Artificial enzyme

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For enzyme mimic, see enzyme mimic.
See also: Artificial metalloenzyme
Schematic drawing of artificial phosphorylase

An artificial enzyme is a synthetic organic molecule or ion that recreates one or more functions of a natural enzyme. These molecules aim to achieve catalysis with rates and selectivity comparable to those of naturally occurring enzymes.[1][2]

History

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Natural enzymes catalyze chemical reactions with high selectivity and efficiency. Catalysis occurs in the enzyme's active site, where substrates bind near functional groups, enabling proximity effects. Artificial enzymes mimic this by combining substrate-binding sites (e.g., cyclodextrins, crown ethers, or calixarenes) with catalytic groups in small molecules.[1][2]

Advances include artificial enzymes based on amino acids or peptides, such as scaffolded histidine residues mimicking metalloproteins like hemocyanin, tyrosinase, and catechol oxidase.[3] Computational design using tools like Rosetta has enabled de novo creation of artificial enzymes.[4] In 2014, enzymes were created from non-natural molecules.[5] A 2016 book chapter discussed future directions in artificial enzymes.[6]

Nanozymes

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Nanozymes are nanomaterials exhibiting enzyme-like properties,[7][8] first coined in 2004.[9] They have applications in biosensing, bioimaging, tumor therapy, and anti-biofouling.[10][11] Unlike natural enzymes, nanozymes offer stability, multifunctionality, and scalability.[12]

Development and Key Milestones

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Early discoveries in the 1990s included fullerene derivatives mimicking superoxide dismutase (SOD).[13] The 2000s saw the term "nanozyme" formalized and applications expand, such as nanoceria preventing retinal degeneration[14] and peroxidase-like activity in ferromagnetic nanoparticles for immunoassays.[15]

The 2010s brought numerous reviews and applications, including colorimetric assays,[16] tumor visualization,[17] and anti-biofouling.[18] Key books and reviews emerged, summarizing progress.[19][10]

In the 2020s, nanozymes advanced in therapeutic applications, such as single-atom nanozymes for sepsis[20] and tumor therapy.[21] Strategies like data-informed discovery[22] and machine learning aided discovery,[23] and applications in treating conditions like Parkinson's disease and inflammatory bowel disease were reported.[24][25] Nanozymes were recognized as one of IUPAC's Top Ten Emerging Technologies in Chemistry in 2022.[26] Nanozyme is among the Top 10 Emerging Technologies of 2025 Summer Davos.[27] A monograph entitled nanozymes was published in Chinese (《纳米酶》).[28]

