Advances in Engineering Strategies and Applications of Whole-Cell Artificial Metalloenzymes

ZHANG Yingjiao; LIU Xiaoyu; WANG Yunpeng; XIANG Lin; LI Chun; WANG Runming

doi:10.12211/2096-8280.2026-058

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Advances in Engineering Strategies and Applications of Whole-Cell Artificial Metalloenzymes

更新时间：2026-08-31

- Advances in Engineering Strategies and Applications of Whole-Cell Artificial Metalloenzymes
- 全细胞人工金属酶的工程化策略及应用研究
- Synthetic Biology Journal Pages: 1-19(2026)
- 作者机构：
  
  1.清华大学深圳国际研究生院生物医药与健康工程研究院，广东深圳 518055
  2.清华大学化工系，北京 100084
  3.北京理工大学化学与化工学院，北京 100101
  4.工业生物催化教育部重点实验室，北京 100084
  5.活性蛋白多肽绿色生物制造广东普通高校重点实验室，广东深圳 518055
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2026-058
  CLC： Q55
- Received：24 June 2026，
  
  Revised：2026-08-21，
  
  Online First：31 August 2026，
- 稿件说明：
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张英娇，刘晓宇，王云鹏，相林，李春，王润铭. 全细胞人工金属酶的工程化策略及应用研究［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-058

ZHANG Yingjiao， LIU Xiaoyu， WANG Yunpeng， XIANG Lin， LI Chun， WANG Runming. Advances in Engineering Strategies and Applications of Whole-Cell Artificial Metalloenzymes［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-058
张英娇，刘晓宇，王云鹏，相林，李春，王润铭. 全细胞人工金属酶的工程化策略及应用研究［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-058 DOI：

ZHANG Yingjiao， LIU Xiaoyu， WANG Yunpeng， XIANG Lin， LI Chun， WANG Runming. Advances in Engineering Strategies and Applications of Whole-Cell Artificial Metalloenzymes［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-058 DOI：

摘要

人工金属酶（Artificial metalloenzymes， ArMs）将非天然金属催化中心整合至蛋白质支架中，兼具金属催化剂的反应多样性和生物大分子的选择性识别能力，为拓展天然酶催化反应边界提供了重要工具。体外重构 ArMs 已在不对称转移氢化、不对称环丙烷化及 C-H 键不对称官能化等反应中展现出独特优势，但其进一步的应用仍受限于蛋白纯化成本高、催化体系稳定性不足等问题。将ArMs构建于活细胞或细胞衍生体系中，依托细胞代谢网络与保护机制，以及区室化结构等特点，提升了催化剂稳定性及生产效率；同时支持多步级联反应及高通量筛选，展现出工业化应用潜力。本文系统梳理了全细胞体系下ArMs的最新进展，核心内容涵盖三大模块：一是细胞组装与定位策略，重点分析细胞质、周质空间、细胞表面三类空间定位方式的技术原理、研究突破与适用场景；二是分子改造与高通量筛选技术体系，总结了从随机突变到计算驱动的多层次突变文库构建方法，以及无细胞提取物筛选、全细胞-光谱联用筛选等技术革新；三是场景化应用进展，详细阐述了其在肿瘤靶向治疗与高值化学品生物合成两大领域的代表性研究。最后，分析了该领域在金属辅因子稳定性、蛋白表达调控及催化性能优化等方面面临的挑战，并对人工智能与合成生物学深度融合驱动的未来发展方向进行了展望。

Abstract

Artificial metalloenzymes (ArMs) are biohybrid catalysts that integrate non-natural metal catalytic centers into protein scaffolds. By combining the broad reaction diversity of metal catalysts with the precise recognition capability of biological macromolecules

ArMs provide a critical tool for expanding the catalytic boundaries of natural enzymes. In vitro reconstituted ArMs have demonstrated unique advantages in a range of asymmetric transformations

including transfer hydrogenation

cyclopropanation

Michael addition

and C–H bond functionalization. However

their practical application remains constrained by multiple limitations

including high protein purification costs

insufficient stability

challenges in cofactor regeneration

and limited compatibility with complex reaction environments. Constructing ArMs within living cells or cell-derived systems enhances catalyst stability and production efficiency by leveraging the host cells′ intrinsic metabolic networks

