Pub Date : 2024-09-24DOI: 10.1038/s41557-024-01638-2
Quazi T. H. Shubhra
Liposomal systems frequently face challenges, such as low encapsulation efficiency and inadequate controlled release capabilities. Innovatively designed multi-compartment liposomes now overcome these limitations by facilitating precise control over cargo loading and release kinetics, and by serving as microreactors for biochemical synthesis.
{"title":"Multi-compartment liposomes forge new paths in drug delivery","authors":"Quazi T. H. Shubhra","doi":"10.1038/s41557-024-01638-2","DOIUrl":"10.1038/s41557-024-01638-2","url":null,"abstract":"Liposomal systems frequently face challenges, such as low encapsulation efficiency and inadequate controlled release capabilities. Innovatively designed multi-compartment liposomes now overcome these limitations by facilitating precise control over cargo loading and release kinetics, and by serving as microreactors for biochemical synthesis.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 10","pages":"1578-1579"},"PeriodicalIF":19.2,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142313987","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}
Halides of the family Li3MX6 (M = Y, In, Sc and so on, X = halogen) are emerging solid electrolyte materials for all-solid-state Li-ion batteries. They show greater chemical stability and wider electrochemical stability windows than existing sulfide solid electrolytes, but have lower room-temperature ionic conductivities. Here we report the discovery that the superionic transition in Li3YCl6 is triggered by the collective motion of anions, as evidenced by synchrotron X-ray and neutron scattering characterizations and ab initio molecular dynamics simulations. Based on this finding, we used a rational design strategy to lower the transition temperature and thus improve the room-temperature ionic conductivity of this family of compounds. We accordingly synthesized Li3YClxBr6−x and Li3GdCl3Br3 and achieved very high room-temperature conductivities of 6.1 and 11 mS cm−1 for Li3YCl4.5Br1.5 and Li3GdCl3Br3, respectively. These findings open new routes to the design of room-temperature superionic conductors for high-performance solid batteries. While solid-state lithium-ion batteries offer promising energy densities for safe energy storage, typical solid electrolytes show poor room-temperature ionic conduction. Now the origin of the superionic transition observed in Li3YCl6-type Li-ion conductors is revealed by in-depth crystal structure characterizations and improved ionic conductivities achieved by lowering the transition temperature.
Li3MX6 族卤化物（M = Y、In、Sc 等，X = 卤素）是新兴的全固态锂离子电池固态电解质材料。与现有的硫化物固态电解质相比，它们具有更高的化学稳定性和更宽的电化学稳定性窗口，但室温离子电导率较低。同步辐射 X 射线和中子散射表征以及 ab initio 分子动力学模拟证明，Li3YCl6 中的超离子转变是由阴离子的集体运动触发的。基于这一发现，我们采用了合理的设计策略来降低转变温度，从而提高该系列化合物的室温离子电导率。因此，我们合成了 Li3YClxBr6-x 和 Li3GdCl3Br3，并使 Li3YCl4.5Br1.5 和 Li3GdCl3Br3 的室温电导率分别达到了 6.1 和 11 mS cm-1。这些发现为设计用于高性能固体电池的室温超离子导体开辟了新的途径。
{"title":"Tuning collective anion motion enables superionic conductivity in solid-state halide electrolytes","authors":"Zhantao Liu, Po-Hsiu Chien, Shuo Wang, Shaowei Song, Mu Lu, Shuo Chen, Shuman Xia, Jue Liu, Yifei Mo, Hailong Chen","doi":"10.1038/s41557-024-01634-6","DOIUrl":"10.1038/s41557-024-01634-6","url":null,"abstract":"Halides of the family Li3MX6 (M = Y, In, Sc and so on, X = halogen) are emerging solid electrolyte materials for all-solid-state Li-ion batteries. They show greater chemical stability and wider electrochemical stability windows than existing sulfide solid electrolytes, but have lower room-temperature ionic conductivities. Here we report the discovery that the superionic transition in Li3YCl6 is triggered by the collective motion of anions, as evidenced by synchrotron X-ray and neutron scattering characterizations and ab initio molecular dynamics simulations. Based on this finding, we used a rational design strategy to lower the transition temperature and thus improve the room-temperature ionic conductivity of this family of compounds. We accordingly synthesized Li3YClxBr6−x and Li3GdCl3Br3 and achieved very high room-temperature conductivities of 6.1 and 11 mS cm−1 for Li3YCl4.5Br1.5 and Li3GdCl3Br3, respectively. These findings open new routes to the design of room-temperature superionic conductors for high-performance solid batteries. While solid-state lithium-ion batteries offer promising energy densities for safe energy storage, typical solid electrolytes show poor room-temperature ionic conduction. Now the origin of the superionic transition observed in Li3YCl6-type Li-ion conductors is revealed by in-depth crystal structure characterizations and improved ionic conductivities achieved by lowering the transition temperature.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 10","pages":"1584-1591"},"PeriodicalIF":19.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276710","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 : 2024-09-23DOI: 10.1038/s41557-024-01637-3
Cheng Ma
Although all-solid-state Li batteries offer a safe, energy-dense alternative to commercial Li-ion batteries, their development is impeded by the sluggish Li-ion transport within solid electrolytes. Now, anion configuration regulation has been shown to promote Li-ion migration, offering a new approach for designing highly Li-ion-conductive solid electrolytes.
