Artificial enzyme

{{Short description|Synthetic organic molecule or ion that recreates one or more functions of an enzyme}} {{For|enzyme mimic|enzyme mimic}} {{See also|Artificial metalloenzyme}} thumb|310px|Schematic drawing of artificial phosphorylase

An '''artificial enzyme''', also known as a '''synthetic enzyme''' or a '''synzyme''', 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.<ref name="Breslow2006">{{cite book |last1=Breslow |first1=Ronald |title=Artificial Enzymes |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60680-1 }}</ref><ref name="Kirby2009">{{cite book |last1=Kirby |first1=Anthony John |last2=Hollfelder |first2=Florian |title=From Enzyme Models to Model Enzymes |date=2009 |publisher=Royal Society of Chemistry |isbn=978-0-85404-175-6 }}</ref>

Current synzymes consist mainly of organic molecules tailored in such a way that they catalyse certain kinds of reactions. Like enzymes, they bind a transition state of a substrate in an active site, and like enzymes they generally obey Michaelis–Menten kinetics.

== History == 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.<ref name="Breslow2006" /><ref name="Kirby2009" />

Advances include artificial enzymes based on amino acids or peptides, such as scaffolded histidine residues mimicking metalloproteins like hemocyanin, tyrosinase, and catechol oxidase.<ref>{{cite journal |last1=Albada |first1=H. Bauke |last2=Soulimani |first2=Fouad |last3=Weckhuysen |first3=Bert M. |last4=Liskamp |first4=Rob M. J. |title=Scaffolded amino acids as a close structural mimic of type-3 copper binding sites |journal=Chemical Communications |date=2007 |issue=46 |pages=4895–7 |doi=10.1039/b709400k |pmid=18361361 }}</ref> Computational design using tools like Rosetta has enabled de novo creation of artificial enzymes.<ref>{{cite journal |last1=Röthlisberger |first1=Daniela |last2=Khersonsky |first2=Olga |last3=Wollacott |first3=Andrew M. |last4=Jiang |first4=Lin |last5=DeChancie |first5=Jason |last6=Betker |first6=Jamie |last7=Gallaher |first7=Jasmine L. |last8=Althoff |first8=Eric A. |last9=Zanghellini |first9=Alexandre |last10=Dym |first10=Orly |last11=Albeck |first11=Shira |last12=Houk |first12=Kendall N. |last13=Tawfik |first13=Dan S. |last14=Baker |first14=David |title=Kemp elimination catalysts by computational enzyme design |journal=Nature |date=19 March 2008 |volume=453 |issue=7192 |pages=190–195 |doi=10.1038/nature06879 |pmid=18354394 |bibcode=2008Natur.453..190R |doi-access=free }}</ref> In 2014, enzymes were created from non-natural molecules.<ref name="allart">{{cite web |url=http://www.cam.ac.uk/research/news/worlds-first-artificial-enzymes-created-using-synthetic-biology |title=World's first artificial enzymes created using synthetic biology |date=1 December 2014 |publisher=University of Cambridge |access-date=14 December 2016}}</ref> A 2016 book chapter discussed future directions in artificial enzymes.<ref name="Cheng, Wang & Hui 2016">{{cite book |title=Encyclopedia of Physical Organic Chemistry |chapter=Artificial Enzymes: The Next Wave |year=2016 |publisher=American Cancer Society |isbn=978-1-118-47045-9 |editor1-last=Wang |editor1-first=Zerong |first1=Hanjun |last1=Cheng |first2=Xiaoyu |last2=Wang |first3=Hui |last3=Wei |doi=10.1002/9781118468586 }}</ref>

==Examples== If [Ru(NH₃)₅]³⁺ is attached to certain histidine residues in a myoglobin protein, myoglobin is no longer a passive oxygen carrier, but gains enzymatic activity of an oxidase. Ascorbic acid is oxidised with molecular oxygen.