protective mechanisms

and compartmentalized structures. Furthermore

whole-cell systems support autonomous cofactor regeneration

multi-step cascade reactions

and high-throughput directed evolution screening

demonstrating remarkable potential for industrial applications. In recent years

whole-cell ArM systems have achieved non-natural catalytic reactions including olefin metathesis and C–H bond activation

thereby expanding the inherent reaction scope of natural enzymes. Nevertheless

their development still faces core challenges in catalytic efficiency optimization

metal cofactor delivery

and large-scale preparation. This review systematically summarizes engineering strategies and application progress for ArMs in whole-cell systems

and is organized into three core modules. First

intracellular assembly and localization strategies are discussed

covering the fundamental principles and breakthroughs in cytoplasmic assembly

periplasmic localization

and cell-surface display. Second

the technological framework of protein engineering and high-throughput screening is reviewed

including multi-level mutant library construction and various innovative screening approaches. Third

scenario-based applications are examined

with emphasis on tumor-targeted therapy and high-value chemical biosynthesis. Finally

future directions are discussed

highlighting the deep integration of artificial intelligence and synthetic biology as a key driver of future technological advancement. The insights presented in this review are expected to provide theoretical support and decision-making references for the development of efficient and stable bio–non-biological hybrid catalytic systems.

关键词

Keywords

references

VALDEZ C E , SMITH Q A , NECHAY M R , et al . Mysteries of metals in metalloenzymes [J ] . Accounts of Chemical Research , 2014 , 47 ( 10 ): 3110 - 3117 .

SCHMID A , DORDICK J S , HAUER B , et al . Industrial biocatalysis today and tomorrow [J ] . Nature , 2001 , 409 ( 6817 ): 258 - 268 .

DAVIS H J , WARD T R . Artificial Metalloenzymes: Challenges and Opportunities [J ] . ACS Central Science , 2019 , 5 ( 7 ): 1120 - 1136 .

AKABORI S , SAKURAI S , IZUMI Y , et al . An Asymmetric Catalyst [J ] . Nature , 1956 , 178 ( 4528 ).

WILSON M E , WHITESIDES G M . Conversion of a protein to a homogeneous asymmetric hydrogenation catalyst by site-specific modification with a diphosphinerhodium (I) moiety [J ] . Journal of the American Chemical Society , 1978 , 100 ( 1 ): 306 - 307 .

YEUNG N , LIN Y-W , GAO Y-G , et al . Rational design of a structural and functional nitric oxide reductase [J ] . Nature , 2009 , 462 ( 7276 ): 1079 - 1082 .

MIRTS E N , PETRIK I D , HOSSEINZADEH P , et al . A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme [J ] . Science , 2018 , 361 ( 6407 ): 1098 - 1101 .

SONG W J , TEZCAN F A . A designed supramolecular protein assembly with in vivo enzymatic activity [J ] . Science , 2014 , 346 ( 6216 ): 1525 - 1528 .

KALVET I , ORTMAYER M , ZHAO J , et al . Design of heme enzymes with a tunable substrate binding pocket adjacent to an open metal coordination site [J ] . Journal of the American Chemical Society , 2023 , 145 ( 26 ): 14307 - 14315 .

BASLER S , STUDER S , ZOU Y , et al . Efficient Lewis acid catalysis of an abiological reaction in a de novo protein scaffold [J ] . Nature Chemistry , 2021 , 13 ( 3 ): 231 - 235 .

HUANG J , LIU Z , BLOOMER B J , et al . Unnatural biosynthesis by an engineered microorganism with heterologously expressed natural enzymes and an artificial metalloenzyme [J ] . Nature Chemistry , 2021 , 13 ( 12 ): 1186 - 1191 .

WU T , CHEN X , FEI Y , et al . Artificial metalloenzyme assembly in cellular compartments for enhanced catalysis [J ] . Nature Chemical Biology , 2025 , 21 ( 5 ): 779 - 789 .

MORRIS E , LOZHKIN B , UHRHAN J , et al . Design, Optimization and Characterization of a de novo Gold Hydroaminase [J ] . ACS Catalysis , 2026 , 16 ( 7 ): 6387 - 6395 .

WITTWER M , MARKEL U , SCHIFFELS J , et al . Engineering and emerging applications of artificial metalloenzymes with whole cells [J ] . Nature Catalysis , 2021 , 4 ( 10 ): 814 - 827 .

YAO Y , SU W , WU T , et al . Deploying Artificial Metalloenzymes in Complex Environments: Strategies and Applications [J ] . ChemBioChem , 2026 , 27 ( 13 ): e70446 .

