Please wait a minute...

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  2023, Vol. 43 Issue (10): 72-84    DOI: 10.13523/j.cb.2304002
综述     
人工金属酶研究进展*
刘小妍**,黄超群**,金雪芮,罗云孜***()
天津大学化工学院 教育部合成生物学前沿科学中心 系统生物工程教育部重点实验室 天津 300072
Research Progress of Artificial Metalloenzymes
LIU Xiao-yan**,HUANG Chao-qun**,JIN Xue-rui,LUO Yun-zi***()
Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
 全文: PDF(1490 KB)   HTML
摘要：

金属酶由金属辅因子和蛋白骨架构成。金属辅因子提供催化活性,是金属酶发挥功能的关键,而蛋白骨架为金属辅因子提供附着位点,同时提供手性环境。天然金属酶种类较多,可催化羟基化、环氧化等反应,其辅因子主要以金属离子或金属配体的形式存在,所含金属元素以Fe、Cu、Zn居多,部分天然金属酶也含Mn等金属元素。然而,由于天然金属酶难以催化非天然底物,且部分金属酶体外催化效率低、自身稳定性较差,无法得以广泛应用。近年来研究发现,通过对起催化功能的金属辅因子和提供酶促反应微环境的蛋白骨架进行理性设计构建人工金属酶(artificial metalloenzymes,ArMs),可提高金属酶的催化效率或使其能够催化多种天然和非天然反应。此外,利用纳米技术修饰人工金属酶可以提高金属酶的稳定性和可调控性,为人工金属酶的优化提供了新思路。总结近年来人工金属酶领域取得的成果,着重介绍构建人工金属酶策略方面的研究进展,包括金属辅因子的改造、蛋白骨架的设计、基于纳米技术的修饰等,并展望了设计改造人工金属酶所面临的机遇和挑战,以期为人工金属酶的设计和应用提供参考。
关键词： 人工金属酶;  辅因子;  蛋白骨架;  理性设计;  纳米技术    
Abstract:

Enzymes with high efficiency and specificity have attracted much attention from researchers. Among them, metalloenzymes account for about 1/3 of natural enzymes. Metalloenzymes are generally composed of metal cofactors and corresponding protein scaffolds, in which the metal cofactors provide the active center. The protein scaffolds provide the chiral environment and attachment sites for metal cofactors. Existing studies have revealed that metalloenzymes fail to work without metal cofactors. The metal cofactors mainly exist in the form of metal ions or metal ligands. Among the natural metalloenzymes discovered so far, the metal elements in metal cofactors are mainly Fe, Cu, and Zn. Besides, there are also Mn and other metal elements. Metalloenzymes play an important role in organisms, including signal transduction and immune regulation. Various metalloenzymes can catalyze different reactions, such as hydroxylation and epoxidation. However, it is difficult for natural metalloenzymes to catalyze nonnatural substrates. Some metalloenzymes have low catalytic efficiency and poor stability in vitro, making them unable to be widely used. Recently, rapidly developed biotechnology has accelerated the development of metalloenzymes. By simulating natural metalloenzymes, artificial metalloenzymes (ArMs) have been constructed continuously. The appearance of ArMs has expanded reaction types. In summary, three main strategies have been applied in designing ArMs, including the reconstruction of cofactors, design of protein scaffolds, and modification of nanoparticles. The reconstruction of cofactors is mainly achieved by chemical modification and replacement. Design of protein scaffolds is achieved by selecting some stable structures and utilizing computer-aided methods. Notably, the development of nanotechnology has also provided good ideas for redesigning ArMs. The enzyme property can be improved by binding metalloenzymes to the surface of nanometers or being embedded in nanoparticles. Herein, we summarize some achievements of ArMs in recent years. A brief introduction about the challenges and opportunities faced by ArMs is provided, which is helpful for the design and application of ArMs.
Key words: Artificial metalloenzyme    Cofactor    Protein scaffold    Rational design    Nanotechnology
收稿日期: 2023-04-03 出版日期: 2023-11-02
ZTFLH:  Q814  
基金资助: *国家重点研发计划(2018YFA0903300);国家自然科学基金(32071426)
通讯作者: ***电子信箱:luoyunzi827@aliyun.com   
作者简介: **具有同等贡献
服务　　
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章　　
刘小妍
黄超群
金雪芮
罗云孜

引用本文:

刘小妍, 黄超群, 金雪芮, 罗云孜. 人工金属酶研究进展*[J]. 中国生物工程杂志, 2023, 43(10): 72-84.

