Pub Date : 2025-10-24DOI: 10.1038/s41929-025-01420-8
Y. Koga, I. Fukumoto, K. Masui, T. Tanaka, Y. Naganawa, M. Hayashi, T. Ohshima, R. Yazaki
Deuterium-labelled compounds play a crucial role in drug discovery as both diagnostic tools and deuterated pharmaceuticals. While hydrogen isotope exchange is well established for activated substrates, the catalytic deuteration of unactivated amides and esters remains underdeveloped, particularly under mild conditions suitable for sensitive pharmaceuticals and polymers. This limitation hampers the late-stage modification of pharmaceutical molecules and functional materials. Here we report a catalytic hydrogen isotope exchange method using cooperative catalysts—a silicon Lewis acid and a tertiary amine base—functioning as a frustrated Lewis pair. This approach enables highly selective deuteration under mild conditions. Our method achieves high deuterium incorporation in various functionalized pharmaceuticals and polyesters, including those typically unstable under basic conditions, demonstrating its broad applicability. Deuterated bioactive compounds are important as diagnostic tools and pharmaceuticals, but current methods of development are limited. Here the authors report how a silicon Lewis acid and a tertiary amine base act as a frustrated Lewis pair to catalyse the hydrogen exchange reaction for the deuteration of amides and esters.
{"title":"Silicon frustrated Lewis pairs catalyse α-deuteration of amides and esters","authors":"Y. Koga, I. Fukumoto, K. Masui, T. Tanaka, Y. Naganawa, M. Hayashi, T. Ohshima, R. Yazaki","doi":"10.1038/s41929-025-01420-8","DOIUrl":"10.1038/s41929-025-01420-8","url":null,"abstract":"Deuterium-labelled compounds play a crucial role in drug discovery as both diagnostic tools and deuterated pharmaceuticals. While hydrogen isotope exchange is well established for activated substrates, the catalytic deuteration of unactivated amides and esters remains underdeveloped, particularly under mild conditions suitable for sensitive pharmaceuticals and polymers. This limitation hampers the late-stage modification of pharmaceutical molecules and functional materials. Here we report a catalytic hydrogen isotope exchange method using cooperative catalysts—a silicon Lewis acid and a tertiary amine base—functioning as a frustrated Lewis pair. This approach enables highly selective deuteration under mild conditions. Our method achieves high deuterium incorporation in various functionalized pharmaceuticals and polyesters, including those typically unstable under basic conditions, demonstrating its broad applicability. Deuterated bioactive compounds are important as diagnostic tools and pharmaceuticals, but current methods of development are limited. Here the authors report how a silicon Lewis acid and a tertiary amine base act as a frustrated Lewis pair to catalyse the hydrogen exchange reaction for the deuteration of amides and esters.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"1062-1071"},"PeriodicalIF":44.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371980","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 : 2025-10-24DOI: 10.1038/s41929-025-01433-3
Xinjie Yang, Juan Guo, Junyi Qian, Jianjian Huang, Juan Shi, Miao Jiang, Junshuai Zhang, Tengfei Pang, Ningning Sun, Yu Fu, Weining Zhao, Guojiao Wu, Xi Chen, Yuzhou Wu, Fangrui Zhong
Enzyme compartmentalization is a ubiquitous biochemical mechanism that nature uses to perform simultaneous but chemically incompatible metabolic processes in physically separated environments. However, it is a substantial challenge in homogeneous catalysis to spatially confine specific reaction components to prevent undesired pathways. Here we exploit the concept of compartmentalized enantioselective energy transfer catalysis by integrating artificial triplet photoenzymes and tailored triplet quenchers. The confined protein cavity was genetically encoded with a photosensitizer for enantioselective [2 + 2] photocycloaddition of 1-naphthol derivatives, while the outer bulk solution was modified with strategically introduced quenchers to inhibit the racemic background reaction induced by direct excitation, a fundamental challenge in asymmetric photocatalysis. This study not only expands the repertoire of artificial photoenzymes but also introduces a distinctive biocatalytic approach for precisely controlling reaction processes with spatial resolution, a capability that is usually unattainable in traditional chemocatalysis. Artificial photobiocatalytic reactions are appealing but sometimes suffer from non-enzymatic side reactions. Now a photoenzyme for enantioselective [2 + 2] photocycloaddition of 2-naphthyl derivatives is reported and combined with designed quenchers that shut down the competing enzyme-free racemic reaction.