JESCHEK M , REUTER R , HEINISCH T , et al . Directed evolution of artificial metalloenzymes for in vivo metathesis [J ] . Nature , 2016 , 537 ( 7622 ): 661 - 665 .

LIU Z , 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 [J ] . Journal of the American Chemical Society , 2022 , 144 ( 2 ): 883 - 890 .

ALONSO-COTCHICO L , RODRÍGUEZ-GUERRA J , LLEDOS A , et al . Molecular modeling for artificial metalloenzyme design and optimization [J ] . Accounts of Chemical Research , 2020 , 53 ( 4 ): 896 - 905 .

MARKEL U , SAUER D F , SCHIFFELS J , et al . Towards the evolution of artificial metalloenzymes—A protein engineer′s perspective [J ] . Angewandte Chemie International Edition , 2019 , 58 ( 14 ): 4454 - 4464 .

LOVELOCK S L , CRAWSHAW R , BASLER S , et al . The road to fully programmable protein catalysis [J ] . Nature , 2022 , 606 ( 7912 ): 49 - 58 .

LI Z Q , DENG Y T , YANG G Y . Growth-coupled high throughput selection for directed enzyme evolution [J ] . Biotechnology Advances , 2023 , 68 : 108238 .

KEASLING J D . Synthetic biology and the development of tools for metabolic engineering [J ] . Metabolic Engineering , 2012 , 14 ( 3 ): 189 - 195 .

SCHWIZER F , OKAMOTO Y , HEINISCH T , et al . Artificial Metalloenzymes: Reaction Scope and Optimization Strategies [J ] . Chemical Reviews , 2018 , 118 ( 1 ): 142 - 231 .

VORNHOLT T , LEISS-MAIER F , JEONG W J , et al . Artificial metalloenzymes [J ] . Nature Reviews Methods Primers , 2024 , 4 ( 1 ): 78 .

NATOLI S N , HARTWIG J F . Noble-Metal Substitution in Hemoproteins: An Emerging Strategy for Abiological Catalysis [J ] . Accounts of Chemical Research , 2019 , 52 ( 2 ): 326 - 335 .

HIROTA S , LIN Y-W . Design of artificial metalloproteins/metalloenzymes by tuning noncovalent interactions [J ] . Journal of Biological Inorganic Chemistry , 2018 , 23 ( 1 ): 7 - 25 .

DÜRRENBERGER M , WARD T R . Recent achievements in the design and engineering of artificial metalloenzymes [J ] . Current Opinion in Chemical Biology , 2014 , 19 : 99 - 106 .

ROSATI F , ROELFES G . Artificial Metalloenzymes [J ] . ChemCatChem , 2010 , 2 ( 8 ): 916 - 927 .

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

LIU X Y , HUANG C Q , JIN X R , et al . Research progress of artificial metalloenzymes [J ] . China Biotechnology , 2023 , 43 : 72 - 84 .

WOLFE J A , HORNE W S . Application of artificial backbone connectivity in the development of metalloenzyme mimics [J ] . Current Opinion in Chemical Biology , 2024 , 81 : 102509 .

LIN Y-W . Rational design of metalloenzymes: From single to multiple active sites [J ] . Coordination Chemistry Reviews , 2017 , 336 : 1 - 27 .

ILIE A , REETZ M T . Directed Evolution of Artificial Metalloenzymes [J ] . Israel Journal of Chemistry , 2015 , 55 ( 1 ): 51 - 60 .

MIRTS E N , BHAGI-DAMODARAN A , LU Y . Understanding and Modulating Metalloenzymes with Unnatural Amino Acids, Non-Native Metal Ions, and Non-Native Metallocofactors [J ] . Accounts of Chemical Research , 2019 , 52 ( 4 ): 935 - 944 .

ZOU Z , HIGGINSON B , WARD T R . Creation and optimization of artificial metalloenzymes: Harnessing the power of directed evolution and beyond [J ] . Chem , 2024 , 10 ( 8 ): 2373 - 2389 .

REETZ M T . Directed Evolution of Artificial Metalloenzymes: A Universal Means to Tune the Selectivity of Transition Metal Catalysts? [J ] . Accounts of Chemical Research , 2019 , 52 ( 2 ): 336 - 344 .

