小分子靶标的核糖开关生物传感器研究进展

doi:10.19586/j.2095-2341.2021.0140

生物技术进展 ›› 2022, Vol. 12 ›› Issue (2): 168-175.DOI: 10.19586/j.2095-2341.2021.0140

小分子靶标的核糖开关生物传感器研究进展

吴一凡¹(), 林晟豪², 许文涛¹^,²()

^1.中国农业大学食品科学与营养工程学院，北京 100083
^2.中国农业大学营养与健康系，食品精准营养与质量控制教育部重点实验室，北京 100083

收稿日期:2021-08-05 接受日期:2021-09-03 出版日期:2022-03-25 发布日期:2022-03-25
通讯作者: 许文涛
作者简介:吴一凡 E-mail: Wyf001208@126.com;
基金资助:
山东省重大科技创新工程项目(2019JZZY011014);北京市农业科技项目(PXM2021_014207_000037)

Research Progress of Riboswitch Biosensors for Small Molecule Target

Yifan WU¹(), Shenghao LIN², Wentao XU¹^,²()

^1.College of Food Science and Nutritional Engineering，China Agricultural University，Beijing 100083，China
^2.Key Laboratory of Precision Nutrition and Food Quality，Department of Nutrition and Health，China Agricultural University，Beijing 100083，China

Received:2021-08-05 Accepted:2021-09-03 Online:2022-03-25 Published:2022-03-25
Contact: Wentao XU

摘要/Abstract

摘要：

小分子化合物种类繁多，在众多生化过程中发挥关键作用，具有重要的检测意义与价值,其快速灵敏可视化检测技术的开发是当前的研究热点。基于核糖开关的生物传感器因具有识别特性高、操作简便、成本低等优势，为小分子检测提供了一条新途径。对核糖开关的来源、构成、调控机制、体内外筛选，特别是对基于小分子靶标的核糖开关生物传感器分类进行了介绍，并从核糖开关的筛选、裁剪、理性设计、核糖开关无细胞传感器的应用等几个方向提出了展望，以期为小分子靶标的核糖开关生物传感器的发展和应用提供理论依据。

关键词: 小分子靶标, 核糖开关, 生物传感器, 筛选, 基因表达调控

Abstract:

There are many kinds of small molecule compounds， and play key roles in many biological processes， which has important detection significance and value. The development of its rapid and sensitive visual detection technology is a research hotspot at present. Biosensor based on riboswitch provides a new way for small molecule detection due to its advantages， such as high recognition characteristics， simple operation and low cost. In this paper， the source， composition， regulatory mechanism， in vivo and in vitro screening of riboswitches， especially the classification of riboswitch biosensors based on small molecular targets were introduced， which aimed to provide a theoretical basis for the development and application of small molecule target riboswitch biosensor.

Key words: small molecule target, riboswitch, biosensor, screen, gene expression regulation

中图分类号:

Q522

吴一凡, 林晟豪, 许文涛. 小分子靶标的核糖开关生物传感器研究进展[J]. 生物技术进展, 2022, 12(2): 168-175.

Yifan WU, Shenghao LIN, Wentao XU. Research Progress of Riboswitch Biosensors for Small Molecule Target[J]. Current Biotechnology, 2022, 12(2): 168-175.