LIU Xiao-yan, HUANG Chao-qun, JIN Xue-rui, LUO Yun-zi. Research Progress of Artificial Metalloenzymes. China Biotechnology, 2023, 43(10): 72-84.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2304002    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I10/72

图1  人工金属酶的构建策略
图2  利用卟啉替换构建人工金属酶[27]
蛋白骨架 原辅因子 新辅因子 功能 参考文献
Apo-SiRCcP.1 - [4Fe-4S] 催化亚硫酸盐的还原反应 [11]
HSA - Au 催化氢胺化反应 [38]
Homo-oligomeric protein - Cu(bpy) 催化多质子/电子介导的氧化还原反应 [39]
MC6*a - Fe、Mn 过加氧酶活性 [40]
αRepA3 - Cu(II) 催化Diels-Alder反应 [41]
αRep - Co(III)-porphyrin complex 光诱导制氢和二氧化碳还原反应 [42]
MDRs - Cu(II)、BpyA_Cu(II) 催化Friedel-Crafts烷基化 [43]
mAbs - BIQ-Cu、BIQ-PdCl2、BIQ-Pd(OAc)2、
BIQ-PtCl2		 催化Friedel-Crafts烷基化反应 [44]
LmrR - Fe(III)-CPPIX 催化环丙烷化反应 [45]
LmrR - Cu(II)-phen complex 催化Friedel-Crafts烷基化反应 [46]
LmrR - Cu(II)-phenanthroline complex 催化Friedel- Crafts烷基化和
Diels - Alder反应		 [47]
LmrR - Cu(II) complexes 催化迈克尔加成反应 [48]
Sav-SOD - Cp*Ir(biot-p-L)Cl 催化不对称氢转移反应 [49]
Nitrobindin (NB) - Cp*Rh(III) complexes 催化环加成反应 [50]
Nitrobindin (NB) - Cp*Rh(III)-dithiophosphate complex 催化环加成反应 [51]
POP - Dirhodium complexes 催化环丙烷化反应 [52]
POP - Ru(II) polypyridyl complexes 催化环加成反应 [53]
POP - Dirhodium complexes 催化重氮化偶合反应 [54]
(A3A3’)Y26C - Mn (III)-tetraphenylporphyrin 过氧化物酶和单加氧酶的活性 [55]
Four-helix bundle - Zn-PPIX 过氧化物酶活性 [56]
Four-helix bundle - Ru(II)(η6-arene)(bipyridine) complexes 催化氢转移反应 [57]
Van and DADA complexes - [IrCp*(m-I)Cl]Cl 催化环亚胺的不对称加氢反应 [58]
Heptapeptidic - Methyl salicylate Pd complexes 催化去炔丙基化和Suzuki - Miyaura
交叉偶联反应		 [59]
TbADH Zn (II) Cp*Rh(III) complexes 催化还原反应 [24]
Azurin Cu Ni 催化碳碳耦合及硫酯合成反应 [60]
P450-BM3 Fe-PPIX Ir(Me)-deuteroporphyrin IX 催化烯烃环丙烷化反应 [61]
CYP119 Fe-PPIX Ir(Me)-PIX、Ir(Me)-MPIX 催化环丙烷化反应 [28,37,62]
Mb Fe-PPIX Fe-2, 4-diacetyl deuteroporphyrin IX 催化烯烃的不对称环丙烷化 [63]
Mb Fe-PPIX CuCP DNA切割活性 [64]
表1  含金属辅因子的人工金属酶
图3  利用蛋白支架构建人工金属酶[70]
图4  从头设计人工金属酶
图5  利用纳米技术辅助修饰人工金属酶
[1] Lin Y W. Rational design of artificial metalloproteins and metalloenzymes with metal clusters. Molecules, 2019, 24(15): 2743.
doi: 10.3390/molecules24152743
[2] Riordan J F, Vallee B L. The functional roles of metals in metalloenzymes. Advances in Experimental Medicine and Biology, 1974, 48(0): 33-57.
pmid: 4215300
[3] Karlin K D. Metalloenzymes, structural motifs, and inorganic models. Science, 1993, 261(5122): 701-708.
pmid: 7688141
[4] Lovelock S L, Crawshaw R, Basler S, et al. The road to fully programmable protein catalysis. Nature, 2022, 606(7912): 49-58.
doi: 10.1038/s41586-022-04456-z
[5] Bush K. Recent developments in β-lactamase research and their implications for the future. Reviews of Infectious Diseases, 1988, 10(4): 681-690.
pmid: 3055169
[6] 陈姣, 郑珩, 沈秉正, 等. IMP型金属β-内酰胺酶及其抑制剂研究进展. 今日药学, 2010, 20(9): 1-5.
Chen J, Zheng H, Shen B Z, et al. Research progress of IMP-type metal β-lactamase and its inhibitors. Pharmacy Today, 2010, 20(9): 1-5.
[7] 王继乾, 闫宏宇, 李洁, 等. 基于多肽自组装的人工金属酶. 化学进展, 2018, 30(8): 1121-1132.
doi: 10.7536/PC180112
Wang J Q, Yan H Y, Li J, et al. Artificial metalloenzymes based on peptide self-assembly. Progress in Chemistry, 2018, 30(8): 1121-1132.
doi: 10.7536/PC180112
[8] Yamamura K, Kaiser E T. Studies on the oxidase activity of copper(II) carboxypeptidase A. Journal of the Chemical Society, Chemical Communications, 1976, 20: 830-831.
[9] Schwizer F, Okamoto Y, Heinisch T, et al. Artificial metalloenzymes: reaction scope and optimization strategies. Chemical Reviews, 2018, 118(1): 142-231.
doi: 10.1021/acs.chemrev.7b00014 pmid: 28714313
[10] Thompson Z, Cowan J A. Artificial metalloenzymes: recent developments and innovations in bioinorganic catalysis. Small, 2020, 16(27): e2000392.
