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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2021, Vol. 41 Issue (5): 51-64    DOI: 10.13523/j.cb.2101024
综述     
末端脱氧核苷酸转移酶在生物传感及核酸合成领域的应用*
唐梦童1,2,3,王兆官1,2,3,李娇娇1,2,3,齐浩1,2,3,**()
1 天津大学化工学院 天津 300072
2 系统生物工程教育部重点实验室 天津 300072
3 天津化学化工协同创新中心合成生物学平台 天津 300072
Application of Terminal Deoxynucleotidyl Transferase in Biosensors and Nucleic Acid Synthesis
TANG Meng-tong1,2,3,WANG Zhao-guan1,2,3,LI Jiao-jiao1,2,3,QI Hao1,2,3,**()
1 School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
2 Key Laboratory of Systems Bioengineering of Ministry of Education, Syn Bio Research Platform, Tianjin University, Tianjin 300072, China
3 Collaborative Innovation Center of Chemical Science and Engineering, Tianjin University,Tianjin 300072,China
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摘要：

末端脱氧核苷酸转移酶(terminal deoxynucleotidyl transferase, TdT)是聚合酶X家族中的一员,与典型的DNA聚合酶不同,TdT以恒温的无模板依赖的方式催化脱氧核糖核苷三磷酸(dNTP)聚合到寡核苷酸的3'羟基端来合成DNA。并且TdT对底物的耐受性高具有聚合修饰型dNTP的能力,如荧光修饰的dNTP、生物素修饰的dNTP,甚至人工碱基均可作为其良好底物。TdT的这些生化特性使其被广泛的应用在生物传感和核酸合成领域中,促进了许多基于核酸的工具和方法的发展,并为酶促从头合成DNA技术的发展奠定基础。介绍了TdT的性质,重点总结了它在其介导的生物检测技术、核酸的修饰技术以及酶促合成DNA技术三个方面的核心作用、目前面临的挑战以及未来研究的方向,以期促进TdT在生物传感器和核酸合成中的进一步应用。
关键词： 末端脱氧核苷酸转移酶;  生物传感器;  修饰型核苷酸;  核酸合成    
Abstract:

Terminal deoxynucleotidyl transferase (TdT) is a member of the polymerase X family. Unlike typical DNA polymerases, TdT incorporates nucleotides at the 3'-end of single stranded DNA oligo in a unique template-free manner. Moreover, the high tolerance of TdT to substrates allows it to polymerize modified dNTP. Fluorescence-modified dNTPs, biotin-modified dNTPs and even artificial bases can be used as good substrates. These biochemical properties of TdT make it widely used in the fields of biosensing and nucleic acid synthesis, promote the development of many nucleic acid-based tools and methods, and lay the foundation for the development of enzymatic de novo DNA synthesis technology. The latest progress of cartilage 3D bioprinting and the limitations of current technology are also explained.
Key words: Terminal deoxynucleotide transferase    Biosensor    Modified nucleotides    Nucleic acid synthesis
收稿日期: 2021-01-19 出版日期: 2021-06-01
ZTFLH:  Q812  
基金资助: * 国家重点研发计划重点专项(2020YFA0712104)
通讯作者: 齐浩     E-mail: haoq@tju.edu.cn
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引用本文:

唐梦童,王兆官,李娇娇,齐浩. 末端脱氧核苷酸转移酶在生物传感及核酸合成领域的应用*[J]. 中国生物工程杂志, 2021, 41(5): 51-64.