{"title":"Regulated anion configuration enables ultrafast Li-ion transport","authors":"Cheng Ma","doi":"10.1038/s41557-024-01637-3","DOIUrl":"10.1038/s41557-024-01637-3","url":null,"abstract":"Although all-solid-state Li batteries offer a safe, energy-dense alternative to commercial Li-ion batteries, their development is impeded by the sluggish Li-ion transport within solid electrolytes. Now, anion configuration regulation has been shown to promote Li-ion migration, offering a new approach for designing highly Li-ion-conductive solid electrolytes.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 10","pages":"1569-1570"},"PeriodicalIF":19.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276715","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 : 2024-09-23DOI: 10.1038/s41557-024-01631-9
Latha Venkataraman, Jan van Ruitenbeek
{"title":"Questioning claims of monitoring the Michael addition reaction at the single-molecule level","authors":"Latha Venkataraman, Jan van Ruitenbeek","doi":"10.1038/s41557-024-01631-9","DOIUrl":"10.1038/s41557-024-01631-9","url":null,"abstract":"","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1767-1769"},"PeriodicalIF":19.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276707","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 : 2024-09-23DOI: 10.1038/s41557-024-01640-8
Zhu Cao, Chen Zhu
The translocation of alkenes and remote functional groups is an ingenious strategy to reorganize complex structures, yet it is rarely investigated, owing to the challenges in controlling multiple selectivities. Now, an efficient photo/cobalt dual-catalytic method has been developed to accomplish alkene difunctionalization.
{"title":"Intramolecular alkene and functional group translocation","authors":"Zhu Cao, Chen Zhu","doi":"10.1038/s41557-024-01640-8","DOIUrl":"10.1038/s41557-024-01640-8","url":null,"abstract":"The translocation of alkenes and remote functional groups is an ingenious strategy to reorganize complex structures, yet it is rarely investigated, owing to the challenges in controlling multiple selectivities. Now, an efficient photo/cobalt dual-catalytic method has been developed to accomplish alkene difunctionalization.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 10","pages":"1576-1577"},"PeriodicalIF":19.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276709","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 : 2024-09-23DOI: 10.1038/s41557-024-01632-8
Chen Yang, Kendall N. Houk, Yonatan Dubi, Xuefeng Guo
{"title":"Reply to: Questioning claims of monitoring the Michael addition reaction at the single-molecule level","authors":"Chen Yang, Kendall N. Houk, Yonatan Dubi, Xuefeng Guo","doi":"10.1038/s41557-024-01632-8","DOIUrl":"10.1038/s41557-024-01632-8","url":null,"abstract":"","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1770-1771"},"PeriodicalIF":19.2,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276712","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 : 2024-09-20DOI: 10.1038/s41557-024-01645-3
A method called flash-within-flash Joule heating (FWF) has been developed based on a dual reactor design, enabling the gram-scale synthesis of diverse inorganic materials within seconds. Comparison with commercially available materials suggests that FWF products can offer comparable, or superior, electronic characteristics and tribological performance.