[11] Mirts E N, Petrik I D, Hosseinzadeh P, et al. A designed heme-[4Fe-4S]metalloenzyme catalyzes sulfite reduction like the native enzyme. Science, 2018, 361(6407): 1098-1101.
doi: 10.1126/science.aat8474 pmid: 30213908
[12] Bragança P M S, Carepo M S P, Pauleta S R, et al. Incorporation of a molybdenum atom in a rubredoxin-type centre of a de novo-designed α3DIV-L21C three-helical bundle peptide. Journal of Inorganic Biochemistry, 2023, 240: 112096.
doi: 10.1016/j.jinorgbio.2022.112096
[13] Nastri F, Chino M, Maglio O, et al. Design and engineering of artificial oxygen-activating metalloenzymes. Chemical Society Reviews, 2016, 45(18): 5020-5054.
doi: 10.1039/c5cs00923e pmid: 27341693
[14] Doble M V, Ward A C C, Deuss P J, et al. Catalyst design in oxidation chemistry; from KMnO4 to artificial metalloenzymes. Bioorganic & Medicinal Chemistry, 2014, 22(20): 5657-5677.
doi: 10.1016/j.bmc.2014.07.002
[15] 王志鹏, 邓耿. 基于辅因子化学本质及功能的分类与讨论. 大学化学, 2016, 31(4): 39-48.
Wang Z P, Deng G. Discussion and classification of cofactors based on their chemical essences and functions. University Chemistry, 2016, 31(4): 39-48.
[16] Bersellini M, Roelfes G. A metal ion regulated artificial metalloenzyme. Dalton Transactions, 2017, 46(13): 4325-4330.
doi: 10.1039/C7DT00533D
[17] Alonso-Cotchico L, Rodríguez-Guerra Pedregal J, Lledós A, et al. The effect of cofactor binding on the conformational plasticity of the biological receptors in artificial metalloenzymes: the case study of LmrR. Frontiers in Chemistry, 2019, 7: 211.
doi: 10.3389/fchem.2019.00211 pmid: 31024897
[18] Hu C, Yu Y, Wang J Y. Improving artificial metalloenzymes’ activity by optimizing electron transfer. Chemical Communications, 2017, 53(30): 4173-4186.
doi: 10.1039/C6CC09921A
[19] Oohora K, Onoda A, Hayashi T. Hemoproteins reconstituted with artificial metal complexes as biohybrid catalysts. Accounts of Chemical Research, 2019, 52(4): 945-954.
doi: 10.1021/acs.accounts.8b00676 pmid: 30933477
[20] Fruk L, Müller J, Niemeyer C M. Kinetic analysis of semisynthetic peroxidase enzymes containing a covalent DNA-heme adduct as the cofactor. Chemistry, 2006, 12(28): 7448-7457.
[21] Hayashi T, Hitomi Y, Ando T, et al. Peroxidase activity of myoglobin is enhanced by chemical mutation of heme-propionates. Journal of the American Chemical Society, 1999, 121(34): 7747-7750.
doi: 10.1021/ja9841005
[22] Mirts E N, Bhagi-Damodaran A, Lu Y. Understanding and modulating metalloenzymes with unnatural amino acids, non-native metal ions, and non-native metallocofactors. Accounts of Chemical Research, 2019, 52(4): 935-944.
doi: 10.1021/acs.accounts.9b00011 pmid: 30912643
[23] Ohashi M, Koshiyama T, Ueno T, et al. Preparation of artificial metalloenzymes by insertion of chromium(III) schiff base complexes into apomyoglobin mutants. Angewandte Chemie, 2003, 42(9): 1005-1008.
[24] Morra S, Pordea A. Biocatalyst-artificial metalloenzyme cascade based on alcohol dehydrogenase. Chemical Science, 2018, 9(38): 7447-7454.
doi: 10.1039/c8sc02371a pmid: 30319745
[25] Sreenilayam G, Moore E J, Steck V, et al. Metal substitution modulates the reactivity and extends the reaction scope of myoglobin carbene transfer catalysts. Advanced Synthesis & Catalysis, 2017, 359(12): 2076-2089.
[26] Deng Y L, Dwaraknath S, Ouyang W H O, et al. Engineering an oxygen-binding protein for photocatalytic CO2 reductions in water. Angewandte Chemie, 2023, 135(20): e202215719.
doi: 10.1002/ange.v135.20
[27] Dydio P, Key H M, Nazarenko A, et al. An artificial metalloenzyme with the kinetics of native enzymes. Science, 2016, 354(6308): 102-106.
pmid: 27846500
[28] Liu Z N, Huang J, Gu Y, et al. Assembly and evolution of artificial metalloenzymes within E. coli Nissle 1917 for enantioselective and site-selective functionalization of C-H and C=C bonds. Journal of the American Chemical Society, 2022, 144(2): 883-890.
doi: 10.1021/jacs.1c10975
[29] Perkins L J, Weaver B R, Buller A R, et al. De novo biosynthesis of a nonnatural cobalt porphyrin cofactor in E. coli and incorporation into hemoproteins. Proceedings of the National Academy of Sciences of the United States of America, 2021, 118(16): e2017625118.