图/表 2

参考文献 79

1	胡鹏. 核酸适体在蛋白质和小分子检测中的新方法研究[D]. 湖南:湖南大学, 2010.
2	MACHTEL P, BĄKOWSKA Ż K, ŻYWICKI M. Emerging applications of riboswitches——from antibacterial targets to molecular tools[J]. J. Appl. Genet., 2016,57(4): 531-541.
3	TURNER A P F. Biosensors: sense and sensibility[J]. Chem. Soc. Rev., 2013,42(8): 3184-3196.
4	张泽, 张颖聪, 于洪伟, 等. 生物传感器识别元件的种类及其在临床检验中的研究进展[J]. 临床检验杂志, 2020,38(10): 767-771.
5	YOKOBAYASHI Y. Aptamer-based and aptazyme-based riboswitches in mammalian cells[J]. Curr. Opin. Chem. Biol., 2019,52: 72-78.
6	BLOUIN S, MULHBACHER J, PENEDO J C, et al.. Riboswitches: ancient and promising genetic regulators[J]. ChemBioChem, 2009,10(3): 400-416.
7	BAIRD N J, KULSHINA N, FERRE-D'AMARE A R. Riboswitch function flipping the switch or tuning the dimmer?[J]. RNA Biol., 2010,7(3): 328-332.
8	BREAKER R R. Riboswitches and the RNA World[J/OL]. Cold Spring Harbor Perspect. Biol., 2012,4(2):a3566[2022-02-20]. .
9	GOLD L, BROWN D, HE Y Y, et al.. From oligonucleotide shapes to genomic SELEX: novel biological regulatory loops[J]. Proc. Natl. Acad. Sci. USA, 1997,94(1): 59-64.
10	GOLD L, SINGER B, HE Y Y, et al.. SELEX and the evolution of genomes[J]. Curr. Opin. Genet. Devlop., 1997,7(6): 848-851.
11	GELFAND M S, MIRONOV A A, JOMANTAS J, et al.. A conserved RNA structure element involved in the regulation of bacterial riboflavin synthesis genes[J]. Trends Genet., 1999,15(11): 439-442.
12	WINKLER W, NAHVI A, BREAKER R R. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression[J]. Nature, 2002,419(6910): 952-956.
13	MCCOWN P J, CORBINO K A, STAV S, et al.. Riboswitch diversity and distribution[J]. RNA, 2017,23(7): 995-1011.
14	SUBBAIAH K C V, HEDAYA O, WU J, et al.. Mammalian RNA switches: molecular rheostats in gene regulation, disease, and medicine[J]. Comput. Struct. Biotechnol. J., 2019,17: 1326-1338.
15	MACHTEL P, BAKOWSKA-ZYWICKA K, ZYWICKI M. Emerging applications of riboswitches - from antibacterial targets to molecular tools[J]. J. Appl. Genet., 2016,57(4): 531-541.
16	SCULL C E, DANDPAT S S, ROMERO R A, et al.. Transcriptional riboswitches integrate timescales for bacterial gene expression control[J/OL]. Front. Mol. Biosci., 2021,7(607158):607158[2022-02-20]. .
17	熊莹喆, 曹苑青, 肖玲慧, 等. 基于核糖开关的新型基因表达调控系统的应用[J]. 生物技术通报, 2017,33(2): 41-46.
18	BÉDARD A V, HIEN E D M, LAFONTAINE D A. Riboswitch regulation mechanisms: RNA, metabolites and regulatory proteins[J/OL]. Biochim. Biophys. Acta Gene Regul. Mechan., 2020,1863(3): 194501[2022-02-20]. .
19	BARRICK J E, BREAKER R R. The distributions, mechanisms, and structures of metabolite-binding riboswitches[J/OL]. Genome Biol., 2007,8(11): R239[2022-02-20]. .
20	DOMIN G, FINDEISS S, WACHSMUTH M, et al.. Applicability of a computational design approach for synthetic riboswitches[J]. Nucl. Acids Res., 2017,45(7): 4108-4119.
21	BORUJENI A E, MISHLER D M, WANG J, et al.. Automated physics-based design of synthetic riboswitches from diverse RNA aptamers[J]. Nucl. Acids Res., 2016,44(1): 1-13.
22	ELLINGTON A D, SZOSTAK J W. In vitro selection of RNA molecules that bind specific ligands[J]. Nature, 1990,346(6287): 818-822.