{"title":"Enantioselective energy transfer catalysis compartmentalized by triplet photoenzymes","authors":"Xinjie Yang, Juan Guo, Junyi Qian, Jianjian Huang, Juan Shi, Miao Jiang, Junshuai Zhang, Tengfei Pang, Ningning Sun, Yu Fu, Weining Zhao, Guojiao Wu, Xi Chen, Yuzhou Wu, Fangrui Zhong","doi":"10.1038/s41929-025-01433-3","DOIUrl":"10.1038/s41929-025-01433-3","url":null,"abstract":"Enzyme compartmentalization is a ubiquitous biochemical mechanism that nature uses to perform simultaneous but chemically incompatible metabolic processes in physically separated environments. However, it is a substantial challenge in homogeneous catalysis to spatially confine specific reaction components to prevent undesired pathways. Here we exploit the concept of compartmentalized enantioselective energy transfer catalysis by integrating artificial triplet photoenzymes and tailored triplet quenchers. The confined protein cavity was genetically encoded with a photosensitizer for enantioselective [2 + 2] photocycloaddition of 1-naphthol derivatives, while the outer bulk solution was modified with strategically introduced quenchers to inhibit the racemic background reaction induced by direct excitation, a fundamental challenge in asymmetric photocatalysis. This study not only expands the repertoire of artificial photoenzymes but also introduces a distinctive biocatalytic approach for precisely controlling reaction processes with spatial resolution, a capability that is usually unattainable in traditional chemocatalysis. Artificial photobiocatalytic reactions are appealing but sometimes suffer from non-enzymatic side reactions. Now a photoenzyme for enantioselective [2 + 2] photocycloaddition of 2-naphthyl derivatives is reported and combined with designed quenchers that shut down the competing enzyme-free racemic reaction.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 11","pages":"1178-1187"},"PeriodicalIF":44.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145382002","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 : 2025-10-24DOI: 10.1038/s41929-025-01409-3
Kai Liu, Omer Markovitch, Chris van Ewijk, Yari Katar Knelissen, Armin Kiani, Marcel Eleveld, Wouter H. Roos, Sijbren Otto
The onset of Darwinian evolution represents a key step in the transition of chemical systems into living ones. Furthermore, Darwinian evolution is a tremendously powerful engine of invention, but one that has remained underdeveloped in synthetic chemical systems. Here we show the emergence of Darwinian evolution in two systems of self-replicating molecules in which natural selection favours replicator mutants best capable of catalysing the production of the precursors required for their own replication. Selection occurs based on the ability of the mutants to activate a photocatalyst as a cofactor that produces singlet oxygen which, in turn, enhances the rate by which peptide-based dithiol building blocks are converted into disulfide-based replicator precursors. Selection is based on a functional trait (catalytic activity), opening up Darwinian evolution as a tool for catalyst development. This work functionally integrates self-replication with protometabolism and Darwinian evolution, marking a further advance in the de novo synthesis of life. Darwinian evolution has shaped life on our planet through natural selection. Here, the authors report on the combination of self-replication, mutation and protometabolism in an out-of-equilibrium abiotic chemical system that can lead to natural selection for protometabolic activity.
