Pub Date : 2025-09-24DOI: 10.1038/s41929-025-01400-y
Peter Westh, Jeppe Kari
The 1913 study ‘Die Kinetik der Invertinwirkung’, by Michaelis and Menten, marked a pivotal advancement in enzymology by illustrating the application of mechanistic models and quantitative kinetics to biocatalysis. The foundational framework described back then continues to have a strong impact on enzymology, with profound influences that range from undergraduate education to structure–function studies and the format and content of contemporary kinetic databases.
1913年Michaelis和Menten的研究“Die Kinetik der Invertinwirkung”，通过说明机理模型和定量动力学在生物催化中的应用，标志着酶学的关键进步。当时描述的基本框架继续对酶学产生强烈的影响，从本科教育到结构-功能研究以及当代动力学数据库的格式和内容都产生了深远的影响。
{"title":"From descriptive to quantitative biocatalysis","authors":"Peter Westh, Jeppe Kari","doi":"10.1038/s41929-025-01400-y","DOIUrl":"10.1038/s41929-025-01400-y","url":null,"abstract":"The 1913 study ‘Die Kinetik der Invertinwirkung’, by Michaelis and Menten, marked a pivotal advancement in enzymology by illustrating the application of mechanistic models and quantitative kinetics to biocatalysis. The foundational framework described back then continues to have a strong impact on enzymology, with profound influences that range from undergraduate education to structure–function studies and the format and content of contemporary kinetic databases.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 9","pages":"859-860"},"PeriodicalIF":44.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1038/s41929-025-01413-7
A TIM-barrel metalloenzyme — Art22 — involved in the sugar-moiety modification of the antibiotic aurantinin B (ART B) has been discovered. This enzyme activates 4-keto ART B to ART B through rapid isomerization. Additionally, Art22 slowly converts ART B into inactive products through oxidative cleavage of the 3-keto hexopyranose.
{"title":"A TIM-barrel metalloenzyme with sugar-cleavage activity","authors":"","doi":"10.1038/s41929-025-01413-7","DOIUrl":"10.1038/s41929-025-01413-7","url":null,"abstract":"A TIM-barrel metalloenzyme — Art22 — involved in the sugar-moiety modification of the antibiotic aurantinin B (ART B) has been discovered. This enzyme activates 4-keto ART B to ART B through rapid isomerization. Additionally, Art22 slowly converts ART B into inactive products through oxidative cleavage of the 3-keto hexopyranose.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"984-985"},"PeriodicalIF":44.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-24DOI: 10.1038/s41929-025-01410-w
Jiri Damborsky, Petr Kouba, Josef Sivic, Michal Vasina, David Bednar, Stanislav Mazurenko
Quantum computing, by leveraging the unique principles of quantum mechanics, offers transformative potential for biocatalysis and related disciplines. Compared to classical algorithms, quantum algorithms deliver immense acceleration to quantum computers, making them suited for tackling computationally challenging problems such as simulating many-body biomolecular systems or enzyme-catalysed chemical reactions. However, current quantum hardware is constrained by noise, limited qubit coherence and high error rates, restricting its capacity to model complex biochemical phenomena. Here we explore the rapidly advancing landscape of quantum computing and its future applications in the discovery and rational engineering of biocatalysts. We identify key areas where quantum algorithms could surpass classical limitations, including the quantum chemistry-based design of biocatalysts with enhanced catalytic activity or selectivity, parallelized mining of novel enzymes, accurate ancestral sequence reconstruction, and combinatorial in silico protein evolution. Overcoming current hardware limitations could unlock transformative advances in both fundamental enzymology and industrial bioprocessing. Quantum computing is a promising technology to solve complex challenges that would take classical computers an impractical amount of time. This Perspective discusses the current state of quantum computing and possible applications in enzyme engineering and biocatalysis.