23	WITTMANN A, SUESS B. Engineered riboswitches: expanding researchers' toolbox with synthetic RNA regulators[J]. FEBS Lett., 2012,586(15): 2076-2083.
24	MURATA A, SATO S. In vitro selection of RNA aptamers for a small-molecule dye[M]//OGAWA A. Methods in molecular biology, 2014: 17-28.
25	FINDEISS S, ETZEL M, WILL S, et al.. Design of artificial riboswitches as viosensors[J/OL]. Sensors, 2017,17(19909):1990[2022-02-20]. .
26	REYNOSO C M K, MILLER M A, BINA J E, et al.. Riboswitches for intracellular study of genes involved in Francisella pathogenesis[J/OL]. mBIO, 2012,3(6):e00253-12[2022-02-20]. .
27	WACHSMUTH M, FINDEISS S, WEISSHEIMER N, et al.. De novo design of a synthetic riboswitch that regulates transcription termination[J]. Nucl. Acids Res., 2013,41(4): 2541-2551.
28	HANSON S, BAUER G, FINK B, et al.. Molecular analysis of a synthetic tetracycline-binding riboswitch[J]. RNA, 2005,11(4): 503-511.
29	XIAO H, EDWARDS T E, FERRE-D'AMARE A R. Structural vasis for specific, high-affinity tetracycline binding by an in vitro evolved aptamer and artificial riboswitch[J]. Chem. Biol., 2008,15(10): 1125-1137.
30	WEIGAND J E, SUESS B. Tetracycline aptamer-controlled regulation of pre-mRNA splicing in yeast[J]. Nucl. Acids Res., 2007,35(12): 4179-4185.
31	LINK K H, BREAKER R R. Engineering ligand-responsive gene-control elements: lessons learned from natural riboswitches[J]. Gene Ther., 2009,16(10): 1189-1201.
32	SINHA J, REYES S, GALLIVAN J P. Reprogramming bacteria to seek and destroy an herbicide [J/OL]. Nat. Chem. Biol., 2014,10(3): 239[2022-02-20]..
33	WEIGAND J E, SANCHEZ M, GUNNESCH E, et al.. Screening for engineered neomycin riboswitches that control translation initiation[J]. RNA, 2008,14(1): 89-97.
34	杨会勇, 刁勇, 林俊生, 等. 新型基因表达调控元件——人工核糖开关的构建及筛选[J]. 生物工程学报, 2012,28(2): 134-143.
35	NOMURA Y, YOKOBAYASHI Y. Reengineering a natural riboswitch by dual genetic selection[J/OL]. J. Am. Chem. Soc., 2007,129(45): 13814[2022-02-20]. .
36	LYNCH S A, DESAI S K, SAJJA H K, et al.. A high-throughput screen for synthetic riboswitches reveals mechanistic insights into their function[J]. Chem. Biol., 2007,14(2): 173-184.
37	KIRCHNER M, SCHORPP K, HADIAN K, et al.. An in vivo high-throughput screening for riboswitch ligands using a reverse reporter gene system[J/OL]. Sci. Rep., 2017,7:7732[2021-08-28]. .
38	PARKHEY P, MOHAN S V. Biosensing applications of microbial fuel cell: approach toward miniaturization[M]//MOHAN S V, VARJANI S, PANDEY A. Biomass biofuels biochemicals. 2019:977-997.
39	石亚丽, 袁涛, 任婷婷, 等. 生物传感器在食品安全快速检测中应用研究[J]. 粮食与油脂, 2012,25(2): 5-9.
40	SERGANOV A, NUDLER E. A decade of riboswitches[J]. Cell, 2013,152(1-2): 17-24.
41	FOWLER C C, BROWN E D, LI Y. A FACS-based approach to engineering artificial riboswitches[J]. ChemBioChem, 2008,9(12): 1906-1911.
42	YOU M, LITKE J L, JAFFREY S R. Imaging metabolite dynamics in living cells using a spinach-based riboswitch[J]. Proc. Natl. Acad. Sci. USA, 2015,112(21): E2756-E2765.
43	KELLENBERGER C A, HAMMOND M C. In vitro analysis of riboswitch-spinach aptamer fusions as metabolite-sensing fluorescent biosensors[M]//BURKEAGUERO D H. Methods in Enzymology. 2015:147-172.