TANG Meng-tong,WANG Zhao-guan,LI Jiao-jiao,QI Hao. Application of Terminal Deoxynucleotidyl Transferase in Biosensors and Nucleic Acid Synthesis. China Biotechnology, 2021, 41(5): 51-64.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2101024    或    https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I5/51

图1  X家族DNA聚合酶的结构域及TdT的三维结构
Target Linear range Limit of
detection		 Detection
time		 Signal
recognition		 Signal
transduction		 Output
signal		 Reference
TdT 0.4-90 U/mL 0.08 U/mL 60 min Nucleotide Electrochemistry Current [28]
Thrombin 0.5×105-1×105
pmol/L		 0.31 pmol/L 60 min Nucleotide
probe		 Electrochemistry Current [29]
Cardiac
troponin I		 0.5×102 -1×102
ng/mL		 40 pg/mL 80 min Aptamer Electrochemistry Current [30]
Mycotoxins 1×103-1×103
ng/mL		 0.85 ng/mL 80 min Nucleotide
probe		 Electrochemistry Current [31]
EcoRI
ExoIII		 0-10 U
0-4 U		 0.062 9 U/
0.008 67 U		 120 min Nucleotide Photochemistry Fluorescence [32]
Dam MTase 1.59×10-3
- 3.18×10-3 U/mL		 1.26×10-3
U/mL		 120 min Nucleotide Photochemistry Fluorescence [33]
Uracil-DNA
glycosylase		 2×10-5- 2×10-3
U/mL		 5×10-6 U/mL 210 min Nucleotide Photochemistry Fluorescence [34]
Exosome 3.6×102 - 7.19×106
particles/μL		 3.6×102
particles/μL		 90 min Aptamer Photochemistry Fluorescence [35]
miRNAs 5×10- 1×103
pmol/L		 200 pmol/L 480 min Nucleotide
probe		 Photochemistry Fluorescence [36]
Exosomes 9.75 × 103-1.95 × 106
particles/μL		 6.7 × 103
particles/μL		 90 min Antibody Photochemistry Visual light [37]
表1  部分基于TdT的生物传感器的汇总
图2  基于TdT的生物传感器的组成和原理
图3  TdT介导的DNA扩增信号转化为电信号的原理
图4  TdT介导的光学生物传感器的检测原理
图5  基于TdT扩增的外泌体检测系统的工作原理[50]
图6  修饰型核苷酸的化学结构以及TdT在核酸修饰中的应用
图7  单分子计数方法用于分析DNA损伤的原理示意图[65]
图8  两种酶促法合成DNA的策略
[1] Bell S P, Dutta A. DNA replication in eukaryotic cells. Annual Review of Biochemistry, 2002,71(1):333-374.
doi: 10.1146/annurev.biochem.71.110601.135425
[2] Lehman I R. Discovery of DNA polymerase. Journal of Biological Chemistry, 2003,278(37):34733-34738.
doi: 10.1074/jbc.X300002200
[3] Schmitt M W, Matsumoto Y, Loeb L A. High fidelity and lesion bypass capability of human DNA polymerase Δ. Biochimie, 2009,91(9):1163-1172.
doi: 10.1016/j.biochi.2009.06.007
[4] Beard W A, Wilson S H. Structure and mechanism of DNA polymerase Β. Chemical Reviews, 2006,106(2):361-382.
doi: 10.1021/cr0404904
[5] Suzuki T, Grúz P, Honma M, et al. Sensitivity of human cells expressing low-fidelity or weak-catalytic-activity variants of DNA polymerase ζ to genotoxic stresses. DNA Repair, 2016,45:34-43.
doi: 10.1016/j.dnarep.2016.06.002
[6] Motea E A, Berdis A J. Terminal deoxynucleotidyl transferase: The story of a misguided DNA polymerase. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2010,1804(5):1151-1166.
doi: 10.1016/j.bbapap.2009.06.030
[7] Tang L, Navarro L A, Chilkoti A, et al. High-molecular-weight polynucleotides by transferase-catalyzed living chain-growth polycondensation. Angewandte Chemie (International Ed in English), 2017,56(24):6778-6782.
doi: 10.1002/anie.201700991
[8] Bollum F J. Thermal conversion of nonpriming deoxyribonucleic acid to primer. The Journal of Biological Chemistry, 1959,234:2733-2734.
doi: 10.1016/S0021-9258(18)69770-4
[9] Boubakour-Azzouz I, Bertrand P, Claes A, et al. Terminal deoxynucleotidyl transferase requires KU80 and XRCC4 to promote N-addition at non-V(D)J chromosomal breaks in non-lymphoid cells. Nucleic Acids Research, 2012,40(17):8381-8391.
pmid: 22740656
[10] Purugganan M M, Shah S, Kearney J F, et al. Ku80 is required for addition of N nucleotides to V(D)J recombination junctions by terminal deoxynucleotidyl transferase. Nucleic Acids Research, 2001,29(7):1638-1646.
pmid: 11266568
[11] Thai T H, Purugganan M M, Roth D B, et al. Distinct and opposite diversifying activities of terminal transferase splice variants. Nature Immunology, 2002,3(5):457-462.
doi: 10.1038/ni788
[12] Thai T H, Kearney J F. Isoforms of terminal deoxynucleotidyltransferase: developmental aspects and function. Advances in Immunology. Amsterdam: Elsevier, 2005: 113-136.