Cyclodextrins are cap structures with a hydrophilic exterior but a hydrophobic interior. If pyridoxal is anchored in the interior the cyclodextran shows transaminase activity.

== Nanozymes == '''Nanozymes''' are nanomaterials exhibiting enzyme-like properties,<ref name="auto">{{cite journal |last1=Wei |first1=Hui |last2=Wang |first2=Erkang |s2cid=39693417 |title=Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes |journal=Chemical Society Reviews |date=2013 |volume=42 |issue=14 |pages=6060–93 |doi=10.1039/c3cs35486e |pmid=23740388 |bibcode=2013CSRev..42.6060W }}</ref><ref>{{Cite journal |last1=Wu |first1=Jiangjiexing |last2=Wang |first2=Xiaoyu |last3=Wang |first3=Quan |last4=Lou |first4=Zhangping |last5=Li |first5=Sirong |last6=Zhu |first6=Yunyao |last7=Qin |first7=Li |last8=Wei |first8=Hui |date=2019 |title=Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II) |url=https://xlink.rsc.org/?DOI=C8CS00457A |journal=Chemical Society Reviews |language=en |volume=48 |issue=4 |pages=1004–1076 |doi=10.1039/C8CS00457A |pmid=30534770 |bibcode=2019CSRev..48.1004W |issn=0306-0012|url-access=subscription }}</ref> first coined in 2004.<ref>{{cite journal |last1=Manea |first1=Flavio |last2=Houillon |first2=Florence Bodar |last3=Pasquato |first3=Lucia |last4=Scrimin |first4=Paolo |title=Nanozymes: Gold-Nanoparticle-Based Transphosphorylation Catalysts |journal=Angewandte Chemie International Edition |date=19 November 2004 |volume=43 |issue=45 |pages=6165–6169 |doi=10.1002/anie.200460649 |pmid=15549744 }}</ref> They have applications in biosensing, bioimaging, tumor therapy, and anti-biofouling.<ref name="pmid30534770">{{cite journal |last1=Wu |first1=Jiangjiexing |last2=Wang |first2=Xiaoyu |last3=Wang |first3=Quan |last4=Lou |first4=Zhangping |last5=Li |first5=Sirong |last6=Zhu |first6=Yunyao |last7=Qin |first7=Li |last8=Wei |first8=Hui |title=Nanomaterials with enzyme-like characteristics (nanozymes): next-generation artificial enzymes (II) |journal=Chemical Society Reviews |date=2019 |volume=48 |issue=4 |pages=1004–1076 |doi=10.1039/c8cs00457a |pmid=30534770 |bibcode=2019CSRev..48.1004W |s2cid=54474779 }}</ref><ref>{{cite journal |last1=Wang |first1=Xiaoyu |last2=Hu |first2=Yihui |last3=Wei |first3=Hui |s2cid=138012998 |title=Nanozymes in bionanotechnology: from sensing to therapeutics and beyond |journal=Inorganic Chemistry Frontiers |date=2016 |volume=3 |issue=1 |pages=41–60 |doi=10.1039/c5qi00240k }}</ref> Unlike natural enzymes, nanozymes offer stability, multifunctionality, and scalability.<ref name="auto"/>