[30] 林英武. 人工金属酶分子设计新进展: 肌红蛋白研究实例分析. 化学进展, 2018, 30(10): 1464-1474.
doi: 10.7536/PC180528
Lin Y W. Rational design of artificial metalloenzymes: case studies in myoglobin. Progress in Chemistry, 2018, 30(10): 1464-1474.
doi: 10.7536/PC180528
[31] Bhagi-Damodaran A, Michael M A, Zhu Q H, et al. Why copper is preferred over iron for oxygen activation and reduction in haem-copper oxidases. Nature Chemistry, 2017, 9(3): 257-263.
doi: 10.1038/nchem.2643 pmid: 28221360
[32] Hosseinzadeh P, Marshall N M, Chacón K N, et al. Design of a single protein that spans the entire 2-V range of physiological redox potentials. Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(2): 262-267.
[33] Sreenilayam G, Moore E J, Steck V, et al. Stereoselective olefin cyclopropanation under aerobic conditions with an artificial enzyme incorporating an iron-chlorin e6 cofactor. ACS Catalysis, 2017, 7(11): 7629-7633.
doi: 10.1021/acscatal.7b02583 pmid: 29576911
[34] Carminati D M, Moore E J, Fasan R D. Strategies for the expression and characterization of artificial myoglobin-based carbene transferases. Methods in Enzymology, 2020, 644: 35-61.
doi: S0076-6879(20)30282-2 pmid: 32943150
[35] 袁飞燕, 于洋, 李春. 基于非天然结构组件的人工酶设计与应用. 合成生物学, 2020, 1(6): 685-696.
doi: 10.12211/2096-8280.2020-008
Yuan F Y, Yu Y, Li C. Artificial enzyme designs and its application based on non-natural structural elements. Synthetic Biology Journal, 2020, 1(6): 685-696.
doi: 10.12211/2096-8280.2020-008
[36] Oohora K, Hayashi T. Myoglobins engineered with artificial cofactors serve as artificial metalloenzymes and models of natural enzymes. Dalton Transactions, 2021, 50(6): 1940-1949.
doi: 10.1039/D0DT03597A
[37] Gu Y, Natoli S N, Liu Z N, et al. Site-selective functionalization of (sp3)C-H bonds catalyzed by artificial metalloenzymes containing an iridium-porphyrin cofactor. Angewandte Chemie, 2019, 58(39): 13954-13960.
[38] Chang T C, Vong K, Yamamoto T, et al. Prodrug activation by gold artificial metalloenzyme-catalyzed synthesis of phenanthridinium derivatives via hydroamination. Angewandte Chemie, 2021, 60(22): 12446-12454.
[39] Jung S M, Yang M W, Song W J. Symmetry-adapted synthesis of dicopper oxidases with divergent dioxygen reactivity. Inorganic Chemistry, 2022, 61(31): 12433-12441.
doi: 10.1021/acs.inorgchem.2c01898
[40] Leone L, D’Alonzo D, Balland V, et al. Mn-mimochrome VI*a: an artificial metalloenzyme with peroxygenase activity. Frontiers in Chemistry, 2018, 6: 590.
doi: 10.3389/fchem.2018.00590
[41] Di Meo T, Ghattas W, Herrero C, et al. αRep A3: a versatile artificial scaffold for metalloenzyme design. Chemistry, 2017, 23(42): 10156-10166.
[42] Udry G A O, Tiessler-Sala L, Pugliese E, et al. Photocatalytic hydrogen production and carbon dioxide reduction catalyzed by an artificial cobalt hemoprotein. International Journal of Molecular Sciences, 2022, 23(23): 14640.
doi: 10.3390/ijms232314640
[43] Bersellini M, Roelfes G. Multidrug resistance regulators (MDRs) as scaffolds for the design of artificial metalloenzymes. Organic & Biomolecular Chemistry, 2017, 15(14): 3069-3073.
[44] Adachi T, Harada A, Yamaguchi H. Atroposelective antibodies as a designed protein scaffold for artificial metalloenzymes. Scientific Reports, 2019, 9(1): 13551.
doi: 10.1038/s41598-019-49844-0 pmid: 31537832
[45] Villarino L, Splan K E, Reddem E, et al. An artificial heme enzyme for cyclopropanation reactions. Angewandte Chemie, 2018, 57(26): 7785-7789.
[46] Villarino L, Chordia S, Alonso-Cotchico L, et al. Cofactor binding dynamics influence the catalytic activity and selectivity of an artificial metalloenzyme. ACS Catalysis, 2020, 10(20): 11783-11790.
doi: 10.1021/acscatal.0c01619 pmid: 33101759
[47] Chordia S, Narasimhan S, Paioni A L, et al. In vivo assembly of artificial metalloenzymes and application in whole-cell biocatalysis. Angewandte Chemie, 2021, 60(11): 5913-5920.