{"title":"Ultrafast and scalable materials synthesis with flash-within-flash Joule heating","authors":"","doi":"10.1038/s41557-024-01645-3","DOIUrl":"10.1038/s41557-024-01645-3","url":null,"abstract":"A method called flash-within-flash Joule heating (FWF) has been developed based on a dual reactor design, enabling the gram-scale synthesis of diverse inorganic materials within seconds. Comparison with commercially available materials suggests that FWF products can offer comparable, or superior, electronic characteristics and tribological performance.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1753-1754"},"PeriodicalIF":19.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291592","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}
Boron dipyrromethenes (BODIPYs) are some of the most popular and indispensable tetracoordinate boron compounds and have found widespread applications owing to their excellent spectroscopic and photophysical properties. BODIPYs possessing boron-stereogenic centres are scarce, and strategies for the synthesis of enantioenriched boron-stereogenic BODIPYs with structural diversity remain underdeveloped. In theory, the BODIPY core skeleton has several sites that could be decorated with different substituents. However, due to the lack of general and efficient asymmetric synthetic methods, this potential diversity of chiral BODIPYs has not been exploited. Here we demonstrate a modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs in high efficiency with excellent enantioselectivities. Key to the success is the Pd-catalysed desymmetric Suzuki cross-coupling, enabling the precise discrimination of the two α C–Cl bonds of the designed prochiral BODIPY scaffold, giving access to a wide range of highly functionalized boron-stereogenic BODIPYs. Derivatizations, photophysical properties and applications in chiral recognition of the obtained optical BODIPYs are further explored. Boron dipyrromethenes (BODIPYs) have found widespread applications owing to their spectroscopic and photophysical properties, but strategies for the synthesis of enantioenriched boron-stereogenic BODIPYs are lacking. Now a modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs via a Pd-catalysed desymmetric Suzuki coupling has been developed, giving access to a range of highly functionalized chiral BODIPYs.
{"title":"Modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs","authors":"Li-Qing Ren, Baoquan Zhan, Jiayi Zhao, Yonghong Guo, Bing Zu, Yingzi Li, Chuan He","doi":"10.1038/s41557-024-01649-z","DOIUrl":"10.1038/s41557-024-01649-z","url":null,"abstract":"Boron dipyrromethenes (BODIPYs) are some of the most popular and indispensable tetracoordinate boron compounds and have found widespread applications owing to their excellent spectroscopic and photophysical properties. BODIPYs possessing boron-stereogenic centres are scarce, and strategies for the synthesis of enantioenriched boron-stereogenic BODIPYs with structural diversity remain underdeveloped. In theory, the BODIPY core skeleton has several sites that could be decorated with different substituents. However, due to the lack of general and efficient asymmetric synthetic methods, this potential diversity of chiral BODIPYs has not been exploited. Here we demonstrate a modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs in high efficiency with excellent enantioselectivities. Key to the success is the Pd-catalysed desymmetric Suzuki cross-coupling, enabling the precise discrimination of the two α C–Cl bonds of the designed prochiral BODIPY scaffold, giving access to a wide range of highly functionalized boron-stereogenic BODIPYs. Derivatizations, photophysical properties and applications in chiral recognition of the obtained optical BODIPYs are further explored. Boron dipyrromethenes (BODIPYs) have found widespread applications owing to their spectroscopic and photophysical properties, but strategies for the synthesis of enantioenriched boron-stereogenic BODIPYs are lacking. Now a modular enantioselective assembly of multi-substituted boron-stereogenic BODIPYs via a Pd-catalysed desymmetric Suzuki coupling has been developed, giving access to a range of highly functionalized chiral BODIPYs.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"17 1","pages":"83-91"},"PeriodicalIF":19.2,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291591","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 : 2024-09-18DOI: 10.1038/s41557-024-01596-9
Yohei Morishita, Suze Ma, Eugenio De La Mora, He Li, Heng Chen, Xinjian Ji, Anthony Usclat, Patricia Amara, Ryosuke Sugiyama, Yi Wei Tooh, Gregory Gunawan, Julien Pérard, Yvain Nicolet, Qi Zhang, Brandon I. Morinaka
Two of nature’s recurring binding motifs in metalloproteins are the CxxxCxxC motif in radical SAM enzymes and the 2-His-1-carboxylate motif found both in zincins and α-ketoglutarate and non-haem iron enzymes. Here we show the confluence of these two domains in a single post-translational modifying enzyme containing an N-terminal radical S-adenosylmethionine domain fused to a C-terminal 2-His-1-carboxylate (HExxH) domain. The radical SAM domain catalyses three-residue cyclophane formation and is the signature modification of triceptides, a class of ribosomally synthesized and post-translationally modified peptides. The HExxH domain is a defining feature of zinc metalloproteases. Yet the HExxH motif-containing domain studied here catalyses β-hydroxylation and is an α-ketoglutarate non-haem iron enzyme. We determined the crystal structure for this HExxH protein at 2.8 Å, unveiling a distinct structural fold, thus expanding the family of α-ketoglutarate non-haem iron enzymes with a class that we propose to name αKG-HExxH. αKG-HExxH proteins represent a unique family of ribosomally synthesized and post-translationally modified peptide modifying enzymes that can furnish opportunities for genome mining, synthetic biology and enzymology. Radical SAM (rSAM) and 2-His-1-carboxylate enzymes are known to co-occur in RiPP biosynthetic pathways. Here we show the fusion of these enzymes in a single protein where the rSAM enzyme catalyzes cyclophane formation. The 2-His-1-carboxylate enzymes—termed αKG-HExxH—are α-ketoglutarate non-haem iron enzymes that harbour a distinct fold and catalyse β-hydroxylation.