MORITA I , WARD T R . Recent advances in the design and optimization of artificial metalloenzymes [J ] . Current Opinion in Chemical Biology , 2024 , 81 : 102508 .

LEWIS J C . Artificial Metalloenzymes and Metallopeptide Catalysts for Organic Synthesis [J ] . ACS Catalysis , 2013 , 3 ( 12 ): 2954 - 2975 .

JESCHEK M , PANKE S , WARD T R . Artificial Metalloenzymes on the Verge of New-to-Nature Metabolism [J ] . Trends in Biotechnology , 2018 , 36 ( 1 ): 60 - 72 .

YANG X , GERROLL B H R , JIANG Y , et al . Controlling Non-Native Cobalamin Reactivity and Catalysis in the Transcription Factor CarH [J ] . ACS Catalysis , 2022 , 12 ( 2 ): 935 - 942 .

LEVESON-GOWER R B , MAYER C , ROELFES G . The importance of catalytic promiscuity for enzyme design and evolution [J ] . Nature Reviews Chemistry , 2019 , 3 ( 12 ): 687 - 705 .

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 [J ] . Journal of the American Chemical Society , 2023 , 145 ( 15 ): 8285 - 8290 .

WILSON Y M , DÜRRENBERGER M , NOGUEIRA E S , et al . Neutralizing the Detrimental Effect of Glutathione on Precious Metal Catalysts [J ] . Journal of the American Chemical Society , 2014 , 136 ( 25 ): 8928 - 8932 .

SZPONARSKI M , SCHWIZER F , WARD T R , et al . On-cell catalysis by surface engineering of live cells with an artificial metalloenzyme [J ] . Communications Chemistry , 2018 , 1 ( 1 ): 84 .

GHATTAS W , DUBOSCLARD V , WICK A , et al . Receptor-Based Artificial Metalloenzymes on Living Human Cells [J ] . Journal of the American Chemical Society , 2018 , 140 ( 28 ): 8756 - 8762 .

WINTER M B , MCLAURIN E J , REECE S Y , et al . Ru-porphyrin protein scaffolds for sensing O 2 [J ] . Journal of the American Chemical Society , 2010 , 132 ( 16 ): 5582 - 5583 .

NAUGHTON K J , TREVIÑO R E , MOORE P J , et al . In Vivo Assembly of a Genetically Encoded Artificial Metalloenzyme for Hydrogen Production [J ] . ACS Synthetic Biology , 2021 , 10 ( 8 ): 2116 - 2120 .

CHORDIA S , NARASIMHAN S , LUCINI PAIONI A , et al . In vivo assembly of artificial metalloenzymes and application in whole‐cell biocatalysis [J ] . Angewandte Chemie International Edition , 2021 , 60 ( 11 ): 5913 - 5920 .

BROUWER B , DELLA-FELICE F , ILLIES J H , et al . Noncanonical Amino Acids: Bringing New-to-Nature Functionalities to Biocatalysis [J ] . Chemical reviews , 2024 , 124 ( 19 ): 10877 - 10923 .

DRIENOVSKÁ I , RIOZ-MARTÍNEZ A , DRAKSHARAPU A , et al . Novel artificial metalloenzymes by in vivo incorporation of metal-binding unnatural amino acids [J ] . Chemical Science , 2015 , 6 ( 1 ): 770 - 776 .

DRIENOVSKÁ I , SCHEELE R A , GUTIÉRREZ DE SOUZA C , et al . A Hydroxyquinoline-Based Unnatural Amino Acid for the Design of Novel Artificial Metalloenzymes [J ] . ChemBioChem , 2020 , 21 ( 21 ): 3077 - 3081 .

DUAN H-Z , HU C , LI Y-L , et al . Genetically Encoded Phosphine Ligand for Metalloprotein Design [J ] . Journal of the American Chemical Society , 2022 , 144 ( 50 ): 22831 - 22837 .

VEEN M J , AALBERS F S , ROZEBOOM H J , et al . Artificial Gold Enzymes Using a Genetically Encoded Thiophenol-Based Noble-Metal-Binding Ligand [J ] . Angewandte Chemie International Edition , 2025 , 64 ( 12 ): e202421912 .

OFORI ATTA L , ZHOU Z , ROELFES G . In Vivo Biocatalytic Cascades Featuring an Artificial‐Enzyme‐Catalysed New‐to‐Nature Reaction [J ] . Angewandte Chemie , 2023 , 135 ( 1 ): e202214191 .