=== Development and key milestones === Early discoveries in the 1990s included fullerene derivatives mimicking superoxide dismutase (SOD).<ref>{{cite journal |last1=Dugan |first1=Laura L. |last2=Gabrielsen |first2=Joseph K. |last3=Yu |first3=Shan P. |last4=Lin |first4=Tien-Sung |last5=Choi |first5=Dennis W. |s2cid=26139075 |title=Buckminsterfullerenol Free Radical Scavengers Reduce Excitotoxic and Apoptotic Death of Cultured Cortical Neurons |journal=Neurobiology of Disease |date=April 1996 |volume=3 |issue=2 |pages=129–135 |doi=10.1006/nbdi.1996.0013 |pmid=9173920 }}</ref> The 2000s saw the term "nanozyme" formalized and applications expand, such as nanoceria preventing retinal degeneration<ref>{{cite journal |last1=Chen |first1=Junping |last2=Patil |first2=Swanand |last3=Seal |first3=Sudipta |last4=McGinnis |first4=James F. |title=Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxides |journal=Nature Nanotechnology |date=29 October 2006 |volume=1 |issue=2 |pages=142–150 |doi=10.1038/nnano.2006.91 |pmid=18654167 |bibcode=2006NatNa...1..142C |s2cid=3093558 |url=https://stars.library.ucf.edu/facultybib2000/4664 }}</ref> and peroxidase-like activity in ferromagnetic nanoparticles for immunoassays.<ref>{{cite journal |last1=Gao |first1=Lizeng |last2=Zhuang |first2=Jie |last3=Nie |first3=Leng |last4=Zhang |first4=Jinbin |last5=Zhang |first5=Yu |last6=Gu |first6=Ning |last7=Wang |first7=Taihong |last8=Feng |first8=Jing |last9=Yang |first9=Dongling |last10=Perrett |first10=Sarah |last11=Yan |first11=Xiyun |title=Intrinsic peroxidase-like activity of ferromagnetic nanoparticles |journal=Nature Nanotechnology |date=26 August 2007 |volume=2 |issue=9 |pages=577–583 |doi=10.1038/nnano.2007.260 |pmid=18654371 |bibcode=2007NatNa...2..577G |s2cid=10602418 }}</ref>

The 2010s brought numerous reviews and applications, including colorimetric assays,<ref>{{cite journal |last1=Wei |first1=Hui |last2=Wang |first2=Erkang |title=Fe₃O₄ Magnetic Nanoparticles as Peroxidase Mimetics and Their Applications in H₂O₂ and Glucose Detection |journal=Analytical Chemistry |date=March 2008 |volume=80 |issue=6 |pages=2250–2254 |doi=10.1021/ac702203f |pmid=18290671 |bibcode=2008AnaCh..80.2250W }}</ref> tumor visualization,<ref>{{cite journal |last1=Fan |first1=Kelong |last2=Cao |first2=Changqian |last3=Pan |first3=Yongxin |last4=Lu |first4=Di |last5=Yang |first5=Dongling |last6=Feng |first6=Jing |last7=Song |first7=Lina |last8=Liang |first8=Minmin |last9=Yan |first9=Xiyun |title=Magnetoferritin nanoparticles for targeting and visualizing tumour tissues |journal=Nature Nanotechnology |date=17 June 2012 |volume=7 |issue=7 |pages=459–464 |doi=10.1038/nnano.2012.90 |pmid=22706697 |bibcode=2012NatNa...7..459F |s2cid=19859273 }}</ref> and anti-biofouling.<ref>{{cite journal |last1=Natalio |first1=Filipe |last2=André |first2=Rute |last3=Hartog |first3=Aloysius F. |last4=Stoll |first4=Brigitte |last5=Jochum |first5=Klaus Peter |last6=Wever |first6=Ron |last7=Tremel |first7=Wolfgang |title=Vanadium pentoxide nanoparticles mimic vanadium haloperoxidases and thwart biofilm formation |journal=Nature Nanotechnology |date=1 July 2012 |volume=7 |issue=8 |pages=530–535 |doi=10.1038/nnano.2012.91 |pmid=22751222 |bibcode=2012NatNa...7..530N }}</ref> Key books and reviews emerged, summarizing progress.<ref>{{cite book |last1=Wang |first1=Xiaoyu |last2=Guo |first2=Wenjing |last3=Hu |first3=Yihui |last4=Wu |first4=Jiangjiexing |last5=Wei |first5=Hui |title=Nanozymes: Next Wave of Artificial Enzymes |date=2016 |publisher=Springer |isbn=978-3-662-53068-9 }}</ref><ref name="pmid30534770" />