{"title":"Quantum computing for faster enzyme discovery and engineering","authors":"Jiri Damborsky, Petr Kouba, Josef Sivic, Michal Vasina, David Bednar, Stanislav Mazurenko","doi":"10.1038/s41929-025-01410-w","DOIUrl":"10.1038/s41929-025-01410-w","url":null,"abstract":"Quantum computing, by leveraging the unique principles of quantum mechanics, offers transformative potential for biocatalysis and related disciplines. Compared to classical algorithms, quantum algorithms deliver immense acceleration to quantum computers, making them suited for tackling computationally challenging problems such as simulating many-body biomolecular systems or enzyme-catalysed chemical reactions. However, current quantum hardware is constrained by noise, limited qubit coherence and high error rates, restricting its capacity to model complex biochemical phenomena. Here we explore the rapidly advancing landscape of quantum computing and its future applications in the discovery and rational engineering of biocatalysts. We identify key areas where quantum algorithms could surpass classical limitations, including the quantum chemistry-based design of biocatalysts with enhanced catalytic activity or selectivity, parallelized mining of novel enzymes, accurate ancestral sequence reconstruction, and combinatorial in silico protein evolution. Overcoming current hardware limitations could unlock transformative advances in both fundamental enzymology and industrial bioprocessing. Quantum computing is a promising technology to solve complex challenges that would take classical computers an impractical amount of time. This Perspective discusses the current state of quantum computing and possible applications in enzyme engineering and biocatalysis.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 9","pages":"872-880"},"PeriodicalIF":44.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-23DOI: 10.1038/s41929-025-01398-3
Changxi Yang, Chenyu Wu, Wenbo Xie, Daiqian Xie, P. Hu
Developing truly universal machine learning potentials for heterogeneous catalysis remains challenging. Here we introduce our element-based machine learning potential (EMLP), trained on a unique random exploration via imaginary chemicals optimization (REICO) sampling strategy. REICO samples diverse local atomic environments to build a representative dataset of atomic interactions, making the EMLP inherently general and reactive, capable of accurately predicting elementary reactions without explicit structural or reaction pathway inputs. We demonstrate the generality and reactivity of our approach by building a Ag-Pd-C-H-O EMLP targeting Pd–Ag catalysts interacting with C/H/O-containing species, achieving quantitative agreement with density functional theory even for complex scenarios such as surface reconstruction, coverage effects and solvent environments, cases for which existing foundation models typically fail. Our method paves the way to replace density functional theory calculations for large and intricate systems in heterogeneous catalysis, and offers a general framework that can readily be extended to other catalytic systems, and to broader fields such as materials science. It is challenging to design machine learning potentials for heterogeneous catalysis that are universal, reactive and have high accuracy. Now, an element-based machine learning potential relying on a random exploration via an imaginary chemicals optimization sampling strategy is put forward, and is successfully demonstrated for a range of applications.
{"title":"General reactive element-based machine learning potentials for heterogeneous catalysis","authors":"Changxi Yang, Chenyu Wu, Wenbo Xie, Daiqian Xie, P. Hu","doi":"10.1038/s41929-025-01398-3","DOIUrl":"10.1038/s41929-025-01398-3","url":null,"abstract":"Developing truly universal machine learning potentials for heterogeneous catalysis remains challenging. Here we introduce our element-based machine learning potential (EMLP), trained on a unique random exploration via imaginary chemicals optimization (REICO) sampling strategy. REICO samples diverse local atomic environments to build a representative dataset of atomic interactions, making the EMLP inherently general and reactive, capable of accurately predicting elementary reactions without explicit structural or reaction pathway inputs. We demonstrate the generality and reactivity of our approach by building a Ag-Pd-C-H-O EMLP targeting Pd–Ag catalysts interacting with C/H/O-containing species, achieving quantitative agreement with density functional theory even for complex scenarios such as surface reconstruction, coverage effects and solvent environments, cases for which existing foundation models typically fail. Our method paves the way to replace density functional theory calculations for large and intricate systems in heterogeneous catalysis, and offers a general framework that can readily be extended to other catalytic systems, and to broader fields such as materials science. It is challenging to design machine learning potentials for heterogeneous catalysis that are universal, reactive and have high accuracy. Now, an element-based machine learning potential relying on a random exploration via an imaginary chemicals optimization sampling strategy is put forward, and is successfully demonstrated for a range of applications.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 9","pages":"891-904"},"PeriodicalIF":44.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Achieving mono-selectivity in C–H activation reactions is a considerable challenge when multiple identical C–H bonds coexist. Despite recent rapid advances in site-selective and enantioselective C–H activation, a large number of C–H activation reactions still suffer from poor mono-selectivity. Here we report the use of commercial enzymes as ligands for palladium catalysts, enabling enhanced reactivity and exceptionally high mono-selectivity (up to 99%) in both ortho- and meta-C–H activation of arenes, which originally used bifunctional mono-N-protected amino acid ligands but with poor mono-selectivity. Notably, the Pd–enzyme complex was identified as the active catalyst species. Mechanistic investigations and structural analyses of the enzymes suggest that the enzyme primary structure, the sequence length and the percentage of amino acids with hydrophobic side chains are critical for achieving mono-selectivity. By leveraging these findings, we further developed a glycine-containing oligopeptide capable of achieving similarly high mono-selectivity. Molecular organometallic catalysts typically struggle to activate only one of two identical C–H bonds in arenes for mono-selective C–H activation. Now mono-selectivity has been achieved for Pd(II)-catalysed ortho- or meta-C–H activations using commercial proteins or designed peptides as ligands.