ZHAO J , REBELEIN J G , MALLIN H , et al . Genetic engineering of an artificial metalloenzyme for transfer hydrogenation of a self-immolative substrate in Escherichia coli 's periplasm [J ] . Journal of the American Chemical Society , 2018 , 140 ( 41 ): 13171 - 13175 .

VORNHOLT T , CHRISTOFFEL F , PELLIZZONI M M , et al . Systematic engineering of artificial metalloenzymes for new-to-nature reactions [J ] . Science Advances , 2021 , 7 ( 4 ): eabe4208 .

REBELEIN J G , COTELLE Y , GARABEDIAN B , et al . Chemical Optimization of Whole-Cell Transfer Hydrogenation Using Carbonic Anhydrase as Host Protein [J ] . ACS Catalysis , 2019 , 9 ( 5 ): 4173 - 4178 .

HEINISCH T , SCHWIZER F , GARABEDIAN B , et al . E. coli surface display of streptavidin for directed evolution of an allylic deallylase [J ] . Chemical science , 2018 , 9 ( 24 ): 5383 - 5388 .

XU Y , LI F , XIE H , et al . Directed evolution of Escherichia coli surface-displayed Vitreoscilla hemoglobin as an artificial metalloenzyme for the synthesis of 5-imino-1, 2, 4-thiadiazoles [J ] . Chemical Science , 2024 , 15 ( 20 ): 7742 - 7748 .

STEIN A , CHEN D , IGARETA N V , et al . A Dual Anchoring Strategy for the Directed Evolution of Improved Artificial Transfer Hydrogenases Based on Carbonic Anhydrase [J ] . ACS Central Science , 2021 , 7 ( 11 ): 1874 - 1884 .

BECKER S , THEILE S , HEPPELER N , et al . A generic system for the Escherichia coli cell-surface display of lipolytic enzymes [J ] . FEBS letters , 2005 , 579 ( 5 ): 1177 - 1182 .

GRIMM A R , SAUER D F , POLEN T , et al . A whole cell E. coli display platform for artificial metalloenzymes: poly (phenylacetylene) production with a rhodium–nitrobindin metalloprotein [J ] . ACS catalysis , 2018 , 8 ( 3 ): 2611 - 2614 .

ZOU Z , WU S , GERNGROSS D , et al . Combining an artificial metathase with a fatty acid decarboxylase in a whole cell for cycloalkene synthesis [J ] . Nature Synthesis , 2024 , 3 ( 9 ): 1113 - 1123 .

JEONG W J , SONG W J . Design and directed evolution of noncanonical β-stereoselective metalloglycosidases [J ] . Nature Communications , 2022 , 13 ( 1 ): 6844 .

LIN B X , TAO Y . Whole-cell biocatalysts by design [J ] . Microbial Cell Factories , 2017 , 16 ( 1 ): 106 .

GARGIULO S , SOUMILLION P . Directed evolution for enzyme development in biocatalysis [J ] . Current Opinion in Chemical Biology , 2021 , 61 : 107 - 113 .

PRITCHARD L , CORNE D , KELL D , et al . A general model of error-prone PCR [J ] . Journal of theoretical biology , 2005 , 234 ( 4 ): 497 - 509 .

STEMMER W P . Rapid evolution of a protein in vitro by DNA shuffling [J ] . Nature , 1994 , 370 ( 6488 ): 389 - 391 .

YANG H , SWARTZ A M , PARK H J , et al . Evolving artificial metalloenzymes via random mutagenesis [J ] . Nature Chemistry , 2018 , 10 ( 3 ): 318 - 324 .

QU G , LI A , ACEVEDO-ROCHA C G , et al . The Crucial Role of Methodology Development in Directed Evolution of Selective Enzymes [J ] . Angewandte Chemie International Edition , 2020 , 59 ( 32 ): 13204 - 13231 .

LEMAN J K , WEITZNER B D , LEWIS S M , et al . Macromolecular modeling and design in Rosetta: recent methods and frameworks [J ] . Nature Methods , 2020 , 17 ( 7 ): 665 - 680 .

REETZ M T , BOCOLA M , CARBALLEIRA J D , et al . Expanding the range of substrate acceptance of enzymes: Combinatorial active-site saturation test [J ] . Angew Chem , Int Ed, 2005 , 44 ( 27 ): 4192 - 4196 .