[13] Bollum F J. Calf thymus polymerase. Journal of Biological Chemistry, 1960,235(8):2399-2403.
doi: 10.1016/S0021-9258(18)64634-4
[14] Deibel M R, Coleman M S. Biochemical properties of purified human terminal deoxynucleotidyltransferase. The Journal of Biological Chemistry, 1980,255(9):4206-4212.
doi: 10.1016/S0021-9258(19)85653-3
[15] Chang L M, Rafter E, Rusquet-Valerius R, et al. Expression and processing of recombinant human terminal transferase in the baculovirus system. The Journal of Biological Chemistry, 1988,263(25):12509-12513.
doi: 10.1016/S0021-9258(18)37784-6
[16] Boulé J B, Johnson E, Rougeon F, et al. High-level expression of murine terminal deoxynucleotidyl transferase in Escherichia coli grown at low temperature and overexpressingargU tRNA. Molecular Biotechnology, 1998,10(3):199-208.
doi: 10.1007/BF02740839
[17] Chua J P S, Go M K, Osothprarop T, et al. Evolving a thermostable terminal deoxynucleotidyl transferase. ACS Synthetic Biology, 2020,9(7):1725-1735.
doi: 10.1021/acssynbio.0c00078
[18] Delarue M, Boulé J B, Lescar J, et al. Crystal structures of a template-independent DNA polymerase: murine terminal deoxynucleotidyltransferase. The EMBO Journal, 2002,21(3):427-439.
doi: 10.1093/emboj/21.3.427
[19] Romain F, Barbosa I, Gouge J, et al. Conferring a template-dependent polymerase activity to terminal deoxynucleotidyltransferase by mutations in the Loop1 region. Nucleic Acids Research, 2009,37(14):4642-4656.
doi: 10.1093/nar/gkp460 pmid: 19502493
[20] Gangi-Peterson L, Sorscher D H, Reynolds J W, et al. Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination. Journal of Clinical Investigation, 1999,103(6):833-841.
pmid: 10079104
[21] Loc’H J, Rosario S, Delarue M. Structural basis for a new templated activity by terminal deoxynucleotidyl transferase: implications for V(D)J recombination. Structure, 2016,24(9):1452-1463.
doi: 10.1016/j.str.2016.06.014
[22] Anderson R S, Bollum F J, Beattie K L. Pyrophosphorolytic dismutation of oligodeoxy-nucleotides by terminal deoxynucleotidyltransferase. Nucleic Acids Research, 1999,27(15):3190-3196.
pmid: 10454617
[23] Boulé J B, Rougeon F, Papanicolaou C. Terminal deoxynucleotidyl transferase indiscriminately incorporates ribonucleotides and deoxyribonucleotides. Journal of Biological Chemistry, 2001,276(33):31388-31393.
doi: 10.1074/jbc.M105272200
[24] Goering A W, Li J, McClure R A, et al. In vitro reconstruction of nonribosomal peptide biosynthesis directly from DNA using cell-free protein synthesis. ACS Synthetic Biology, 2017,6(1):39-44.
doi: 10.1021/acssynbio.6b00160
[25] Röthlisberger P, Levi-Acobas F, Leumann C J, et al. Enzymatic synthesis of biphenyl-DNA oligonucleotides. Bioorganic & Medicinal Chemistry, 2020,28(11):115487.
doi: 10.1016/j.bmc.2020.115487
[26] Berdis A J, McCutcheon D. The use of non-natural nucleotides to probe template-independent DNA synthesis. ChemBioChem, 2007,8(12):1399-1408.