In the 2020s, nanozymes advanced in therapeutic applications, such as single-atom nanozymes for sepsis<ref>{{cite journal |last1=Cao |first1=Fangfang |last2=Zhang |first2=Lu |last3=You |first3=Yawen |last4=Zheng |first4=Lirong |last5=Ren |first5=Jinsong |last6=Qu |first6=Xiaogang |title=An Enzyme-Mimicking Single-Atom Catalyst as an Efficient Multiple Reactive Oxygen and Nitrogen Species Scavenger for Sepsis Management |journal=Angewandte Chemie |date=12 February 2020 |volume=132 |issue=13 |pages=5146–5153 |doi=10.1002/ange.201912182 |bibcode=2020AngCh.132.5146C |s2cid=214232731 }}</ref> and tumor therapy.<ref>{{cite journal |last1=Wang |first1=Dongdong |last2=Wu |first2=Huihui |last3=Phua |first3=Soo Zeng Fiona |last4=Yang |first4=Guangbao |last5=Qi Lim |first5=Wei |last6=Gu |first6=Long |last7=Qian |first7=Cheng |last8=Wang |first8=Haibao |last9=Guo |first9=Zhen |last10=Chen |first10=Hongzhong |last11=Zhao |first11=Yanli |title=Self-assembled single-atom nanozyme for enhanced photodynamic therapy treatment of tumor |journal=Nature Communications |date=17 January 2020 |volume=11 |issue=1 |page=357 |doi=10.1038/s41467-019-14199-7 |pmid=31953423 |pmc=6969186 |bibcode=2020NatCo..11..357W }}</ref> Strategies like data-informed discovery<ref>{{cite journal | last1=Li | first1=Sirong | last2=Zhou | first2=Zijun | last3=Tie | first3=Zuoxiu | last4=Wang | first4=Bing | last5=Ye | first5=Meng | last6=Du | first6=Lei | last7=Cui | first7=Ran | last8=Liu | first8=Wei | last9=Wan | first9=Cuihong | last10=Liu | first10=Quanyi | last11=Zhao | first11=Sheng | last12=Wang | first12=Quan | last13=Zhang | first13=Yihong | last14=Zhang | first14=Shuo | last15=Zhang | first15=Huigang | last16=Du | first16=Yan | last17=Wei | first17=Hui | title=Data-informed discovery of hydrolytic nanozymes | journal=Nature Communications | date=2022 | volume=13 | issue=1 | article-number=827 | doi=10.1038/s41467-022-28344-2 | pmid=35149676 | bibcode=2022NatCo..13..827L | pmc=8837776 }}</ref> and machine learning aided discovery,<ref>{{cite journal |last1=Wei |first1=Yonghua |last2=Wu |first2=Jin |last3=Wu |first3=Yixuan |last4=Liu |first4=Hongjiang |last5=Meng |first5=Fanqiang |last6=Liu |first6=Qiqi |last7=Midgley |first7=Adam C. |last8=Zhang |first8=Xiangyun |last9=Qi |first9=Tianyi |last10=Kang |first10=Helong |last11=Chen |first11=Rui |last12=Kong |first12=Deling |last13=Zhuang |first13=Jie |last14=Yan |first14=Xiyun |last15=Huang |first15=Xinglu |title=Prediction and Design of Nanozymes using Explainable Machine Learning |journal=Advanced Materials |date=2022 |volume=34 |issue=27 |article-number=e2201736 |doi=10.1002/adma.202201736 |pmid=35487518 |bibcode=2022AdM....3401736W |s2cid=248451764 }}</ref> and applications in treating conditions like Parkinson's disease, inflammatory bowel disease, stroke and traumatic brain injury were reported.