{"title":"Achieving mono-selective palladium(II)-catalysed C–H activation of arenes with protein ligands","authors":"Hua-Jin Xu, Zhoulong Fan, Bin-Bin Nian, Chen-Hao Gu, Shuo-Jie Shen, Wei Zhang, Yi Hu, Jin-Quan Yu","doi":"10.1038/s41929-025-01407-5","DOIUrl":"10.1038/s41929-025-01407-5","url":null,"abstract":"Achieving mono-selectivity in C–H activation reactions is a considerable challenge when multiple identical C–H bonds coexist. Despite recent rapid advances in site-selective and enantioselective C–H activation, a large number of C–H activation reactions still suffer from poor mono-selectivity. Here we report the use of commercial enzymes as ligands for palladium catalysts, enabling enhanced reactivity and exceptionally high mono-selectivity (up to 99%) in both ortho- and meta-C–H activation of arenes, which originally used bifunctional mono-N-protected amino acid ligands but with poor mono-selectivity. Notably, the Pd–enzyme complex was identified as the active catalyst species. Mechanistic investigations and structural analyses of the enzymes suggest that the enzyme primary structure, the sequence length and the percentage of amino acids with hydrophobic side chains are critical for achieving mono-selectivity. By leveraging these findings, we further developed a glycine-containing oligopeptide capable of achieving similarly high mono-selectivity. Molecular organometallic catalysts typically struggle to activate only one of two identical C–H bonds in arenes for mono-selective C–H activation. Now mono-selectivity has been achieved for Pd(II)-catalysed ortho- or meta-C–H activations using commercial proteins or designed peptides as ligands.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 9","pages":"948-956"},"PeriodicalIF":44.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1038/s41929-025-01399-2
Francesca Lorenzutti, Ranga Rohit Seemakurthi, Evan F. Johnson, Santiago Morandi, Pavle Nikačević, Núria López, Sophia Haussener
Electrochemical CO2 reduction is expected to become a key player in net-zero technologies, yet its industrial implementation is currently limited. Improvements based on fine-tuning microenvironments (that is, electrolyte environments around catalytic sites) have been scarce due to the interplay between electrode kinetics and transport. Here we couple atomistic insights with continuum transport via ab initio multiscale modelling, explicitly including electrolyte effects at all scales. The resulting model is validated on silver planar electrodes in several liquid electrolytes, and the current dependence with voltage aligns with experimental observations. We show that a balance between CO2 diffusion and cation accumulation needs to be achieved to obtain optimal rates. In ionomers, this limitation can be overcome since organic cation-based microenvironments are present at a fixed concentration, but water management becomes critical. Our approach paves the way towards rational microenvironment design in electrochemical CO2 conversion. Optimizing devices for electrochemical CO2 reduction requires a comprehensive and quantitative understanding of the microenvironments where the reactions occur. Now, a multiscale modelling approach that explicitly accounts for electrolyte effects at all scales is developed and showcased for the electroreduction of CO2 on silver.