[48] Zhou Z, Roelfes G. Synergistic catalysis in an artificial enzyme by simultaneous action of two abiological catalytic sites. Nature Catalysis, 2020, 3(3): 289-294.
doi: 10.1038/s41929-019-0420-6
[49] Igareta N V, Tachibana R, Spiess D C, et al. Spiers memorial lecture: shielding the active site: a streptavidin superoxide-dismutase chimera as a host protein for asymmetric transfer hydrogenation. Faraday Discussions, 2023, 244(0):9-20.
doi: 10.1039/d3fd00034f pmid: 36924204
[50] Kato S, Onoda A, Grimm A R, et al. Incorporation of a Cp*Rh(III)-dithiophosphate cofactor with latent activity into a protein scaffold generates a biohybrid catalyst promoting C(sp2)-H bond functionalization. Inorganic Chemistry, 2020, 59(19): 14457-14463.
doi: 10.1021/acs.inorgchem.0c02245
[51] Kato S, Onoda A, Grimm A R, et al. Construction of a whole-cell biohybrid catalyst using a Cp*Rh(III)-dithiophosphate complex as a precursor of a metal cofactor. Journal of Inorganic Biochemistry, 2021, 216: 111352.
doi: 10.1016/j.jinorgbio.2020.111352
[52] Lewis J C. Beyond the second coordination sphere: engineering dirhodium artificial metalloenzymes to enable protein control of transition metal catalysis. Accounts of Chemical Research, 2019, 52(3): 576-584.
doi: 10.1021/acs.accounts.8b00625 pmid: 30830755
[53] Zubi Y S, Liu B Q, Gu Y F, et al. Controlling the optical and catalytic properties of artificial metalloenzyme photocatalysts using chemogenetic engineering. Chemical Science, 2022, 13(5): 1459-1468.
doi: 10.1039/d1sc05792h pmid: 35222930
[54] Upp D M, Huang R, Li Y, et al. Engineering dirhodium artificial metalloenzymes for diazo coupling cascade reactions. Angewandte Chemie, 2021, 60(44): 23672-23677.
[55] Kariyawasam K, Di Meo T, Hammerer F, et al. An artificial hemoprotein with inducible peroxidase- and monooxygenase-like activities. Chemistry, 2020, 26(65): 14929-14937.
[56] Curnow P, Hardy B J, Dufour V, et al. Small-residue packing motifs modulate the structure and function of a minimal de novo membrane protein. Scientific Reports, 2020, 10(1): 15203.
doi: 10.1038/s41598-020-71585-8 pmid: 32938984
[57] Biggs G S, Klein O J, Maslen S L, et al. Controlled ligand exchange between ruthenium organometallic cofactor precursors and a Naïve protein scaffold generates artificial metalloenzymes catalysing transfer hydrogenation. Angewandte Chemie, 2021, 60(19): 10919-10927.
[58] Facchetti G, Bucci R, Fusè M, et al. Alternative strategy to obtain artificial imine reductase by exploiting vancomycin/D-Ala-D-Ala interactions with an iridium metal complex. Inorganic Chemistry, 2021, 60(5): 2976-2982.
doi: 10.1021/acs.inorgchem.0c02969 pmid: 33550804
[59] Pérez-López A M, Belsom A, Fiedler L, et al. Dual-bioorthogonal catalysis by a palladium peptide complex. Journal of Medicinal Chemistry, 2023, 66(5): 3301-3311.
doi: 10.1021/acs.jmedchem.2c01689
[60] Manesis A C, Yerbulekova A, Shearer J, et al. Thioester synthesis by a designed nickel enzyme models prebiotic energy conversion. Proceedings of the National Academy of Sciences of the United States of America, 2022, 119(30): e2123022119.
[61] Reynolds E W, Schwochert T D, McHenry M W, et al. Orthogonal expression of an artificial metalloenzyme for abiotic catalysis. ChemBioChem, 2017, 18(24): 2380-2384.
doi: 10.1002/cbic.201700397 pmid: 29024391
[62] Huang J, Liu Z N, Bloomer B J, et al. Unnatural biosynthesis by an engineered microorganism with heterologously expressed natural enzymes and an artificial metalloenzyme. Nature Chemistry, 2021, 13(12): 1186-1191.
doi: 10.1038/s41557-021-00801-3 pmid: 34650235
[63] Carminati D M, Fasan R D. Stereoselective cyclopropanation of electron-deficient olefins with a cofactor redesigned carbene transferase featuring radical reactivity. ACS Catalysis, 2019, 9(10): 9683-9697.
doi: 10.1021/acscatal.9b02272 pmid: 32257582
[64] Dong Y, Chen Y M, Kong X J, et al. Rational design of an artificial hydrolytic nuclease by introduction of a sodium copper chlorophyllin in L29E myoglobin. Journal of Inorganic Biochemistry, 2022, 235: 111943.
doi: 10.1016/j.jinorgbio.2022.111943
[65] Jeong W J, Yu J, Song W J. Proteins as diverse, efficient, and evolvable scaffolds for artificial metalloenzymes. Chemical Communications, 2020, 56(67): 9586-9599.
doi: 10.1039/d0cc03137b pmid: 32691751
[66] Joh N H, Wang T, Bhate M P, et al. De novo design of a transmembrane Zn2+-transporting four-helix bundle. Science, 2014, 346(6216): 1520-1524.