doi: 10.1002/(ISSN)1439-7633
[27] Gouge J, Rosario S, Romain F, et al. Structures of intermediates along the catalytic cycle of terminal deoxynucleotidyltransferase: dynamical aspects of the two-metal ion mechanism. Journal of Molecular Biology, 2013,425(22):4334-4352.
doi: 10.1016/j.jmb.2013.07.009
[28] Chang L M, Bollum F J. Multiple roles of divalent cation in the terminal deoxynucleotidyltransferase reaction. Journal of Biological Chemistry, 1990,265(29):17436-17440.
doi: 10.1016/S0021-9258(18)38181-X
[29] Yuan Y J, Li W H, Liu Z L, et al. A versatile biosensing system for DNA-related enzyme activity assay via the synthesis of silver nanoclusters using enzymatically-generated DNA as template. Biosensors and Bioelectronics, 2014,61:321-327.
doi: 10.1016/j.bios.2014.05.038
[30] Lei S, Liu Z, Xu L L, et al. A “signal-on” electrochemical biosensor based on DNAzyme-driven bipedal DNA walkers and TdT-mediated cascade signal amplification strategy. Analytica Chimica Acta, 2020,1100:40-46.
doi: 10.1016/j.aca.2019.12.008
[31] Yuan P X, Deng S Y, Zheng C Y, et al. In situ formed copper nanoparticles templated by TdT-mediated DNA for enhanced SPR sensor-based DNA assay. Biosensors and Bioelectronics, 2017,97:1-7.
doi: 10.1016/j.bios.2017.05.033
[32] 张媛, 梁嘉慧, 罗云波, 等. 末端脱氧核酸转移酶介导的功能核酸生物传感器研究进展. 生物技术通报, 2019,35(1):161-169.
Zhang Y, Liang J H, Luo Y B, et al. Research progress on functional nucleic acid biosensors mediated by terminal deoxynucleotidyl transferase. Biotechnology Bulletin, 2019,35(1):161-169.
[33] Abnous K, Danesh N M, Nameghi M A, et al. An ultrasensitive electrochemical sensing method for detection of microcystin-LR based on infinity-shaped DNA structure using double aptamer and terminal deoxynucleotidyl transferase. Biosensors and Bioelectronics, 2019,144:111674.
doi: 10.1016/j.bios.2019.111674
[34] Zhao Y J, Ma W J, Zou S Z, et al. Terminal deoxynucleotidyl transferase-initiated molecule beacons arrayed aptamer probe for sensitive detection of metastatic colorectal cancer cells. Talanta, 2019,202:152-158.
doi: 10.1016/j.talanta.2019.04.065
[35] Fan K M, Zheng C K, Zhao Y Y, et al. Label-free ultrasensitive determination of EcoRI activity based on terminal deoxynucleotidyl transferase generated G-quadruplexes. Microchemical Journal, 2018,143:286-291.
doi: 10.1016/j.microc.2018.08.024
[36] Wang L, Pan Y H, Liu Y F, et al. Fabrication of an aptamer-coated liposome complex for the detection and profiling of exosomes based on terminal deoxynucleotidyl transferase-mediated signal amplification. ACS Applied Materials & Interfaces, 2020,12(1):322-329.
[37] Du Y M, Zhou Y Y, Wen Y L, et al. Multiplexed aptasensing of food contaminants by using terminal deoxynucleotidyl transferase-produced primer-triggered rolling circle amplification: application to the colorimetric determination of enrofloxacin, lead (II), Escherichia coli O157: H7 and tropomyosin. Microchimica Acta, 2019,186(12):1-10.
doi: 10.1007/s00604-018-3127-5
[38] Hu Y F, Zhang Q Q, Guo Z Y, et al. In situ grown DNA nanotail-templated silver nanoclusters enabling label-free electrochemical sensing of terminal deoxynucleotidyl transferase activity. Biosensors and Bioelectronics, 2017,98:91-99.
doi: 10.1016/j.bios.2017.06.017
[39] Huang X Y, Niu W C, Wu J Y, et al. A triple-amplification differential pulse voltammetry for sensitive detection of DNA based on exonuclease III, strand displacement reaction and terminal deoxynucleotidyl transferase. Biosensors and Bioelectronics, 2019,143:111609.
