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Oncogenic p53 triggers amyloid aggregation of p63 and p73 liquid droplets 致癌 p53 触发 p63 和 p73 液滴的淀粉样聚集
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-16 DOI: 10.1038/s42004-024-01289-x
Elaine C. Petronilho, Guilherme C. de Andrade, Gileno dos S. de Sousa, Fernando P. Almeida, Michelle F. Mota, Ana Vitória dos S. Gomes, Carlos Henrique S. Pinheiro, Mylena C. da Silva, Hiam R. S. Arruda, Mayra A. Marques, Tuane C. R. G. Vieira, Guilherme A. P. de Oliveira, Jerson L. Silva
{"title":"Oncogenic p53 triggers amyloid aggregation of p63 and p73 liquid droplets","authors":"Elaine C. Petronilho, Guilherme C. de Andrade, Gileno dos S. de Sousa, Fernando P. Almeida, Michelle F. Mota, Ana Vitória dos S. Gomes, Carlos Henrique S. Pinheiro, Mylena C. da Silva, Hiam R. S. Arruda, Mayra A. Marques, Tuane C. R. G. Vieira, Guilherme A. P. de Oliveira, Jerson L. Silva","doi":"10.1038/s42004-024-01289-x","DOIUrl":"10.1038/s42004-024-01289-x","url":null,"abstract":"P53 Phase separation is crucial towards amyloid aggregation and p63 and p73 have enhanced expression in tumors. This study examines the phase behaviors of p53, p63, and p73. Here we show that unlike the DNA-binding domain of p53 (p53C), the p63C and p73C undergo phase separation, but do not form amyloids under physiological temperatures. Wild-type and mutant p53C form droplets at 4°C and aggregates at 37 °C with amyloid properties. Mutant p53C promotes amyloid-like states in p63C and p73C, recruiting them into membraneless organelles. Amyloid conversion is supported by thioflavin T and Congo red binding, increased light scattering, and circular dichroism. Full-length mutant p53 and p63C (or p73C) co-transfection shows reduced fluorescence recovery after photobleaching. Heparin inhibits the prion-like aggregation of p63C and p73C induced by p53C. These findings highlight the role of p53 in initiating amyloid aggregation in p63 and p73, opening avenues for targeting prion-like conversion in cancer therapy. Phase separation of p53 is crucial in its progression towards amyloid aggregation, while its paralogous forms p63 and p73 have enhanced expression in tumors but reduced aggregation propensity. Here, the authors report the prion-like aggregation of p63 and p73 mediated by p53 and outline that this process can be inhibited by heparin.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":5.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01289-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeted sulfur(VI) fluoride exchange-mediated covalent modification of a tyrosine residue in the catalytic pocket of tyrosyl-DNA phosphodiesterase 1 以氟化硫(VI)交换为介导,对酪氨酸-DNA 磷酸二酯酶 1 催化口袋中的一个酪氨酸残基进行靶向共价修饰
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-16 DOI: 10.1038/s42004-024-01298-w
Xue Zhi Zhao, Idris A. Barakat, George T. Lountos, Wenjie Wang, Keli Agama, Md Rasel Al Mahmud, Kiall F. Suazo, Thorkell Andresson, Yves Pommier, Terrence R. Burke Jr.
{"title":"Targeted sulfur(VI) fluoride exchange-mediated covalent modification of a tyrosine residue in the catalytic pocket of tyrosyl-DNA phosphodiesterase 1","authors":"Xue Zhi Zhao, Idris A. Barakat, George T. Lountos, Wenjie Wang, Keli Agama, Md Rasel Al Mahmud, Kiall F. Suazo, Thorkell Andresson, Yves Pommier, Terrence R. Burke Jr.","doi":"10.1038/s42004-024-01298-w","DOIUrl":"10.1038/s42004-024-01298-w","url":null,"abstract":"Developing effective inhibitors of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) has been challenging because of the enzyme shallow catalytic pocket and non-specific substrate binding interactions. Recently, we discovered a quinolone-binding hot spot in TDP1’s active site proximal to the evolutionary conserved Y204 and F259 residues that position DNA. Sulfur (VI) fluoride exchange (SuFEx) is a biocompatible click chemistry reaction that enables acylation of protein residues, including tyrosine. Selective protein modifications can provide insights into the biological roles of proteins and inform ligand design. As we report herein, we used SuFEx chemistries to prepare covalent TDP1-bound binders showing site-specific covalent bonds with Y204. Our work presents the first application of SuFEx chemistries to TDP1 ligands. It validates the ability to covalently modify specific TDP1 residues by designed targeting and adds to the chemical biology resource toolbox for studying TDP1. Developing effective inhibitors of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) is challenging because of the enzyme’s shallow catalytic pocket and non-specific substrate binding interactions. Here, the authors use Sulfur (VI) fluoride exchange chemistries to prepare covalent TDP1-bound binders showing site-specific covalent bonds with the Y204 residue that position DNA.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-13"},"PeriodicalIF":5.9,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01298-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interaction and dynamics of chemokine receptor CXCR4 binding with CXCL12 and hBD-3 趋化因子受体 CXCR4 与 CXCL12 和 hBD-3 的相互作用和动态结合