doi: 10.1126/science.1261172
[67] Mann S I, Heinisch T, Ward T R, et al. Peroxide activation regulated by hydrogen bonds within artificial Cu proteins. Journal of the American Chemical Society, 2017, 139(48): 17289-17292.
doi: 10.1021/jacs.7b10452 pmid: 29117678
[68] Filice M, Romero O, Gutiérrez-Fernández J, et al. Synthesis of a heterogeneous artificial metallolipase with chimeric catalytic activity. Chemical Communications, 2015, 51(45): 9324-9327.
doi: 10.1039/c5cc02450a pmid: 25960359
[69] Fischer J, Renn D, Quitterer F, et al. Robust and versatile host protein for the design and evaluation of artificial metal centers. ACS Catalysis, 2019, 9(12): 11371-11380.
doi: 10.1021/acscatal.9b02896
[70] Roelfes G. LmrR: a privileged scaffold for artificial metalloenzymes. Accounts of Chemical Research, 2019, 52(3): 545-556.
doi: 10.1021/acs.accounts.9b00004 pmid: 30794372
[71] Bähr S, Brinkmann-Chen S, Garcia-Borràs M, et al. Selective enzymatic oxidation of silanes to silanols. Angewandte Chemie, 2020, 59(36): 15507-15511.
[72] Ensari Y, de Almeida Santos G, Ruff A J, et al. Engineered P450 BM3 and cpADH5 coupled cascade reaction for β-oxo fatty acid methyl ester production in whole cells. Enzyme and Microbial Technology, 2020, 138: 109555.
doi: 10.1016/j.enzmictec.2020.109555
[73] Beaumet M, Dose A, Bräuer A, et al. An artificial metalloprotein with metal-adaptive coordination sites and Ni-dependent quercetinase activity. Journal of Inorganic Biochemistry, 2022, 235: 111914.
doi: 10.1016/j.jinorgbio.2022.111914
[74] Kato S, Onoda A, Schwaneberg U, et al. Evolutionary engineering of a Cp*Rh(III) complex-linked artificial metalloenzyme with a chimeric β-barrel protein scaffold. Journal of the American Chemical Society, 2023, 145(15): 8285-8290.
[75] Alonso-Cotchico L, Rodríguez-Guerra J, Lledós A, et al. Molecular modeling for artificial metalloenzyme design and optimization. Accounts of Chemical Research, 2020, 53(4): 896-905.
doi: 10.1021/acs.accounts.0c00031 pmid: 32233391
[76] Martins F, Pordea A, Jäger C M. Computationally driven design of an artificial metalloenzyme using supramolecular anchoring strategies of iridium complexes to alcohol dehydrogenase. Faraday Discussions, 2022, 234: 315-335.
doi: 10.1039/d1fd00070e pmid: 35156975
[77] Sánchez-Aparicio J E, Sciortino G, Mates-Torres E, et al. Successes and challenges in multiscale modelling of artificial metalloenzymes: the case study of POP-Rh2 cyclopropanase. Faraday Discussions, 2022, 234: 349-366.
doi: 10.1039/d1fd00069a pmid: 35147145
[78] Basler S, Studer S, Zou Y K, et al. Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold. Nature Chemistry, 2021, 13(3): 231-235.
doi: 10.1038/s41557-020-00628-4
[79] Gutte B, Klauser S. Design of catalytic polypeptides and proteins. Protein Engineering, Design and Selection, 2018, 31(12): 457-470.
doi: 10.1093/protein/gzz009
[80] Reig A J, Pires M M, Snyder R A, et al. Alteration of the oxygen-dependent reactivity of de novo Due Ferri proteins. Nature Chemistry, 2012, 4(11): 900-906.
doi: 10.1038/nchem.1454
[81] Lombardi A, Pirro F, Maglio O, et al. De novo design of four-helix bundle metalloproteins: one scaffold, diverse reactivities. Accounts of Chemical Research, 2019, 52(5): 1148-1159.
doi: 10.1021/acs.accounts.8b00674 pmid: 30973707
[82] Pirro F, La Gatta S, Arrigoni F, et al. A de novo-designed type 3 copper protein tunes catechol substrate recognition and reactivity. Angewandte Chemie, 2023, 62(1): e202211552.
[83] Marcos E, Chidyausiku T M, McShan A C, et al. De novo design of a non-local β-sheet protein with high stability and accuracy. Nature Structural & Molecular Biology, 2018, 25(11): 1028-1034.
doi: 10.1038/s41594-018-0141-6
[84] Rufo C M, Moroz Y S, Moroz O V, et al. Short peptides self-assemble to produce catalytic amyloids. Nature Chemistry, 2014, 6(4): 303-309.
doi: 10.1038/nchem.1894 pmid: 24651196
[85] Cangelosi V, Ruckthong L, PecoraroV L, et al. Lead: its effects on environment and health. Berlin: De Gruyter, 2017: 271-318.