44	KELLENBERGER C A, WILSON S C, SALES-LEE J, et al.. RNA-based fluorescent biosensors for live cell imaging of second messengers cyclic di-GMP and cyclic AMP-GMP[J]. J. Am. Chem. Soc., 2013,135(13): 4906-4909.
45	DASGUPTA S, SHELKE S A, LI N, et al.. Spinach RNA aptamer detects lead (Ⅱ) with high selectivity[J]. Chem. Commun., 2015,51(43): 9034-9037.
46	SAVAGE J C, SHINDE P, BACHINGER H P, et al.. A ribose modification of Spinach aptamer accelerates lead(ii) cation association in vitro[J]. Chem. Commun., 2019,55(42): 5882-5885.
47	FILONOV G S, MOON J D, SVENSEN N, et al.. Broccoli: rapid selection of an RNA mimic of green fluorescent protein by fluorescence-based selection and directed evolution[J]. J. Am. Chem. Soc., 2014,136(46): 16299-16308.
48	DOLGOSHEINA E V, JENG S C Y, PANCHAPAKESAN S S S, et al.. RNA mango aptamer-fluorophore: a bright, high-affinity complex for RNA labeling and tracking[J]. ACS Chem. Biol., 2014,9(10): 2412-2420.
49	MURANAKA N, SHARMA V, NOMURA Y, et al.. An efficient platform for genetic selection and screening of gene switches in Escherichia coli [J/OL]. Nucl. Acids. Res., 2009,37(5):e39 [2021-08-28]. .
50	DONOVAN P D, HOLLAND L M, LOMBARDI L, et al.. TPP riboswitch-dependent regulation of an ancient thiamin transporter in Candida[J/OL]. PLoS Genet., 2018,14(5): e1007429[2022-02-20]. .
51	MOLDOVAN M A, PETROVA S A, GELFAND M S. Comparative genomic analysis of fungal TPP-riboswitches[J]. Fungal Genet. Biol., 2018,114: 34-41.
52	CROFT M T, MOULIN M, WEBB M E, et al.. Thiamine biosynthesis in algae is regulated by riboswitches[J]. Proc. Natl. Acad. Sci. USA, 2007,104(52): 20770-20775.
53	SUBKI A, HO C L, ISMAIL N, et al.. Identification and characterisation of thiamine pyrophosphate (TPP) riboswitch in Elaeis guineensis[J/OL]. PLoS ONE, 2020,15(7): e235431[2022-02-20]..
54	BASTET L, TURCOTTE P, WADE J T, et al.. Maestro of regulation: riboswitches orchestrate gene expression at the levels of translation, transcription and mRNA decay[J]. RNA Biol., 2018,15(6): 679-682.
55	AGHDAM E M, SINN M, TARHRIZ V, et al.. TPP riboswitch characterization in Alishewanella tabrizica and Alishewanella aestuarii and comparison with other TPP riboswitches[J]. Microbiol. Res., 2017,195: 71-80.
56	PAVLOVA N, PENCHOVSKY R. Genome-wide bioinformatics analysis of FMN, SAM-I, glmS, TPP, lysine, purine, cobalamin, and SAH riboswitches for their applications as allosteric antibacterial drug targets in human pathogenic bacteria[J]. Exp. Opin. Therap. Targets, 2019,23(7): 631-643.
57	PRICE I R, GRIGG J C, KE A. Common themes and differences in SAM recognition among SAM riboswitches[J]. Biochim. Biophys. Acta Gene Regul. Mechan., 2014,1839(10SI): 931-938.
58	TANG D, DU X, SHI Q, et al.. A SAM-I riboswitch with the ability to sense and respond to uncharged initiator tRNA[J/OL]. Nat. Commun., 2020,11(1):2794 [2021-08-28]. .
59	ST-PIERRE P, SHAW E, JACQUES S, et al.. A structural intermediate pre-organizes the add adenine riboswitch for ligand recognition[J]. Nucl. Acids Res., 2021,49(10): 5891-5904.