See also

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References

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  1. ^ a b Breslow, Ronald (2006). Artificial Enzymes. John Wiley & Sons. ISBN 978-3-527-60680-1.
  2. ^ a b Kirby, Anthony John; Hollfelder, Florian (2009). From Enzyme Models to Model Enzymes. Royal Society of Chemistry. ISBN 978-0-85404-175-6.
  3. ^ Albada, H. Bauke; Soulimani, Fouad; Weckhuysen, Bert M.; Liskamp, Rob M. J. (2007). "Scaffolded amino acids as a close structural mimic of type-3 copper binding sites". Chemical Communications (46): 4895–7. doi:10.1039/b709400k. PMID 18361361.
  4. ^ Röthlisberger, Daniela; Khersonsky, Olga; Wollacott, Andrew M.; Jiang, Lin; DeChancie, Jason; Betker, Jamie; Gallaher, Jasmine L.; Althoff, Eric A.; Zanghellini, Alexandre; Dym, Orly; Albeck, Shira; Houk, Kendall N.; Tawfik, Dan S.; Baker, David (19 March 2008). "Kemp elimination catalysts by computational enzyme design". Nature. 453 (7192): 190–195. Bibcode:2008Natur.453..190R. doi:10.1038/nature06879. PMID 18354394.
  5. ^ "World's first artificial enzymes created using synthetic biology". University of Cambridge. 1 December 2014. Retrieved 14 December 2016.
  6. ^ Cheng, Hanjun; Wang, Xiaoyu; Wei, Hui (2016). "Artificial Enzymes: The Next Wave". In Wang, Zerong (ed.). Encyclopedia of Physical Organic Chemistry. American Cancer Society. doi:10.1002/9781118468586. ISBN 978-1-118-47045-9.
  7. ^ Wei, Hui; Wang, Erkang (2013). "Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes". Chemical Society Reviews. 42 (14): 6060–93. doi:10.1039/c3cs35486e. PMID 23740388. S2CID 39693417.
  8. ^ https://pubs.rsc.org/en/content/articlepdf/2019/cs/c8cs00457a
  9. ^ Manea, Flavio; Houillon, Florence Bodar; Pasquato, Lucia; Scrimin, Paolo (19 November 2004). "Nanozymes: Gold-Nanoparticle-Based Transphosphorylation Catalysts". Angewandte Chemie International Edition. 43 (45): 6165–6169. doi:10.1002/anie.200460649. PMID 15549744.
  10. ^ a b Wu, Jiangjiexing; Wang, Xiaoyu; Wang, Quan; Lou, Zhangping; Li, Sirong; Zhu, Yunyao; Qin, Li; Wei, Hui (2019). "Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II)". Chemical Society Reviews. 48 (4): 1004–1076. doi:10.1039/c8cs00457a. PMID 30534770. S2CID 54474779.
  11. ^ Wang, Xiaoyu; Hu, Yihui; Wei, Hui (2016). "Nanozymes in bionanotechnology: from sensing to therapeutics and beyond". Inorganic Chemistry Frontiers. 3 (1): 41–60. doi:10.1039/c5qi00240k. S2CID 138012998.
  12. ^ Wei, Hui; Wang, Erkang (2013). "Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes". Chemical Society Reviews. 42 (14): 6060–93. doi:10.1039/c3cs35486e. PMID 23740388. S2CID 39693417.
  13. ^ Dugan, Laura L.; Gabrielsen, Joseph K.; Yu, Shan P.; Lin, Tien-Sung; Choi, Dennis W. (April 1996). "Buckminsterfullerenol Free Radical Scavengers Reduce Excitotoxic and Apoptotic Death of Cultured Cortical Neurons". Neurobiology of Disease. 3 (2): 129–135. doi:10.1006/nbdi.1996.0013. PMID 9173920. S2CID 26139075.
  14. ^ Chen, Junping; Patil, Swanand; Seal, Sudipta; McGinnis, James F. (29 October 2006). "Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides". Nature Nanotechnology. 1 (2): 142–150. Bibcode:2006NatNa...1..142C. doi:10.1038/nnano.2006.91. PMID 18654167. S2CID 3093558.
  15. ^ Gao, Lizeng; Zhuang, Jie; Nie, Leng; Zhang, Jinbin; Zhang, Yu; Gu, Ning; Wang, Taihong; Feng, Jing; Yang, Dongling; Perrett, Sarah; Yan, Xiyun (26 August 2007). "Intrinsic peroxidase-like activity of ferromagnetic nanoparticles". Nature Nanotechnology. 2 (9): 577–583. Bibcode:2007NatNa...2..577G. doi:10.1038/nnano.2007.260. PMID 18654371. S2CID 10602418.