[86] Thomas F, Dawson W M, Lang E J M, et al. De novo-designed α-helical barrels as receptors for small molecules. ACS Synthetic Biology, 2018, 7(7): 1808-1816.
doi: 10.1021/acssynbio.8b00225 pmid: 29944338
[87] Koebke K J, Pecoraro V L. Development of de novo copper nitrite reductases: where we are and where we need to go. ACS Catalysis, 2018, 8(9): 8046-8057.
doi: 10.1021/acscatal.8b02153 pmid: 30294504
[88] Hassan I S, Fuller J T, Dippon V N, et al. Tuning through-space interactions via the secondary coordination sphere of an artificial metalloenzyme leads to enhanced Rh(iii)-catalysis. Chemical Science, 2022, 13(32): 9220-9224.
doi: 10.1039/d2sc03674f pmid: 36093000
[89] Li R F, Wijma H J, Song L, et al. Computational redesign of enzymes for regio- and enantioselective hydroamination. Nature Chemical Biology, 2018, 14(7): 664-670.
doi: 10.1038/s41589-018-0053-0 pmid: 29785057
[90] Pingale P, Kendre P, Pardeshi K, et al. An emerging era in manufacturing of drug delivery systems: nanofabrication techniques. Heliyon, 2023, 9(3): e14247.
doi: 10.1016/j.heliyon.2023.e14247
[91] Zambrano G, Ruggiero E, Malafronte A, et al. Artificial heme enzymes for the construction of gold-based biomaterials. International Journal of Molecular Sciences, 2018, 19(10): 2896.
doi: 10.3390/ijms19102896
[92] Wang D D, Jana D, Zhao Y L. Metal-organic framework derived nanozymes in biomedicine. Accounts of Chemical Research, 2020, 53(7): 1389-1400.
doi: 10.1021/acs.accounts.0c00268 pmid: 32597637
[93] Wang Q Q, Zhang X P, Huang L, et al. GOx@ZIF-8(NiPd) nanoflower: an artificial enzyme system for tandem catalysis. Angewandte Chemie, 2017, 56(50): 16082-16085.
[94] Wu X L, Yue H, Zhang Y Y, et al. Packaging and delivering enzymes by amorphous metal-organic frameworks. Nature Communications, 2019, 10(1): 5165.
doi: 10.1038/s41467-019-13153-x pmid: 31727883
[95] Song S X, Wang J Y, Song N, et al. Peptide interdigitation-induced twisted nanoribbons as chiral scaffolds for supramolecular nanozymes. Nanoscale, 2020, 12(4): 2422-2433.
doi: 10.1039/c9nr09492j pmid: 31916547
[96] Yuan G Y, Xi Z, Wang C, et al. Construction of supramolecular chiral polyaniline-gold nanocomposite as nanozyme for enantioselective catalysis. Acta Physico-Chimica Sinica, 2023, 39 (7): 2212061.
[97] Chen M, Wang Z H, Shu J X, et al. Mimicking a natural enzyme system: cytochrome c oxidase-like activity of Cu2O nanoparticles by receiving electrons from cytochrome c. Inorganic Chemistry, 2017, 56(16): 9400-9403.
doi: 10.1021/acs.inorgchem.7b01393
[98] Ganguly A, Luong T Q, Brylski O, et al. Elucidation of the catalytic mechanism of a miniature zinc finger hydrolase. The Journal of Physical Chemistry B, 2017, 121(26): 6390-6398.
doi: 10.1021/acs.jpcb.7b05027
[99] Hirota S, Lin Y W. Design of artificial metalloproteins/metalloenzymes by tuning noncovalent interactions. Journal of Biological Inorganic Chemistry, 2018, 23(1): 7-25.
doi: 10.1007/s00775-017-1506-8 pmid: 29218629
[100] Haga T, Hirakawa H, Nagamune T. Artificial self-sufficient cytochrome P450 containing multiple auxiliary proteins demonstrates improved monooxygenase activity. Biotechnology Journal, 2018, 13(12): e1800088.
[101] Yu H L, Li T, Chen F F, et al. Bioamination of alkane with ammonium by an artificially designed multienzyme cascade. Metabolic Engineering, 2018, 47: 184-189.
doi: 10.1016/j.ymben.2018.02.009
[102] Wang X L, Lin X D, Jiang Y P, et al. Engineering cytochrome P450BM3 enzymes for direct nitration of unsaturated hydrocarbons. Angewandte Chemie, 2023, 62(13): e202217678.
[103] 于洋, 王江云. 人工酶与定向进化的前沿与挑战. 科技导报, 2020, 38(8): 101-105.
Yu Y, Wang J Y. Frontiers and challenges of artificial enzyme and directed evolution. Science & Technology Review, 2020, 38(8): 101-105.
[104] Huang P S, Boyken S E, Baker D. The coming of age of de novo protein design. Nature, 2016, 537(7620): 320-327.
doi: 10.1038/nature19946
[105] Thomson A R, Wood C W, Burton A J, et al. Computational design of water-soluble α-helical barrels. Science, 2014, 346(6208): 485-488.
doi: 10.1126/science.1257452 pmid: 25342807
[106] Koga N, Tatsumi-Koga R, Liu G H, et al. Principles for designing ideal protein structures. Nature, 2012, 491(7423): 222-227.
doi: 10.1038/nature11600
[107] Pan X J, Thompson M C, Zhang Y, et al. Expanding the space of protein geometries by computational design of de novo fold families. Science, 2020, 369(6507): 1132-1136.
doi: 10.1126/science.abc0881
[108] Huang B, Xu Y, Hu X H, et al. A backbone-centred energy function of neural networks for protein design. Nature, 2022, 602(7897): 523-528.
doi: 10.1038/s41586-021-04383-5
[109] Morcos F, Pagnani A, Lunt B, et al. Direct-coupling analysis of residue coevolution captures native contacts across many protein families. Proceedings of the National Academy of Sciences of the United States of America, 2011, 108(49): E1293-E1301.