{"title":"Selection for photocatalytic function through Darwinian evolution of synthetic self-replicators","authors":"Kai Liu, Omer Markovitch, Chris van Ewijk, Yari Katar Knelissen, Armin Kiani, Marcel Eleveld, Wouter H. Roos, Sijbren Otto","doi":"10.1038/s41929-025-01409-3","DOIUrl":"10.1038/s41929-025-01409-3","url":null,"abstract":"The onset of Darwinian evolution represents a key step in the transition of chemical systems into living ones. Furthermore, Darwinian evolution is a tremendously powerful engine of invention, but one that has remained underdeveloped in synthetic chemical systems. Here we show the emergence of Darwinian evolution in two systems of self-replicating molecules in which natural selection favours replicator mutants best capable of catalysing the production of the precursors required for their own replication. Selection occurs based on the ability of the mutants to activate a photocatalyst as a cofactor that produces singlet oxygen which, in turn, enhances the rate by which peptide-based dithiol building blocks are converted into disulfide-based replicator precursors. Selection is based on a functional trait (catalytic activity), opening up Darwinian evolution as a tool for catalyst development. This work functionally integrates self-replication with protometabolism and Darwinian evolution, marking a further advance in the de novo synthesis of life. Darwinian evolution has shaped life on our planet through natural selection. Here, the authors report on the combination of self-replication, mutation and protometabolism in an out-of-equilibrium abiotic chemical system that can lead to natural selection for protometabolic activity.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"1000-1009"},"PeriodicalIF":44.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371983","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 : 2025-10-24DOI: 10.1038/s41929-025-01428-0
Sulei Hu, Wei-Xue Li
Achieving long-term catalyst stability remains a grand challenge in catalysis. A recent study combines neural-network potential-based molecular dynamics simulations with decision tree-based interpretable machine learning, unveiling crucial support properties that guide the rational design of sinter-resistant platinum catalysts.
{"title":"A data-driven leap towards stable catalysts","authors":"Sulei Hu, Wei-Xue Li","doi":"10.1038/s41929-025-01428-0","DOIUrl":"10.1038/s41929-025-01428-0","url":null,"abstract":"Achieving long-term catalyst stability remains a grand challenge in catalysis. A recent study combines neural-network potential-based molecular dynamics simulations with decision tree-based interpretable machine learning, unveiling crucial support properties that guide the rational design of sinter-resistant platinum catalysts.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"981-983"},"PeriodicalIF":44.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371938","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 : 2025-10-24DOI: 10.1038/s41929-025-01441-3
Davide Esposito
{"title":"Urea from the plasma fan","authors":"Davide Esposito","doi":"10.1038/s41929-025-01441-3","DOIUrl":"10.1038/s41929-025-01441-3","url":null,"abstract":"","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"977-977"},"PeriodicalIF":44.6,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371947","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 : 2025-10-23DOI: 10.1038/s41929-025-01427-1
Zhihao Cui, Kassidy D. Aztergo, Jiseon Hwang, Anne C. Co
CO adsorption free energy ( $$Delta {G}_{{rm{C}}{rm{O}}}^{{rm{a}}{rm{d}}{rm{s}}}$$ ) has been proposed as a key descriptor for CO2 electroreduction (CO2R), yet its role remains unverified due to the lack of experimental methods capable of probing $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ under reaction conditions. Here we present a kinetic model combined with a rotating ring-disk electrode voltammetry method to estimate $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ on the active sites of various CO-producing catalysts during CO2R. Our results reveal that CO adsorption is influenced by multiple factors including catalyst type, cation identity and concentration, applied potential and surface structure. Notably, the measured difference in $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ between Au and Cu at CO2R-to-CO active sites is small, suggesting that the $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ of CO-producing active sites alone cannot account for Cu’s unique ability to catalyse CO2 into multicarbon products at appreciable rates. This study highlights the complexity of evaluating CO adsorption under CO2R conditions and introduces a robust experimental framework for quantifying $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ on CO-producing catalysts. CO adsorption free energy has been suggested as a descriptor to explain and predict CO2 reduction activity across various electrocatalysts, but methods for determining it experimentally under operating conditions are lacking. Here a kinetic model is combined with rotating ring-disk voltammetry to estimate this parameter.