  16. ^ Wei, Hui; Wang, Erkang (March 2008). "Fe3O4 Magnetic Nanoparticles as Peroxidase Mimetics and Their Applications in H2O2 and Glucose Detection". Analytical Chemistry. 80 (6): 2250–2254. doi:10.1021/ac702203f. PMID 18290671.
  17. ^ Fan, Kelong; Cao, Changqian; Pan, Yongxin; Lu, Di; Yang, Dongling; Feng, Jing; Song, Lina; Liang, Minmin; Yan, Xiyun (17 June 2012). "Magnetoferritin nanoparticles for targeting and visualizing tumour tissues". Nature Nanotechnology. 7 (7): 459–464. Bibcode:2012NatNa...7..459F. doi:10.1038/nnano.2012.90. PMID 22706697. S2CID 19859273.
  18. ^ Natalio, Filipe; André, Rute; Hartog, Aloysius F.; Stoll, Brigitte; Jochum, Klaus Peter; Wever, Ron; Tremel, Wolfgang (1 July 2012). "Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart biofilm formation". Nature Nanotechnology. 7 (8): 530–535. Bibcode:2012NatNa...7..530N. doi:10.1038/nnano.2012.91. PMID 22751222.
  19. ^ Wang, Xiaoyu; Guo, Wenjing; Hu, Yihui; Wu, Jiangjiexing; Wei, Hui (2016). Nanozymes: Next Wave of Artificial Enzymes. Springer. ISBN 978-3-662-53068-9.
  20. ^ Cao, Fangfang; Zhang, Lu; You, Yawen; Zheng, Lirong; Ren, Jinsong; Qu, Xiaogang (12 February 2020). "An Enzyme-Mimicking Single-Atom Catalyst as an Efficient Multiple Reactive Oxygen and Nitrogen Species Scavenger for Sepsis Management". Angewandte Chemie. 132 (13): 5146–5153. Bibcode:2020AngCh.132.5146C. doi:10.1002/ange.201912182. S2CID 214232731.
  21. ^ Wang, Dongdong; Wu, Huihui; Phua, Soo Zeng Fiona; Yang, Guangbao; Qi Lim, Wei; Gu, Long; Qian, Cheng; Wang, Haibao; Guo, Zhen; Chen, Hongzhong; Zhao, Yanli (17 January 2020). "Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor". Nature Communications. 11 (1): 357. Bibcode:2020NatCo..11..357W. doi:10.1038/s41467-019-14199-7. PMC 6969186. PMID 31953423.
  22. ^ https://www.nature.com/articles/s41467-022-28344-2
  23. ^ Wei, Yonghua; Wu, Jin; Wu, Yixuan; Liu, Hongjiang; Meng, Fanqiang; Liu, Qiqi; Midgley, Adam C.; Zhang, Xiangyun; Qi, Tianyi; Kang, Helong; Chen, Rui; Kong, Deling; Zhuang, Jie; Yan, Xiyun; Huang, Xinglu (2022). "Prediction and Design of Nanozymes using Explainable Machine Learning". Advanced Materials. 34 (27) e2201736. Bibcode:2022AdM....3401736W. doi:10.1002/adma.202201736. PMID 35487518. S2CID 248451764.
  24. ^ Singh, Namrata; Savanur, Mohammed Azharuddin; Srivastava, Shubhi; D'Silva, Patrick; Mugesh, Govindasamy (6 November 2017). "A Redox Modulatory Mn3O4 Nanozyme with Multi-Enzyme Activity Provides Efficient Cytoprotection to Human Cells in a Parkinson's Disease Model". Angewandte Chemie International Edition. 56 (45): 14267–14271. doi:10.1002/anie.201708573. PMID 28922532.
  25. ^ Zhao, Shuai; Duan, Hongxia; Yang, Yili; Yan, Xiyun; Fan, Kelong (November 2019). "Fenozyme Protects the Integrity of the Blood–Brain Barrier against Experimental Cerebral Malaria". Nano Letters. 19 (12): 8887–8895. Bibcode:2019NanoL..19.8887Z. doi:10.1021/acs.nanolett.9b03774. PMID 31671939. S2CID 207815491.
  26. ^ Meyers, Fabienne (October 17, 2022). "IUPAC Announces the 2022 Top Ten Emerging Technologies in Chemistry". IUPAC | International Union of Pure and Applied Chemistry.
  27. ^ https://www.weforum.org/stories/2025/06/top-10-emerging-technologies-of-2025/
  28. ^ https://mp.weixin.qq.com/s/ZcjrFghDz2umTx0wX0vErg