60	HU G, LI H, XU S, et al.. Ligand binding mechanism and its relationship with conformational changes in adenine riboswitch[J/OL]. Intern. J. Mol. Sci., 2020,21(6):1926[2022-02-20]. .
61	张蕾. 腺嘌呤核糖开关的去折叠路径的多尺度模拟[D]. 北京:北京工业大学, 2015.
62	凌宝萍. 嘌呤核糖开关和细胞凋亡抑制蛋白与药物作用机制的理论研究[D]. 山东:山东大学, 2010.
63	LEMAY J, DESNOYERS G, BLOUIN S, et al.. Comparative study between transcriptionally-and translationally-acting adenine riboswitches reveals key differences in riboswitch regulatory mechanisms[J/OL]. PLoS Genet., 2011,7(1):e1001278 [2021-08-28]. .
64	PAVLOVA N, KALOUDAS D, PENCHOVSKY R. Riboswitch distribution, structure, and function in bacteria[J]. Gene, 2019,708: 38-48.
65	SERGANOV A, YUAN Y R, PIKOVSKAYA O, et al.. Structural basis for discriminative regulation of gene expression by adenine- and guanine-sensing mRNAs[J]. Chem. Biol., 2004,11(12): 1729-1741.
66	KIM J N, BLOUNT K F, PUSKARZ I, et al.. Design and antimicrobial action of purine analogues that bind guanine riboswitches[J]. ACS Chem. Biol., 2009,4(11): 915-927.
67	YAN L H, LE ROUX A, BOYAPELLY K, et al.. Purine analogs targeting the guanine riboswitch as potential antibiotics against Clostridioides difficile [J]. Eur. J. Med. Chem., 2018,143: 755-768.
68	SERGANOV A, HUANG L, PATEL D J. Structural insights into amino acid binding and gene control by a lysine riboswitch[J]. Nature, 2008,455(7217): 1263-1276.
69	MUKHERJEE S, BARASH D, SENGUPTA S. Comparative genomics and phylogenomic analyses of lysine riboswitch distributions in bacteria[J/OL]. PLoS ONE, 2017,12(9):e0184314[2021-08-28]. .
70	ZHOU D, WANG Q, QI Q. Research progress in glmS riboswitch[J]. Acta Microbiol. Sin., 2017,57(8): 1152-1159.
71	MCCOWN P J, ROTH A, BREAKER R R. An expanded collection and refined consensus model of glmS ribozymes[J]. RNA, 2011,17(4): 728-736.
72	LUENSE C E, SCHMIDT M S, WITTMANN V, et al.. Carba-sugars activate the glmS-riboswitch of Staphylococcus aureus [J]. ACS Chem. Biol., 2011,6(7): 675-678.
73	KHAN M A, GOPEL Y, MILEWSKI S, et al.. Two small RNAs conserved in enterobacteriaceae provide intrinsic resistance to antibiotics targeting the cell wall biosynthesis enzyme glucosamine-6-phosphate synthase[J/OL]. Front. Microbiol., 2016,7:908[2021-08-28]. .
74	FINNEY L A, O'HALLORAN T V. Transition metal speciation in the cell: Insights from the chemistry of metal ion receptors[J]. Sciences, 2003,300(5621): 931-936.
75	WINKLER W C, BREAKER R R. Regulation of bacterial gene expression by riboswitches[J]. Ann. Rev. Microbiol., 2005,59: 487-517.
76	DANN C E I, WAKEMAN C A, SIELING C L, et al.. Structure and mechanism of a metal-sensing regulatory RNA[J]. Cell, 2007,130(5): 878-892.
77	WEINBERG Z, WANG J X, BOGUE J, et al.. Comparative genomics reveals 104 candidate structured RNAs from bacteria, archaea, and their metagenomes[J/OL]. Genome Biol., 2010,11(3):R31 [2021-08-28]. .
78	BAKER J L, SUDARSAN N, WEINBERG Z, et al.. Widespread genetic switches and toxicity resistance proteins for fluoride[J]. Sciences, 2012,335(6065): 233-235.
79	THAVARAJAH W, SILVERMAN A D, VEROSLOFF M S, et al.. Point-of-use detection of environmental fluoride via a cell-free riboswitch-based biosensor[J]. ACS Synth. Biol., 2020,9(1): 10-18.