{"title":"Determining CO adsorption free energies on CO2 electroreduction active sites through kinetic analysis","authors":"Zhihao Cui, Kassidy D. Aztergo, Jiseon Hwang, Anne C. Co","doi":"10.1038/s41929-025-01427-1","DOIUrl":"10.1038/s41929-025-01427-1","url":null,"abstract":"CO adsorption free energy ( $$Delta {G}_{{rm{C}}{rm{O}}}^{{rm{a}}{rm{d}}{rm{s}}}$$ ) has been proposed as a key descriptor for CO2 electroreduction (CO2R), yet its role remains unverified due to the lack of experimental methods capable of probing $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ under reaction conditions. Here we present a kinetic model combined with a rotating ring-disk electrode voltammetry method to estimate $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ on the active sites of various CO-producing catalysts during CO2R. Our results reveal that CO adsorption is influenced by multiple factors including catalyst type, cation identity and concentration, applied potential and surface structure. Notably, the measured difference in $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ between Au and Cu at CO2R-to-CO active sites is small, suggesting that the $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ of CO-producing active sites alone cannot account for Cu’s unique ability to catalyse CO2 into multicarbon products at appreciable rates. This study highlights the complexity of evaluating CO adsorption under CO2R conditions and introduces a robust experimental framework for quantifying $$Delta {G}_{mathrm{CO}}^{mathrm{ads}}$$ on CO-producing catalysts. CO adsorption free energy has been suggested as a descriptor to explain and predict CO2 reduction activity across various electrocatalysts, but methods for determining it experimentally under operating conditions are lacking. Here a kinetic model is combined with rotating ring-disk voltammetry to estimate this parameter.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"1117-1127"},"PeriodicalIF":44.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371981","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 : 2025-10-23DOI: 10.1038/s41929-025-01421-7
Paula Sebastián-Pascual, Antonia Herzog, Yirui Zhang, Yang Shao-Horn, María Escudero-Escribano
Electrolyte effects play a fundamental role in electrocatalysis, influencing reaction kinetics, selectivity and catalyst stability by altering interfacial interactions and charge distribution. Here we report recent advances to rationalize non-covalent interactions between electrolyte and surface adsorbates in electrocatalysis. Three main schools of thought have rationalized the effect of electrolyte–adsorbates–surface interactions on the reaction kinetics, each based on different descriptors. The first suggests that non-covalent interactions with the electrolyte modify the binding energies of the adsorbed intermediates. The second highlights the role of charge and electric fields near the electric double layer, shaped by the potential of zero charge, in stabilizing the polar adsorbates and governing proton transfer. The third focuses on energy barriers arising from the restructuring of the water solvation spheres of both electrolyte and reactants. We critically examine the main arguments and limitations of each framework, with a focus on hydrogen evolution and carbon dioxide reduction, and outline experimental challenges and future directions for elucidating electrolyte effects in electrocatalysis. The structure and properties of the electric double layer that forms at the electrode–electrolyte interface is crucial in determining the performance of electrocatalytic reactions. This Perspective puts forward and discusses three major schools of thought on electrolyte effects and electrocatalyst design.
{"title":"Electrolyte effects in proton–electron transfer reactions and implications for renewable fuels and chemicals synthesis","authors":"Paula Sebastián-Pascual, Antonia Herzog, Yirui Zhang, Yang Shao-Horn, María Escudero-Escribano","doi":"10.1038/s41929-025-01421-7","DOIUrl":"10.1038/s41929-025-01421-7","url":null,"abstract":"Electrolyte effects play a fundamental role in electrocatalysis, influencing reaction kinetics, selectivity and catalyst stability by altering interfacial interactions and charge distribution. Here we report recent advances to rationalize non-covalent interactions between electrolyte and surface adsorbates in electrocatalysis. Three main schools of thought have rationalized the effect of electrolyte–adsorbates–surface interactions on the reaction kinetics, each based on different descriptors. The first suggests that non-covalent interactions with