doi: 10.1016/j.bios.2019.111609
[40] Lang M J, Luo D, Yang G Y, et al. An ultrasensitive electrochemical sensing platform for the detection of cTnI based on aptamer recognition and signal amplification assisted by TdT. RSC Advances, 2020,10(60):36396-36403.
doi: 10.1039/D0RA05171C
[41] Wang Y, Zhang X D, Zhan Y X, et al. Au@Fe3O4 nanocomposites as conductive bridges coupled with a bi-enzyme-aided system to mediate gap-electrical signal transduction for homogeneous aptasensor mycotoxins detection. Sensors and Actuators B: Chemical, 2020,321:128553.
doi: 10.1016/j.snb.2020.128553
[42] Chen X L, Cao G H, Wang X F, et al. Terminal deoxynucleotidyl transferase induced activators to unlock the trans-cleavage of CRISPR/Cpf 1 (TdT-IU- CRISPR/Cpf 1): an ultrasensitive biosensor for Dam MTase activity detection. Biosensors and Bioelectronics, 2020,163:112271.
doi: 10.1016/j.bios.2020.112271
[43] Du Y C, Wang S Y, Wang Y X, et al. Terminal deoxynucleotidyl transferase combined CRISPR-Cas12a amplification strategy for ultrasensitive detection of uracil-DNA glycosylase with zero background. Biosensors and Bioelectronics, 2021,171:112734.
doi: 10.1016/j.bios.2020.112734
[44] He J L, Mei T T, Tang L, et al. DSN/TdT recycling digestion based cyclic amplification strategy for microRNA assay. Talanta, 2020,219:121173.
doi: 10.1016/j.talanta.2020.121173
[45] Chen M J, Ma C B, Yan Y, et al. A label-free fluorescence method based on terminal deoxynucleotidyl transferase and thioflavin T for detecting prostate-specific antigen. Analytical and Bioanalytical Chemistry, 2019,411(22):5779-5784.
doi: 10.1007/s00216-019-01958-0
[46] Que H Y, Yan X Y, Guo B, et al. Terminal deoxynucleotidyl transferase and rolling circle amplification induced G-triplex formation: a label-free fluorescent strategy for DNA methyltransferase activity assay. Sensors and Actuators B: Chemical, 2019,291:394-400.
doi: 10.1016/j.snb.2019.04.091
[47] Liu G R, He W L, Liu C H. Sensitive detection of uracil-DNA glycosylase (UDG) activity based on terminal deoxynucleotidyl transferase-assisted formation of fluorescent copper nanoclusters (CuNCs). Talanta, 2019,195:320-326.
doi: 10.1016/j.talanta.2018.11.083
[48] Li Y T, Tang D H, Zhu L, et al. Label-free detection of miRNA cancer markers based on terminal deoxynucleotidyl transferase-induced copper nanoclusters. Analytical Biochemistry, 2019,585:113346.
doi: 10.1016/j.ab.2019.113346
[49] Wang Y, Liu J, Zhou H. Visual detection of Cucumber green mottle mosaic virus based on terminal deoxynucleotidyl transferase coupled with DNAzymes amplification. Sensors (Basel, Switzerland), 2019,19(6):E1298.
[50] Huang Z P, Lin Q Y, Ye X, et al. Terminal deoxynucleotidyl transferase based signal amplification for enzyme-linked aptamer-sorbent assay of colorectal cancer exosomes. Talanta, 2020,218:121089.
doi: 10.1016/j.talanta.2020.121089
[51] Zamecnik P C, Stephenson M L. Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide. Proceedings of the National Academy of Sciences of the United States of America, 1978,75(1):280-284.