REETZ M T , PRASAD S , CARBALLEIRA J D , et al . Iterative Saturation Mutagenesis Accelerates Laboratory Evolution of Enzyme Stereoselectivity: Rigorous Comparison with Traditional Methods [J ] . J Am Chem Soc , 2010 , 132 ( 26 ): 9144 - 9152 .

MUKHERJEE P , SAIRAMAN A , DEKA H J , et al . Enantiodivergent synthesis of isoindolones catalysed by a Rh(III)-based artificial metalloenzyme [J ] . Nature Synthesis , 2024 , 3 ( 7 ): 835 - 845 .

MALLIN H , HESTERICOVÁ M , REUTER R , et al . Library design and screening protocol for artificial metalloenzymes based on the biotin-streptavidin technology [J ] . Nature Protocols , 2016 , 11 ( 5 ): 835 - 852 .

HESTERICOVÁ M , HEINISCH T , ALONSO-COTCHICO L , et al . Directed Evolution of an Artificial Imine Reductase [J ] . Angewandte Chemie International Edition , 2018 , 57 ( 7 ): 1863 - 1868 .

BAIYOUMY A , VALLAPURACKAL J , SCHWIZER F , et al . Directed evolution of a surface-displayed artificial allylic deallylase relying on a GFP reporter protein [J ] . ACS catalysis , 2021 , 11 ( 17 ): 10705 - 10712 .

VALLAPURACKAL J , STUCKI A , LIANG A D , et al . Ultrahigh‐throughput screening of an artificial metalloenzyme using double emulsions [J ] . Angewandte Chemie International Edition , 2022 , 61 ( 48 ): e202207328 .

CHRISTOFFEL F , IGARETA N V , PELLIZZONI M M , et al . Design and evolution of chimeric streptavidin for protein-enabled dual gold catalysis [J ] . Nature Catalysis , 2021 , 4 ( 8 ): 643 - 653 .

GU Y , BLOOMER B J , LIU Z , et al . Directed evolution of artificial metalloenzymes in whole cells [J ] . Angewandte Chemie , 2022 , 134 ( 5 ): e202110519 .

SRIVASTAVA P , YANG H , ELLIS-GUARDIOLA K , et al . Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation [J ] . Nature Communications , 2015 , 6 ( 1 ): 7789 .

EDA S , NASIBULLIN I , VONG K , et al . Biocompatibility and therapeutic potential of glycosylated albumin artificial metalloenzymes [J ] . Nature Catalysis , 2019 , 2 ( 9 ): 780 - 792 .

IMAI K , MUGURUMA K , NAKAMURA A , et al . In vivo synthetic anticancer approach by resourcing mouse blood albumin as a biocompatible artificial metalloenzyme [J ] . Angewandte Chemie International Edition , 2024 , 63 ( 43 ): e202411225 .

GAO Z , QIN K , HE W , et al . Chemocatalytic Cell Tagging Platform for Recording Cell‐Cell Interactions via Engineered Palladium‐Based Artificial Metalloenzymes [J ] . Angewandte Chemie International Edition , 2025 , 64 ( 20 ): e202424738 .

WU T , FEI Y , DENG Y , et al . Creation of Artificial Subcellular Organelles Using Compartmentalized Escherichia coli Bodies for Artificial Metalloenzyme-Mediated Abiotic Catalysis in Eukaryotic Cells [J ] . Journal of the American Chemical Society , 2025 , 147 ( 18 ): 15229 - 15241 .

LI Y , HAO Y , LI X , et al . Engineering artificial metalloenzymes for targeted biocatalysis in living organism [J ] . Chemical Engineering Journal , 2025 , 520 : 166074 .

RUMO C , STEIN A , KLEHR J , et al . An artificial metalloenzyme based on a copper heteroscorpionate enables sp 3 C–H functionalization via intramolecular carbene insertion [J ] . Journal of the American Chemical Society , 2022 , 144 ( 26 ): 11676 - 11684 .

ZHOU Z , ROELFES G . Synergistic catalysis in an artificial enzyme by simultaneous action of two abiological catalytic sites [J ] . Nature Catalysis , 2020 , 3 ( 3 ): 289 - 294 .

TANG Y , XU Y , ZHANG X , et al . Enzyme-Controlled Bidirectional Enantioselectivity in Asymmetric Decarboxylative Mannich Reaction for Synthesizing β-Sulfonamide Ketones [J ] . ACS Catalysis , 2025 , 15 ( 6 ): 4784 - 4797 .