the electrolyte modify the binding energies of the adsorbed intermediates. The second highlights the role of charge and electric fields near the electric double layer, shaped by the potential of zero charge, in stabilizing the polar adsorbates and governing proton transfer. The third focuses on energy barriers arising from the restructuring of the water solvation spheres of both electrolyte and reactants. We critically examine the main arguments and limitations of each framework, with a focus on hydrogen evolution and carbon dioxide reduction, and outline experimental challenges and future directions for elucidating electrolyte effects in electrocatalysis. The structure and properties of the electric double layer that forms at the electrode–electrolyte interface is crucial in determining the performance of electrocatalytic reactions. This Perspective puts forward and discusses three major schools of thought on electrolyte effects and electrocatalyst design.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"986-999"},"PeriodicalIF":44.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371982","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 : 2025-10-23DOI: 10.1038/s41929-025-01425-3
Srividya Murali, Guo-Bin Hu, Dale F. Kreitler, Ana Arroyo Carriedo, Luke C. Lewis, Samuel Adu Fosu, Olivia G. Weaver, Ella M. Buzas, Kathryn M. Byerly, Yasuo Yoshikuni, Sean McSweeney, Hannah S. Shafaat, Justin A. North
Bacteria utilize methylthio-alkane reductase (MAR) to acquire sulfur from volatile organic sulfur compounds. Reductive cleavage of methylthio-ethanol and dimethylsulfide liberates methanethiol for methionine synthesis and concomitantly releases ethylene and methane, respectively. Here we show that the native MAR of Rhodospirillum rubrum is a two-component system composed of a MarH ATP-dependent reductase and a MarDK catalytic core, whose architecture parallels nitrogenase. MarS complexes with MarDK to downregulate MAR activity during cellular sulfate influx, based on chromatographic and activity analyses. MarDK possesses complex metallocofactors resembling, but not identical to, nitrogenase P- and iron-only M-clusters, designated as mar1 and mar2 clusters based on metal, spectroscopic and mutagenesis analyses. They exhibit electronic features similar to the iron-only nitrogenase under turnover and, remarkably, are matured by MarB or nitrogenase NifB, resulting in maturase-dependent activity profiles. Altogether, this suggests a broader scope of reactivity, mechanisms and regulation in microbial metabolism for the nitrogenase-like family of enzymes than previously considered. Insights into the mechanism of methylthio-alkane reductase (MAR)—a nitrogenase-like enzyme essential for growth under sulfate-limited conditions—have remained scarce. Now a cryo-EM structure of MAR from Rhodospirillum rubrum, along with spectroscopic investigations, reveals how it uses complex metallocofactors for catalysis.
细菌利用甲基硫烷还原酶（MAR）从挥发性有机硫化合物中获取硫。甲基硫乙醇和二甲基硫化物的还原裂解释放甲硫醇用于蛋氨酸合成，同时分别释放乙烯和甲烷。本研究表明红红螺旋藻的天然MAR是一个由MAR atp依赖性还原酶和markk催化核心组成的双组分体系，其结构与氮酶相似。基于色谱和活性分析，MarS复合物与markk在细胞硫酸盐流入过程中下调MAR活性。markk具有复杂的金属辅助因子，类似于氮化酶P-和铁- m -簇，但不完全相同，根据金属，光谱和诱变分析，被称为mar1和mar2簇。它们表现出与纯铁氮酶相似的电子特征，值得注意的是，它们被MarB或氮酶NifB成熟，从而产生依赖于成熟酶的活性谱。总之，这表明在微生物代谢中，类氮酶家族的反应性、机制和调控范围比以前认为的要广泛。甲基硫代烷烃还原酶（MAR）是一种在硫酸盐限制条件下生长所必需的类似于氮酶的酶，对其机制的了解仍然很少。现在，红红螺旋藻MAR的低温电镜结构，以及光谱研究，揭示了它是如何使用复杂的金属辅助因子进行催化的。
{"title":"Architecture, catalysis and regulation of methylthio-alkane reductase for bacterial sulfur acquisition from volatile organic compounds","authors":"Srividya Murali, Guo-Bin Hu, Dale F. Kreitler, Ana Arroyo Carriedo, Luke C. Lewis, Samuel Adu Fosu, Olivia G. Weaver, Ella M. Buzas, Kathryn M. Byerly, Yasuo Yoshikuni, Sean McSweeney, Hannah S. Shafaat, Justin A. North","doi":"10.1038/s41929-025-01425-3","DOIUrl":"10.1038/s41929-025-01425-3","url":null,"abstract":"Bacteria utilize methylthio-alkane reductase (MAR) to acquire sulfur from volatile organic sulfur compounds. Reductive cleavage of methylthio-ethanol and dimethylsulfide liberates methanethiol for methionine synthesis and concomitantly releases ethylene and methane, respectively. Here we show that the native MAR of Rhodospirillum rubrum is a two-component system composed of a MarH ATP-dependent reductase and a MarDK catalytic core, whose architecture parallels nitrogenase. MarS complexes with MarDK to downregulate MAR activity during cellular sulfate influx, based on chromatographic and activity analyses. MarDK possesses complex metallocofactors resembling, but not identical to, nitrogenase P- and iron-only M-clusters, designated as mar1 and mar2 clusters based on