在金属蛋白中，有两个自然界反复出现的结合基团，一个是自由基 SAM 酶中的 CxxxCxxC 基团，另一个是在锌蛋白和 α-酮戊二酸及非血铁酶中发现的 2-His-1-羧酸基团。在这里，我们展示了这两个结构域在一个单一的翻译后修饰酶中的融合，该酶包含一个 N 端自由基 S-腺苷蛋氨酸结构域和一个 C 端 2-His-1-羧酸（HExxH）结构域。自由基 SAM 结构域催化三残基环烷的形成，是三肽这种由核糖体合成并经翻译后修饰的肽类的标志性修饰。HExxH 结构域是锌金属蛋白酶的一个显著特征。然而，本文研究的含 HExxH 主题结构域可催化β-羟基化反应，是一种α-酮戊二酸非血铁酶。我们测定了这种 HExxH 蛋白 2.8 Å 的晶体结构，揭示了一个独特的结构折叠，从而扩展了α-酮戊二酸非血红素铁酶家族，我们建议将其命名为αKG-HExxH。
{"title":"Fused radical SAM and αKG-HExxH domain proteins contain a distinct structural fold and catalyse cyclophane formation and β-hydroxylation","authors":"Yohei Morishita, Suze Ma, Eugenio De La Mora, He Li, Heng Chen, Xinjian Ji, Anthony Usclat, Patricia Amara, Ryosuke Sugiyama, Yi Wei Tooh, Gregory Gunawan, Julien Pérard, Yvain Nicolet, Qi Zhang, Brandon I. Morinaka","doi":"10.1038/s41557-024-01596-9","DOIUrl":"10.1038/s41557-024-01596-9","url":null,"abstract":"Two of nature’s recurring binding motifs in metalloproteins are the CxxxCxxC motif in radical SAM enzymes and the 2-His-1-carboxylate motif found both in zincins and α-ketoglutarate and non-haem iron enzymes. Here we show the confluence of these two domains in a single post-translational modifying enzyme containing an N-terminal radical S-adenosylmethionine domain fused to a C-terminal 2-His-1-carboxylate (HExxH) domain. The radical SAM domain catalyses three-residue cyclophane formation and is the signature modification of triceptides, a class of ribosomally synthesized and post-translationally modified peptides. The HExxH domain is a defining feature of zinc metalloproteases. Yet the HExxH motif-containing domain studied here catalyses β-hydroxylation and is an α-ketoglutarate non-haem iron enzyme. We determined the crystal structure for this HExxH protein at 2.8 Å, unveiling a distinct structural fold, thus expanding the family of α-ketoglutarate non-haem iron enzymes with a class that we propose to name αKG-HExxH. αKG-HExxH proteins represent a unique family of ribosomally synthesized and post-translationally modified peptide modifying enzymes that can furnish opportunities for genome mining, synthetic biology and enzymology. Radical SAM (rSAM) and 2-His-1-carboxylate enzymes are known to co-occur in RiPP biosynthetic pathways. Here we show the fusion of these enzymes in a single protein where the rSAM enzyme catalyzes cyclophane formation. The 2-His-1-carboxylate enzymes—termed αKG-HExxH—are α-ketoglutarate non-haem iron enzymes that harbour a distinct fold and catalyse β-hydroxylation.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 11","pages":"1882-1893"},"PeriodicalIF":19.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236848","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 : 2024-09-16DOI: 10.1038/s41557-024-01603-z
Sanjoy Adak, Naike Ye, Logan A. Calderone, Meng Duan, Wilson Lubeck, Rebecca J. B. Schäfer, April L. Lukowski, K. N. Houk, Maria-Eirini Pandelia, Catherine L. Drennan, Bradley S. Moore
Nitriles are uncommon in nature and are typically constructed from oximes through the oxidative decarboxylation of amino acid substrates or from the derivatization of carboxylic acids. Here we report a third nitrile biosynthesis strategy featuring the cyanobacterial nitrile synthase AetD. During the biosynthesis of the eagle-killing neurotoxin, aetokthonotoxin, AetD transforms the 2-aminopropionate portion of 5,7-dibromo-l-tryptophan to a nitrile. Employing a combination of structural, biochemical and biophysical