosynthetic Gene Clusters[J]. ACS CHEMICAL BIOLOGY,2020,15(9):2551-2557.
APA Zhang, Qian.,Ren, Jin-Wei.,Wang, Weishan.,Zhai, Ji'an.,Yang, Jing.,...&Fan, Keqiang.(2020).A Versatile Transcription-Translation in One Approach for Activation of Cryptic Biosynthetic Gene Clusters.ACS CHEMICAL BIOLOGY,15(9),2551-2557.
MLA Zhang, Qian,et al."A Versatile Transcription-Translation in One Approach for Activation of Cryptic Biosynthetic Gene Clusters".ACS CHEMICAL BIOLOGY 15.9(2020):2551-2557.

入库方式： OAI收割

来源：深海科学与工程研究所

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