传感器类别	优点	缺点
核糖开关传感器	应用范围广，识别元件可快速响应，高特异性和灵敏度，成本低	结构刚性不足，人工合成筛选
酶生物传感器	制备简便，高特异性	应用范围相对较窄，成本高，易失活，稳定性较低
免疫传感器	抗原抗体识别特异性好	应用范围相对较窄，成本高，稳定性较低
微生物传感器	成本低，耐久性好	稳定性、灵敏度低，响应时间久
细胞传感器	成本低，制作简便	应用范围有限，稳定性较低

传感器类别	优点	缺点
核糖开关传感器	应用范围广，识别元件可快速响应，高特异性和灵敏度，成本低	结构刚性不足，人工合成筛选
酶生物传感器	制备简便，高特异性	应用范围相对较窄，成本高，易失活，稳定性较低
免疫传感器	抗原抗体识别特异性好	应用范围相对较窄，成本高，稳定性较低
微生物传感器	成本低，耐久性好	稳定性、灵敏度低，响应时间久
细胞传感器	成本低，制作简便	应用范围有限，稳定性较低

[1]	雷豆豆, 马润然, 王伽伯, 孔维军. 食品中农药残留的新型生物检测技术研究进展[J]. 生物技术进展, 2023, 13(1): 1-10.
[2]	赵文卓, 李成勋, 胡作建, 余红秀. 功能核酸用于致病菌检测的研究进展[J]. 生物技术进展, 2023, 13(1): 30-38.
[3]	胡妍, 陈玲. 基于生物膜干涉技术检测PDL1抗体与PDL1抗原的亲和力[J]. 生物技术进展, 2021, 11(6): 795-801.
[4]	白小莲,爱军. 生物传感器在食源性致病菌大肠杆菌O157∶H7检测中的应用进展[J]. 生物技术进展, 2021, 11(3): 269-278.
[5]	陈硕,高佳奇,王迪,龙艳,李亮,张晓. DNA四面体纳米结构及其在生物技术领域的应用进展[J]. 生物技术进展, 2020, 10(6): 661-667.
[6]	杨苑,郭永福,唐浩智,张彪,史龚林,汪娅婷,杨俊,魏兰芳. 云南芒果采后炭疽病病原菌的鉴定及室内生防菌的筛选[J]. 生物技术进展, 2020, 10(4): 371-377.
[7]	张红兵,刘荟,史秀英,李会宣,范道春. 产油微藻的选育及其培养条件优化[J]. 生物技术进展, 2020, 10(3): 311-319.
[8]	杜再慧,罗云波,朱龙佼,许文涛,. DNA特殊二级结构及其应用进展[J]. 生物技术进展, 2019, 9(6): 563-570.
[9]	李凯,,罗云波,,许文涛,. CRISPR-Cas生物传感器研究进展[J]. 生物技术进展, 2019, 9(6): 579-591.
[10]	张玉昆,,安娜,刘卫晓,宛煜嵩,金芜军,李亮,张晓. 基于表面等离子体共振和电化学联用的DNA传感器研究进展[J]. 生物技术进展, 2019, 9(6): 592-598.
[11]	林晟豪,杜再慧,张秀杰,黄昆仑,,刘清亮4,许文涛,. 基于环介导等温扩增技术的生物传感器研究进展[J]. 生物技术进展, 2019, 9(6): 599-610.
[12]	杨文平,,吴远根. 基于Fe₃O₄过氧化物酶活性的Cd²⁺和Pb²⁺比色传感器[J]. 生物技术进展, 2019, 9(6): 611-619.
[13]	粟元,李舒婷,许文涛,. 气体生物传感器的识别机制研究进展[J]. 生物技术进展, 2019, 9(6): 620-626.
[14]	粟元,李舒婷,许文涛,. 气体生物传感器的应用研究进展[J]. 生物技术进展, 2019, 9(6): 627-632.
[15]	王心一,刘榜,谌阳,许文涛,周翔. 基于G-四联体比色生物传感器检测肉制品中羊源性成分[J]. 生物技术进展, 2019, 9(6): 641-646.

小分子靶标的核糖开关生物传感器研究进展

Research Progress of Riboswitch Biosensors for Small Molecule Target

RichHTML

PDF

可视化

摘要/Abstract

引用本文

使用本文

图/表 2

参考文献 79

相关文章 15

编辑推荐

Metrics

本文评价