techniques, we characterized AetD as a non-haem diiron enzyme that belongs to the emerging haem-oxygenase-like dimetal oxidase superfamily. High-resolution crystal structures of AetD together with the identification of catalytically relevant products provide mechanistic insights into how AetD affords this unique transformation, which we propose proceeds via an aziridine intermediate. Our work presents a unique template for nitrile biogenesis and portrays a substrate binding and metallocofactor assembly mechanism that may be shared among other haem-oxygenase-like dimetal oxidase enzymes. Nitrile-containing molecules and their biosynthetic enzymes are uncommon in nature. Now, a nitrile-forming diiron enzyme involved in the biosynthesis of aetokthonotoxin—the ‘eagle-killing’ neurotoxin—has been characterized using biochemical, structural and biophysical methods. High-resolution protein crystal structures together with the identification of catalytically relevant tryptophan-based products provide mechanistic insights into this unusual nitrile-forming reaction.
{"title":"A single diiron enzyme catalyses the oxidative rearrangement of tryptophan to indole nitrile","authors":"Sanjoy Adak, Naike Ye, Logan A. Calderone, Meng Duan, Wilson Lubeck, Rebecca J. B. Schäfer, April L. Lukowski, K. N. Houk, Maria-Eirini Pandelia, Catherine L. Drennan, Bradley S. Moore","doi":"10.1038/s41557-024-01603-z","DOIUrl":"10.1038/s41557-024-01603-z","url":null,"abstract":"Nitriles are uncommon in nature and are typically constructed from oximes through the oxidative decarboxylation of amino acid substrates or from the derivatization of carboxylic acids. Here we report a third nitrile biosynthesis strategy featuring the cyanobacterial nitrile synthase AetD. During the biosynthesis of the eagle-killing neurotoxin, aetokthonotoxin, AetD transforms the 2-aminopropionate portion of 5,7-dibromo-l-tryptophan to a nitrile. Employing a combination of structural, biochemical and biophysical techniques, we characterized AetD as a non-haem diiron enzyme that belongs to the emerging haem-oxygenase-like dimetal oxidase superfamily. High-resolution crystal structures of AetD together with the identification of catalytically relevant products provide mechanistic insights into how AetD affords this unique transformation, which we propose proceeds via an aziridine intermediate. Our work presents a unique template for nitrile biogenesis and portrays a substrate binding and metallocofactor assembly mechanism that may be shared among other haem-oxygenase-like dimetal oxidase enzymes. Nitrile-containing molecules and their biosynthetic enzymes are uncommon in nature. Now, a nitrile-forming diiron enzyme involved in the biosynthesis of aetokthonotoxin—the ‘eagle-killing’ neurotoxin—has been characterized using biochemical, structural and biophysical methods. High-resolution protein crystal structures together with the identification of catalytically relevant tryptophan-based products provide mechanistic insights into this unusual nitrile-forming reaction.","PeriodicalId":18909,"journal":{"name":"Nature chemistry","volume":"16 12","pages":"1989-1998"},"PeriodicalIF":19.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41557-024-01603-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234493","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}
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