ZHANG J , ZHANG Q , GE R , et al . Enantiodivergent Radical Alkylation by Synergistic Lewis‐Acid‐Enzyme and Photoredox Catalysis [J ] . Angewandte Chemie , 2025 , 64 ( 25 ): e202500338 .

ZOU Z , KALVET I , LOZHKIN B , et al . De novo design and evolution of an artificial metathase for cytoplasmic olefin metathesis [J ] . Nature Catalysis , 2025 , 8 ( 11 ): 1208 - 1219 .

ZHANG G , ZHANG A , ZHANG L , et al . The Impact of Structure Refinement in the Construction of Whole-Cell Catalysts with Artificial Metalloenzymes Assembled in Artificial Sanctuaries [J ] . Biomacromolecules , 2025 , 26 ( 12 ): 8837 - 8847 .

YU W , JIN K , XU X , et al . Engineering microbial cell factories by multiplexed spatiotemporal control of cellular metabolism: Advances, challenges, and future perspectives [J ] . Biotechnology Advances , 2025 , 79 : 108497 .

LA GATTA S , PECORARO V L . Recent advances in de novo designed metallopeptides as tailored enzyme mimics [J ] . Current Opinion in Chemical Biology , 2025 , 86 : 102586 .

SANTI M , SANCINETO L , NASCIMENTO V , et al . Flow biocatalysis: A challenging alternative for the synthesis of APIs and natural compounds [J ] . International journal of molecular sciences , 2021 , 22 ( 3 ): 990 .

AU S K , BOMMARIUS B R , BOMMARIUS A S . Biphasic Reaction System Allows for Conversion of Hydrophobic Substrates by Amine Dehydrogenases [J ] . ACS Catalysis , 2014 , 4 ( 11 ): 4021 - 4026 .

ZHANG Y , ZHANG J , CAI S , et al . Molecular Engineering and Utilization of Cyclohexanone Monooxygenase in the Cascade Biocatalytic Synthesis of ε-Caprolactone [J ] . ACS Sustainable Chemistry & Engineering , 2025 , 13 ( 17 ): 6090 - 6101 .

MA W , YANG Y , ZHU J , et al . Biomimetic nanoerythrosome‐coated aptamer–DNA tetrahedron/maytansine conjugates: pH‐responsive and targeted cytotoxicity for HER2‐positive breast cancer [J ] . Advanced Materials , 2022 , 34 ( 46 ): 2109609 .

CHEN H , BAO Y , LI X , et al . Cell Surface Engineering by Phase‐Separated Coacervates for Antibody Display and Targeted Cancer Cell Therapy [J ] . Angewandte Chemie , 2024 , 136 ( 44 ): e202410566 .

LI Q-R , ZHANG X , ZHANG C , et al . Biomineralized Engineered Bacterial Outer Membrane Vesicles as cGAS-STING Nanoagonists Synergize with Lactate Metabolism Modulation to Potentiate Immunotherapy [J ] . Journal of the American Chemical Society , 2025 , 147 ( 28 ): 2 4555– 24572 .

QING S , LYU C , ZHU L , et al . Biomineralized Bacterial Outer Membrane Vesicles Potentiate Safe and Efficient Tumor Microenvironment Reprogramming for Anticancer Therapy [J ] . Advanced Materials , 2020 , 32 ( 47 ): 2002085 .

YANG Y , WANG Y , ZENG F , et al . Ultrasound-visible engineered bacteria for tumor chemo-immunotherapy [J ] . Cell Reports Medicine , 2024 , 5 ( 5 ): 101512 .

HUANG J , ZHANG L , ZHENG J , et al . Microbubbles-assisted ultrasonication to promote tumor accumulation of therapeutics and modulation of tumor microenvironment for enhanced cancer treatments [J ] . Biomaterials , 2023 , 299 : 122181 .

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Related Institution

Department of Bioengineering and Technology， College of Chemical Engineering/Institute of Advanced Carbon Conversion Technology， Huaqiao University

The Key Laboratory for Synthetic Biotechnology of Xiamen City，Department of Chemical Engineering and Bioengineering， College of Chemistry and Chemical Engineering， Xiamen University

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Department of Bioengineering， College of Chemistry and Chemical Engineering， the North University of China

College of Food Science and Nutritional Engineering， China Agricultural University

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