文献类型：期刊文献

英文题名：A CRISPR-Cas12a-derived biosensing platform for the highly sensitive detection of diverse small molecules

作者：Liang, Mindong[1,2,3];Li, Zilong[4,5];Wang, Weishan[4,5];Liu, Jiakun[1,2,6];Liu, Leshi[1,2];Zhu, Guoliang[1,2];Karthik, Loganathan[1,2];Wang, Man[7];Wang, Ke-Feng[1,2];Wang, Zhong[8];Yu, Jing[9];Shuai, Yuting[1,2];Yu, Jiaming[1,2];Zhang, Lu[1,2];Yang, Zhiheng[1,2];Li, Chuan[1,2];Zhang, Qian[1,2];Shi, Tong[1,2];Zhou, Liming[1,2];Xie, Feng[4,5];Dai, Huanqin[4,5];Liu, Xueting[1,2];Zhang, Jingyu[1,2];Liu, Guang[1,2];Zhuo, Ying[1,2];Zhang, Buchang[3];Liu, Chenli[6];Li, Shanshan[10];Xia, Xuekui[11];Tong, Yaojun[12];Liu, Yanwen[13];Alterovitz, Gil[14];Tan, Gao-Yi[1,2];Zhang, Li-Xin[1,2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Biotechnol, Shanghai 200237, Peoples R China;[3]Anhui Univ, Inst Phys Sci & Informat Technol, Hefei 230601, Anhui, Peoples R China;[4]Chinese Acad Sci, State Key Lab Microbiol Resources, Inst Microbiol, Beijing 100101, Peoples R China;[5]Chinese Acad Sci, CAS Key Lab Pathogen Microbiol & Immunol, Inst Microbiol, Beijing 100101, Peoples R China;[6]Chinese Acad Sci, Shenzhen Inst Synthet Biol, Shenzhen Inst Adv Technol, Shenzhen 518055, Peoples R China;[7]Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai 200240, Peoples R China;[8]Shanghai Jiao Tong Univ, Dept Urol, Peoples Hosp 6, South Campus, Shanghai 201499, Peoples R China;[9]Shanghai Jiao Tong Univ, Dept Clin Lab, Peoples Hosp 6, South Campus, Shanghai 201499, Peoples R China;[10]Chinese Acad Agr Sci, State Key Lab Biol Plant Dis & Insect Pests, Inst Plant Protect, Beijing 100193, Peoples R China;[11]Qilu Univ Technol, Key Biosensor Lab Shandong Prov, Biol Inst, Shandong Acad Sci, Jinan 250013, Shandong, Peoples R China;[12]Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2800 Lyngby, Denmark;[13]InBiome Sci, 3403 SW 86th ST, Gainesville, FL 32608 USA;[14]Harvard Med Sch, Countway Lib, 10 Shattuck St, Boston, MA 02115 USA

年份：2019

卷号：10

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000480683300002)】；

基金：The authors would like to thank Xian'en Zhang, Jianguo Shi, Huarong Tan, Changheng Liu, Pinghua Liu, Yihua Chen, Minyong Li, Linquan Bai, Jian-Jiang Zhong, Tiangang Liu and Shi Chen for helpful discussions. This work was supported by the National Natural Science Foundation of China [31430002, 31720103901, 31870040, 21877038], the "111" Project of China [B18022], the Fundamental Research Funds for the Central Universities [22221818014], the China Postdoctoral Science Foundation [2018M643243], the Natural Science Foundation from Shandong Province [ZR2017ZB0206], and the Shandong Taishan Scholar Award to Lixin Zhang.

语种：英文

摘要：Besides genome editing, CRISPR-Cas12a has recently been used for DNA detection applications with attomolar sensitivity but, to our knowledge, it has not been used for the detection of small molecules. Bacterial allosteric transcription factors (aTFs) have evolved to sense and respond sensitively to a variety of small molecules to benefit bacterial survival. By combining the single-stranded DNA cleavage ability of CRISPR-Cas12a and the competitive binding activities of aTFs for small molecules and double-stranded DNA, here we develop a simple, supersensitive, fast and high-throughput platform for the detection of small molecules, designated CaT-SMelor (CRISPR-Cas12a-and aTF-mediated small molecule detector). CaT-SMelor is successfully evaluated by detecting nanomolar levels of various small molecules, including uric acid and p-hydroxybenzoic acid among their structurally similar analogues. We also demonstrate that our CaT-SMelor directly measured the uric acid concentration in clinical human blood samples, indicating a great potential of CaT-SMelor in the detection of small molecules.