metal, spectroscopic and mutagenesis analyses. They exhibit electronic features similar to the iron-only nitrogenase under turnover and, remarkably, are matured by MarB or nitrogenase NifB, resulting in maturase-dependent activity profiles. Altogether, this suggests a broader scope of reactivity, mechanisms and regulation in microbial metabolism for the nitrogenase-like family of enzymes than previously considered. Insights into the mechanism of methylthio-alkane reductase (MAR)—a nitrogenase-like enzyme essential for growth under sulfate-limited conditions—have remained scarce. Now a cryo-EM structure of MAR from Rhodospirillum rubrum, along with spectroscopic investigations, reveals how it uses complex metallocofactors for catalysis.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"1072-1085"},"PeriodicalIF":44.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41929-025-01425-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-23DOI: 10.1038/s41929-025-01426-2
Ana Lago-Maciel, Jéssica C. Soares, Jan Zarzycki, Charles J. Buchanan, Tristan Reif-Trauttmansdorff, Frederik V. Schmidt, Stefano Lometto, Nicole Paczia, Jan M. Schuller, D. Flemming Hansen, Gabriella T. Heller, Simone Prinz, Georg K. A. Hochberg, Antonio J. Pierik, Johannes G. Rebelein
Methylthio-alkane reductases convert methylated sulfur compounds to methanethiol and small hydrocarbons, a process with important environmental and biotechnological implications. These enzymes are classified as nitrogenase-like enzymes, despite lacking the ability to convert dinitrogen to ammonia, raising fundamental questions about the factors controlling their activity and specificity. Here we present the molecular structure of the methylthio-alkane reductase, which reveals large metalloclusters, including the P-cluster and the [Fe8S9C]-cluster, previously found only in nitrogenases. Our findings suggest that distinct metallocluster coordination, surroundings and substrate channels determine the activity of these related metalloenzymes. This study provides new insights into nitrogen fixation, sulfur-compound reduction and hydrocarbon production. We also shed light on the evolutionary history of P-cluster and [Fe8S9C]-cluster-containing reductases emerging before nitrogenases. Methylthio-alkane reductases are recently discovered enzymes that can produce methanethiol and small hydrocarbons from methylated sulfur compounds. Now the cryo-EM structure of a methylthio-alkane reductase complex is solved, revealing large metalloclusters previously observed only within nitrogenases.
{"title":"Methylthio-alkane reductases use nitrogenase metalloclusters for carbon–sulfur bond cleavage","authors":"Ana Lago-Maciel, Jéssica C. Soares, Jan Zarzycki, Charles J. Buchanan, Tristan Reif-Trauttmansdorff, Frederik V. Schmidt, Stefano Lometto, Nicole Paczia, Jan M. Schuller, D. Flemming Hansen, Gabriella T. Heller, Simone Prinz, Georg K. A. Hochberg, Antonio J. Pierik, Johannes G. Rebelein","doi":"10.1038/s41929-025-01426-2","DOIUrl":"10.1038/s41929-025-01426-2","url":null,"abstract":"Methylthio-alkane reductases convert methylated sulfur compounds to methanethiol and small hydrocarbons, a process with important environmental and biotechnological implications. These enzymes are classified as nitrogenase-like enzymes, despite lacking the ability to convert dinitrogen to ammonia, raising fundamental questions about the factors controlling their activity and specificity. Here we present the molecular structure of the methylthio-alkane reductase, which reveals large metalloclusters, including the P-cluster and the [Fe8S9C]-cluster, previously found only in nitrogenases. Our findings suggest that distinct metallocluster coordination, surroundings and substrate channels determine the activity of these related metalloenzymes. This study provides new insights into nitrogen fixation, sulfur-compound reduction and hydrocarbon production. We also shed light on the evolutionary history of P-cluster and [Fe8S9C]-cluster-containing reductases emerging before nitrogenases. Methylthio-alkane reductases are recently discovered enzymes that can produce methanethiol and small hydrocarbons from methylated sulfur compounds. Now the cryo-EM structure of a methylthio-alkane reductase complex is solved, revealing large metalloclusters previously observed only within nitrogenases.","PeriodicalId":18845,"journal":{"name":"Nature Catalysis","volume":"8 10","pages":"1086-1099"},"PeriodicalIF":44.6,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41929-025-01426-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145371979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：