Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces
文献类型：期刊论文
| 作者 | Zhou, Qun5,6,7; Zhao, Yatong5,6,7; Ke, Changqiang4 ; Wang, Haojun3; Gao, Sheng3; Li, Hui3; Zhang, Yan2,6,7; Ye, Yang4; Luo, Yunzi1,5,6,7
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| 刊名 | NATURE COMMUNICATIONS
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| 出版日期 | 2024-11-13 |
| 卷号 | 15期号:1页码:12 |
| DOI | 10.1038/s41467-024-54196-z |
| 英文摘要 | The multifunctional proteins of class 2 CRISPR systems such as Cas9, have been employed to activate cryptic biosynthetic gene clusters (BGCs) in Streptomyces, which represent a large and hidden reservoir of natural products. However, such approaches are not applicable to most Streptomyces strains with reasons to be comprehended. Inspired by the prevalence of the class 1 subtype especially the type I-E CRISPR system in Streptomyces, here we report the development of the type I-E CRISPR system into a series of transcriptional regulation tools. We further demonstrate the effectiveness of such activators in nine phylogenetically distant Streptomyces strains. Using these tools, we successfully activate 13 out of 21 BGCs and lead to the identification and characterization of one polyketide, one Ripp and three alkaloid products. Our work is expected to have a profound impact and to facilitate the discovery of numerous structurally diverse compounds from Streptomyces. Streptomyces natural product exploration is impeded by the paucity of genetic editing tools available. Here, the authors engineer endogenous type I-E CRISPR into a series of transcriptional regulation tools for activation of cryptic BGCs from the non-model Streptomyces strains. |
| WOS关键词 | ESCHERICHIA-COLI ; RNA-POLYMERASE ; GENE ; BIOSYNTHESIS ; ACTINORHODIN ; DNA ; ACTIVATION ; EXPRESSION ; PROTEIN ; CLONING |
| 资助项目 | This work was supported by the National Natural Science Foundation of China (32471492, 32071426), the National Key Research and Development Program of China (2018YFA0903300), the Haihe Laboratory of Sustainable Chemical Transformations for financial suppor[32471492] ; This work was supported by the National Natural Science Foundation of China (32471492, 32071426), the National Key Research and Development Program of China (2018YFA0903300), the Haihe Laboratory of Sustainable Chemical Transformations for financial suppor[32071426] ; National Natural Science Foundation of China[2018YFA0903300] ; National Key Research and Development Program of China[24HHWCSS00006] ; Haihe Laboratory of Sustainable Chemical Transformations[2020B0303070002] ; Key-Area Research and Development Program of Guangdong Province |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001354505000021 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315971]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Ye, Yang; Luo, Yunzi |
| 作者单位 | 1.Tianjin Univ, Georgia Tech Shenzhen Inst, Tangxing Rd 133, Shenzhen, Peoples R China 2.Tianjin Univ, Sch Pharmaceut Sci & Technol, New Cornerstone Sci Lab, Tianjin, Peoples R China 3.Sichuan Univ, West China Hosp, Dept Gastroenterol, State Key Lab Biotherapy, Chengdu 610041, Sichuan, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 5.Haihe Lab Sustainable Chem Transformat, Tianjin, Peoples R China 6.Tianjin Univ, Sch Chem Engn & Technol, Key Lab Syst Bioengn, Minist Educ, Tianjin, Peoples R China 7.Tianjin Univ, Frontiers Sci Ctr Synthet Biol, Sch Chem Engn & Technol, Minist Educ, Tianjin, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Qun,Zhao, Yatong,Ke, Changqiang,et al. Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces[J]. NATURE COMMUNICATIONS,2024,15(1):12. |
| APA | Zhou, Qun.,Zhao, Yatong.,Ke, Changqiang.,Wang, Haojun.,Gao, Sheng.,...&Luo, Yunzi.(2024).Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces.NATURE COMMUNICATIONS,15(1),12. |
| MLA | Zhou, Qun,et al."Repurposing endogenous type I-E CRISPR-Cas systems for natural product discovery in Streptomyces".NATURE COMMUNICATIONS 15.1(2024):12. |
入库方式： OAI收割
来源：上海药物研究所
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