[52] Dey S, Sczepanski J T. In vitro selection of l-DNA aptamers that bind a structured d-RNA molecule. Nucleic Acids Research, 2020,48(4):1669-1680.
doi: 10.1093/nar/gkz1236
[53] Meltzer J C, Sanders V, Grimm P C, et al. Nonradioactive Northern blotting with biotinylated and digoxigenin-labeled RNA probes. Electrophoresis, 1998,19(8-9):1351-1355.
pmid: 9694280
[54] Wang Y Q, Cheng J, Zhao D, et al. Designed DNA nanostructure grafted with erlotinib for non-small-cell lung cancer therapy. Nanoscale, 2020,12(47):23953-23958.
doi: 10.1039/D0NR06945K
[55] Zhang L, Yang Y B, Tan J, et al. Chemically modified nucleic acid biopolymers used in biosensing. Materials Chemistry Frontiers, 2020,4(5):1315-1327.
doi: 10.1039/D0QM00026D
[56] Caruthers M H. A brief review of DNA and RNA chemical synthesis. Biochemical Society Transactions, 2011,39(2):575-580.
doi: 10.1042/BST0390575 pmid: 21428942
[57] Jakubovska J, Tauraitè D, Birštonas L, et al. N4-acyl-2'-deoxycytidine-5'-triphosphates for the enzymatic synthesis of modified DNA . Nucleic Acids Research, 2018,46(12):5911-5923.
doi: 10.1093/nar/gky435 pmid: 29846697
[58] Obeid S, Baccaro A, Welte W, et al. Structural basis for the synthesis of nucleobase modified DNA by Thermus aquaticus DNA polymerase. Proceedings of the National Academy of Sciences of the United States of America, 2010,107(50):21327-21331.
[59] Evans S J, Fogg M J, Mamone A, et al. Improving dideoxynucleotide-triphosphate utilisation by the hyper-thermophilic DNA polymerase from the archaeon Pyrococcus furiosus. Nucleic Acids Research, 2000,28(5):1059-1066.
pmid: 10666444
[60] Guerra C E. Analysis of oligonucleotide microarrays by 3' end labeling using fluorescent nucleotides and terminal transferase. BioTechniques, 2006,41(1):53-56.
pmid: 16869513
[61] Jahn K, Tørring T, Voigt N V, et al. Functional patterning of DNA origami by parallel enzymatic modification. Bioconjugate Chemistry, 2011,22(4):819-823.
doi: 10.1021/bc2000098
[62] Lukoseviciute M, Ling I T C, Senanayake U, et al. Tissue-specific in vivo biotin chromatin immunoprecipitation with sequencing in zebrafish and chicken. STAR Protocols, 2020,1(2):100066.
doi: 10.1016/j.xpro.2020.100066
[63] Lin K, Yan Q, Mitchell A, et al. A simple method for non-denaturing purification of biotin-tagged proteins through competitive elution with free biotin. BioTechniques, 2020,68(1):41-44.
doi: 10.2144/btn-2019-0088
[64] Jang E K, Son R G, Pack S P. Novel enzymatic single-nucleotide modification of DNA oligomer: prevention of incessant incorporation of nucleotidyl transferase by ribonucleotide-borate complex. Nucleic Acids Research, 2019,47(17):e102.
doi: 10.1093/nar/gkz612
[65] Zhang Y, Hua R N, Zhang C Y. Analysis of the isolated and the clustered DNA damages by single-molecule counting. Analytical Chemistry, 2019,91(16):10381-10385.
doi: 10.1021/acs.analchem.9b02694 pmid: 31364352
[66] Miura F, Fujino T, Kogashi K, et al. Triazole linking for preparation of a next-generation sequencing library from single-stranded DNA. Nucleic Acids Research, 2018,46(16):e95.
doi: 10.1093/nar/gky452
[67] Feldman A, Dien V T, Karadeema R J, et al. Optimization of replication, transcription, and translation in a semi-synthetic organism. Journal of the American Chemical Society, 2019,141(27):10644-10653.
doi: 10.1021/jacs.9b02075 pmid: 31241334
[68] Zhang Y, Ptacin J L, Fischer E C, et al. A semi-synthetic organism that stores and retrieves increased genetic information. Nature, 2017,551(7682):644-647.
doi: 10.1038/nature24659
[69] Galindo-Murillo R, Barroso-Flores J. Hydrophobic unnatural base pairs show a Watson-Crick pairing in micro-second molecular dynamics simulations. Journal of Biomolecular Structure and Dynamics, 2020,38(14):4098-4106.
doi: 10.1080/07391102.2019.1671898
[70] Lavergne T, Malyshev D A, Romesberg F E. Major groove substituents and polymerase recognition of a class of predominantly hydrophobic unnatural base pairs. Chemistry (Weinheim an Der Bergstrasse, Germany), 2012,18(4):1231-1239.