{"title":"Microenvironment effects in electrochemical CO2 reduction from first-principles multiscale modelling","authors":"Francesca Lorenzutti, Ranga Rohit Seemakurthi, Evan F. Johnson, Santiago Morandi, Pavle Nikačević, Núria López, Sophia Haussener","doi":"10.1038/s41929-025-01399-2","DOIUrl":"10.1038/s41929-025-01399-2","url":null,"abstract":"Electrochemical CO2 reduction is expected to become a key player in net-zero technologies, yet its industrial implementation is currently limited. Improvements based on fine-tuning microenvironments (that is, electrolyte environments around catalytic sites) have been scarce due to the interplay between electrode kinetics and transport. Here we couple atomistic insights with continuum transport via ab initio multiscale modelling, explicitly including electrolyte effects at all scales. The resulting model is validated on silver planar electrodes in several liquid electrolytes, and the current dependence with voltage aligns with experimental observations. We show that a balance between CO2 diffusion and cation accumulation needs to be achieved to obtain optimal rates. In ionomers, this limitation can be overcome since organic cation-based microenvironments are present at a fixed concentration, but water management becomes critical. Our approach paves the way towards rational microenvironment design in electrochemical CO2 conversion. Optimizing devices for electrochemical CO2 reduction requires a comprehensive and quantitative understanding of the microenvironments where the reactions occur. Now, a multiscale modelling approach that explicitly accounts for electrolyte effects at all scales is developed and showcased for the electroreduction of CO2 on silver.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 9","pages":"905-918"},"PeriodicalIF":44.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-08DOI: 10.1038/s41929-025-01408-4
Ning Li, Xuzhen Ye, Yong Liu, Jin Song
Carboxylic ester motifs are prevalent in biological, chemical and materials sciences, and the asymmetric α-functionalization of simple esters plays a crucial role in the field of organic synthesis. Here we present a versatile electricity-driven asymmetric Lewis base catalysis strategy for the oxidative radical cross-coupling of simple esters with silyl enol ethers. This approach integrates the electrochemical anodic oxidation process with chiral isothiourea catalysis, enabling a polarity inversion at the nucleophilic carbon of the enolate to trigger the formation of a chiral isothiourea-bound α-carbonyl radical species from a C1-ammonium enolate. The combination of asymmetric Lewis base catalysis and electrochemistry unlocks mild oxidative radical coupling reactions, achieving up to 98% enantiomeric excess and demonstrating broad substrate compatibility. This work underscores the synthetic potential of the approach and provides a platform for advancing asymmetric electrosynthesis. Strategies for asymmetric control in electrosynthesis involving radicals are sought after. Now asymmetric Lewis base catalysis is combined with electrochemistry, enabling the oxidative radical cross-coupling of esters with silyl enol ethers and affording γ-keto esters in high enantiomeric excess.
{"title":"Enantioselective radical α-enolation of esters via electrochemical chiral isothiourea catalysis","authors":"Ning Li, Xuzhen Ye, Yong Liu, Jin Song","doi":"10.1038/s41929-025-01408-4","DOIUrl":"10.1038/s41929-025-01408-4","url":null,"abstract":"Carboxylic ester motifs are prevalent in biological, chemical and materials sciences, and the asymmetric α-functionalization of simple esters plays a crucial role in the field of organic synthesis. Here we present a versatile electricity-driven asymmetric Lewis base catalysis strategy for the oxidative radical cross-coupling of simple esters with silyl enol ethers. This approach integrates the electrochemical anodic oxidation process with chiral isothiourea catalysis, enabling a polarity inversion at the nucleophilic carbon of the enolate to trigger the formation of a chiral isothiourea-bound α-carbonyl radical species from a C1-ammonium enolate. The combination of asymmetric Lewis base catalysis and electrochemistry unlocks mild oxidative radical coupling reactions, achieving up to 98% enantiomeric excess and demonstrating broad substrate compatibility. This work underscores the synthetic potential of the approach and provides a platform for advancing asymmetric electrosynthesis. Strategies for asymmetric control in electrosynthesis involving radicals are sought after. Now asymmetric Lewis base catalysis is combined with electrochemistry, enabling the oxidative radical cross-coupling of esters with silyl enol ethers and affording γ-keto esters in high enantiomeric excess.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 9","pages":"957-967"},"PeriodicalIF":44.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145009011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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