<ref>{{cite journal |last1=Singh |first1=Namrata |last2=Savanur |first2=Mohammed Azharuddin |last3=Srivastava |first3=Shubhi |last4=D'Silva |first4=Patrick |last5=Mugesh |first5=Govindasamy |title=A Redox Modulatory Mn3O4 Nanozyme with Multi-Enzyme Activity Provides Efficient Cytoprotection to Human Cells in a Parkinson's Disease Model |journal=Angewandte Chemie International Edition |date=6 November 2017 |volume=56 |issue=45 |pages=14267–14271 |doi=10.1002/anie.201708573 |pmid=28922532 |bibcode=2017ACIE...5614267S }}</ref><ref>{{cite journal |last1=Zhao |first1=Shuai |last2=Duan |first2=Hongxia |last3=Yang |first3=Yili |last4=Yan |first4=Xiyun |last5=Fan |first5=Kelong |title=Fenozyme Protects the Integrity of the Blood–Brain Barrier against Experimental Cerebral Malaria |journal=Nano Letters |date=November 2019 |volume=19 |issue=12 |pages=8887–8895 |doi=10.1021/acs.nanolett.9b03774 |pmid=31671939 |bibcode=2019NanoL..19.8887Z |s2cid=207815491 }}</ref><ref>{{cite journal | vauthors = Yang Y, Li Z, Fan X, Jiang C, Wang J, Rastegar-Kashkooli Y, Wang TJ, Wang J, Wang M, Cheng N, Yuan X, Chen X, Jiang B, Wang J | title = Nanozymes: Potential Therapies for Reactive Oxygen Species Overproduction and Inflammation in Ischemic Stroke and Traumatic Brain Injury | journal = ACS Nano | volume = 18 | issue = 26 | pages = 16450–16467 | date = July 2024 | pmid = 38897929 | doi = 10.1021/acsnano.4c03425 | bibcode = 2024ACSNa..1816450Y }}</ref> Nanozymes were recognized as one of IUPAC's Top Ten Emerging Technologies in Chemistry in 2022.<ref>{{Cite web|url=https://iupac.org/iupac-2022-top-ten/|title=IUPAC Announces the 2022 Top Ten Emerging Technologies in Chemistry|first=Fabienne|last=Meyers|date=October 17, 2022|website=IUPAC &#124; International Union of Pure and Applied Chemistry}}</ref> Nanozyme is among the Top 10 Emerging Technologies of 2025 Summer Davos.<ref>{{Cite web|url=https://www.weforum.org/stories/2025/06/top-10-emerging-technologies-of-2025/|title=These are the top 10 emerging technologies of 2025|website=World Economic Forum}}</ref> A monograph entitled nanozymes was published in Chinese (《纳米酶》).<ref>{{cite web | title=《纳米酶》中文专著出版预告！邀您共赴开卷之约 | url=https://mp.weixin.qq.com/s/ZcjrFghDz2umTx0wX0vErg }}</ref>

== See also == * Abzyme: Antibodies can act as enzymes if they are selected against transition state analogues. Abzymes have a low K_M, meaning that they readily bind a target molecule, but have low V_max values, indicating a slow reaction rate. * Biomimetics * Bioorthogonal chemistry * Catalysis * Density functional theory * Directed evolution * Enzyme * Molecular machine * Molecularly imprinted polymer * Nanochemistry * Supramolecular chemistry * Synzyme * Zeolite

== References == {{reflist}}

===Bibliography=== * {{cite journal |author=Wiseman A |title=Designer enzyme and cell applications in industry and in environmental monitoring |journal=J Chem Technol Biotechnol |volume=56 |issue=1 |pages=3–13 |year=1993 |doi=10.1002/jctb.280560103 |pmid=7763363 |bibcode=1993JCTB...56....3W }} * {{cite journal |vauthors=Diekmann S, Weston J, Anders E, etal |title=Metal-mediated reactions modeled after nature |journal=J. Biotechnol. |volume=90 |issue=2 |pages=73–94 |date=April 2002 |pmid=12069195 |doi= 10.1016/s1389-0352(01)00067-8}}

Category:Enzymes Category:Synthetic biology Category:Nanotechnology