[110] Senior A W, Evans R, Jumper J, et al. Improved protein structure prediction using potentials from deep learning. Nature, 2020, 577(7792): 706-710.
doi: 10.1038/s41586-019-1923-7
[111] Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature, 2021, 596(7873): 583-589.
doi: 10.1038/s41586-021-03819-2
[112] Ferruz N, Heinzinger M, Akdel M, et al. From sequence to function through structure: deep learning for protein design. Computational and Structural Biotechnology Journal, 2022, 21: 238-250.
doi: 10.1016/j.csbj.2022.11.014
[113] Wang J, Lisanza S, Juergens D, et al. Scaffolding protein functional sites using deep learning. Science, 2022, 377(6604): 387-394.
doi: 10.1126/science.abn2100 pmid: 35862514
[1] 张鸿伟, 王鹏超. 微生物辅因子工程研究进展*[J]. 中国生物工程杂志, 2023, 43(4): 112-122.
[2] 苏影, 张炜坚, 万宇翔, 沈天放, 张欣然, 张如悦, 谭文松, 赵亮. CHO细胞强化流加培养过程理性设计与建立[J]. 中国生物工程杂志, 2023, 43(10): 20-31.
[3] 贾男,臧国伟,李春,王颖. 辅因子在微生物细胞工厂中的代谢调控与应用*[J]. 中国生物工程杂志, 2022, 42(7): 79-89.
[4] 魏子翔,张柳群,雷磊,韩正刚,杨江科. 疏棉状嗜热丝孢菌(Thermomyces lanuginosus)脂肪酶的理性设计提高其活性和温度稳定性[J]. 中国生物工程杂志, 2021, 41(2/3): 63-69.
[5] 闫伟欢,黄统,洪解放,马媛媛. 丁醇在大肠杆菌中的生物合成研究进展*[J]. 中国生物工程杂志, 2020, 40(9): 69-76.
[6] 李炳娟,刘金锭,廖谊芳,韩文英,刘珂,侯晨露,张磊. 老黄酶OYE家族的蛋白质工程的研究进展 *[J]. 中国生物工程杂志, 2020, 40(3): 163-169.
[7] 苏永君,胡蝶,胡博淳,李闯,文正,章晨,邬敏辰. 定点突变提高环氧化物水解酶AuEH2催化对甲基苯基缩水甘油醚的对映选择性*[J]. 中国生物工程杂志, 2020, 40(3): 88-95.
[8] 唐存多,史红玲,焦铸锦,刘飞,许建和,阚云超,姚伦广. CPC乙酰化酶底物结合区域Loop上脯氨酸对其催化特性的影响*[J]. 中国生物工程杂志, 2017, 37(12): 34-39.
[9] 虞晓丹, 吴秀秀, 姚冬生, 刘大岭, 谢春芳. 基于分子结构评价的Bacillus subtilis β-1,4-内切木聚糖酶胰蛋白酶抗性的理性设计[J]. 中国生物工程杂志, 2016, 36(8): 80-88.
[10] 郭超, 王志彦, 甘一如, 李丹, 邓勇, 于浩然, 黄鹤. 技术与方法理性设计改造牛肠激酶的热稳定性[J]. 中国生物工程杂志, 2016, 36(8): 46-54.
[11] 马晨露, 唐存多, 史红玲, 王瑞, 岳超, 夏敏, 邬敏辰, 阚云超. 头孢菌素C乙酰化酶的半理性改造及7-ACA的生物合成[J]. 中国生物工程杂志, 2015, 35(12): 65-71.
[12] 刘晓霏, 付晶, 霍广鑫, 章博, 王智文, 陈涛. 生物法制备平台化合物乙偶姻的最新研究进展[J]. 中国生物工程杂志, 2015, 35(10): 91-99.
[13] 唐存多, 史红玲, 唐青海, 焦铸锦, 阚云超, 邬敏辰, 李剑芳. 生物催化剂发现与改造的研究进展[J]. 中国生物工程杂志, 2014, 34(9): 113-121.
[14] 王大慧, 许宏庆, 汪成富, 卫功元. 酸胁迫在提升富硒/GSH产朊假丝酵母性能中的作用[J]. 中国生物工程杂志, 2013, 33(11): 81-85.
[15] 郭红光 吴海江 茆灿泉. 蛋白骨架在随机肽库构建及靶分子筛选中的应用[J]. 中国生物工程杂志, 2009, 29(09): 0-0.
主管：中国科学院 　主办：中国科学院文献情报中心 　中国生物技术发展中心 　中国生物工程学会