[71] Singh I, Laos R, Hoshika S, et al. Snapshots of an evolved DNA polymerase pre- and post-incorporation of an unnatural nucleotide. Nucleic Acids Research, 2018,46(15):7977-7988.
doi: 10.1093/nar/gky552 pmid: 29986111
[72] Hoshika S, Leal N A, Kim M J, et al. Hachimoji DNA and RNA: a genetic system with eight building blocks. Science (New York), 2019,363(6429):884-887.
doi: 10.1126/science.aat0971
[73] Kobayashi T, Takezawa Y, Sakamoto A, et al. Enzymatic synthesis of ligand-bearing DNAs for metal-mediated base pairing utilising a template-independent polymerase. Chemical Communications (Cambridge, England), 2016,52(19):3762-3765.
doi: 10.1039/C5CC10039A
[74] Röthlisberger P, Levi-Acobas F, Sarac I, et al. On the enzymatic incorporation of an imidazole nucleotide into DNA. Organic & Biomolecular Chemistry, 2017,15(20):4449-4455.
[75] Röthlisberger P, Levi-Acobas F, Sarac I, et al. Towards the enzymatic formation of artificial metal base pairs with a carboxy-imidazole-modified nucleotide. Journal of Inorganic Biochemistry, 2019,191:154-163.
doi: S0162-0134(18)30503-8 pmid: 30529723
[76] Templin M F, Stoll D, Schrenk M, et al. Protein microarray technology. Trends in Biotechnology, 2002,20(4):160-166.
doi: 10.1016/S0167-7799(01)01910-2
[77] Tsai H, Doong R, Lin C. A strategy for multi-protein-immobilization using N-succinimidyl 4-benzoylbenzoic acid as the photolabile ligand. Japan Society for Analytical Chemistry, 2002,17:269-272.
[78] Takahara M, Hayashi K, Goto M, et al. Enzymatic conjugation of multiple proteins on a DNA aptamer in a tail-specific manner. Biotechnology Journal, 2016,11(6):814-823.
doi: 10.1002/biot.201500560 pmid: 27119459
[79] Takahara M, Wakabayashi R, Minamihata K, et al. Primary amine-clustered DNA aptamer for DNA-protein conjugation catalyzed by microbial transglutaminase. Bioconjugate Chemistry, 2017,28(12):2954-2961.
doi: 10.1021/acs.bioconjchem.7b00594 pmid: 29131594
[80] Jang E K, Ki M R, Pack S P. Design of reactive-end DNA oligomers via incorporation of oxanine into oligonucleotides using terminal deoxynucleotidyl transferase. Process Biochemistry, 2017,62:99-105.
doi: 10.1016/j.procbio.2017.07.011
[81] Jensen M A, Davis R W. Template-independent enzymatic oligonucleotide synthesis (TiEOS): its history, prospects, and challenges. Biochemistry, 2018,57(12):1821-1832.
doi: 10.1021/acs.biochem.7b00937
[82] Palluk S, Arlow D H, de Rond de Rond, et al. De novo DNA synthesis using polymerase-nucleotide conjugates. Nature Biotechnology, 2018,36(7):645-650.
doi: 10.1038/nbt.4173
[83] Jensen M A, Griffin P, Davis R W. Free-running enzymatic oligonucleotide synthesis for data storage applications. bioRxiv, 2018: 355719.
[84] Lee H H, Kalhor R, Goela N, et al. Terminator-free template-independent enzymatic DNA synthesis for digital information storage. Nature Communications, 2019,10:2383.
doi: 10.1038/s41467-019-10258-1
[85] Lee H, Wiegand D J, Griswold K, et al. Photon-directed multiplexed enzymatic DNA synthesis for molecular digital data storage. Nature Communications, 2020,11:5246.
doi: 10.1038/s41467-020-18681-5
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