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-13 DOI: 10.1038/s42004-024-01280-6
Jackson Penfield, Liqun Zhang
{"title":"Interaction and dynamics of chemokine receptor CXCR4 binding with CXCL12 and hBD-3","authors":"Jackson Penfield, Liqun Zhang","doi":"10.1038/s42004-024-01280-6","DOIUrl":"10.1038/s42004-024-01280-6","url":null,"abstract":"Chemokine receptor CXCR4 is involved in diverse diseases. A comparative study was conducted on CXCR4 embedded in a POPC lipid bilayer binding with CXCL12 in full and truncated forms, hBD-3 in wildtype, analog, and mutant forms based on in total 63 µs all-atom MD simulations. The initial binding structures of CXCR4 with ligands were predicted using HADDOCK docking or random-seed method, then μs-long simulations were performed to refine the structures. CXCR4&ligand binding structures predicted agree with available literature data. Both kinds of ligands bind stably to the N-terminus, extracellular loop 2 (ECL2), and ECL3 regions of CXCR4; the C2-C3 (K32-R38) region and occasionally the head of hBD-3 bind stably with CXCR4. hBD-3 analogs with Cys11-Cys40 disulfide bond can activate CXCR4 based on the Helix3-Helix6 distance calculation, but not other analogs or mutant. The results provide insight into understanding the dynamics and activation mechanism of CXCR4 receptor binding with different ligands. The chemokine receptor CXCR4 is involved in cancers and diverse diseases, however, molecular details surrounding the binding of different ligands to this receptor remain incomplete. Here, the authors study the binding and interaction between CXCR4 with CXCL12 and hBD-3 in different forms, and find that both ligands can bind with CXCR4 at the same site, and analogs of hBD-3 with a Cys11-Cys40 disulfide bond can activate CXCR4.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":5.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01280-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Interface potential-induced natural antioxidant mimic system for the treatment of Alzheimer’s disease 用于治疗阿尔茨海默病的界面电位诱导天然抗氧化剂模拟系统
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-13 DOI: 10.1038/s42004-024-01299-9
Kangning Liu, Qi Ding, Doudou Cao, Enpeng Xi, Yun Zhao, Nan Gao, Yajie Yang, Ye Yuan
{"title":"Interface potential-induced natural antioxidant mimic system for the treatment of Alzheimer’s disease","authors":"Kangning Liu, Qi Ding, Doudou Cao, Enpeng Xi, Yun Zhao, Nan Gao, Yajie Yang, Ye Yuan","doi":"10.1038/s42004-024-01299-9","DOIUrl":"10.1038/s42004-024-01299-9","url":null,"abstract":"Although the pathogenesis of Alzheimer’s disease (AD) is still unknown, the molecular pathological phenomena is clear, mainly due to mitochondrial dysfunction and central nervous system inflammation caused by imbalanced antioxidant capacity and synaptic dysfunction, so antioxidant therapy is still the preferred treatment for AD. However, although antioxidant enzymes have high catalytic efficiency, the substrate spectrum is narrow; Antioxidants have wider range of effects, but their efficiency is low. Since the antioxidant defense system in high-grade organisms is composed of both enzymatic and non-enzymatic systems, therefore we synthesized a metal-organic framework (MOF) with superoxide dismutase activity, and depending on the interface potential effect, curcumin was loaded to construct a synergistic antioxidant treatment system. More importantly, due to the complementary surface electrostatic potential between MOF and curcumin, the system exhibited both good antioxidant activity and efficient β-amyloid plaque scavenging ability, which slowed down the cognitive dysfunction in the brain of AD mice. Although the pathogenesis of Alzheimer’s disease (AD) is still unknown, imbalanced antioxidant capacity in nerve cells is a successfully targeted pathological phenomenon in clinical practice. Here, the authors show that the complementary surface electrostatic potential between a metal-organic framework and curcumin results in a complex with good antioxidant activity and efficient β-amyloid plaque scavenging ability, which slows down the cognitive dysfunction in the brain of AD mice.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-6"},"PeriodicalIF":5.9,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01299-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Total synthesis of a structurally complex zwitterionic hexasaccharide repeating unit of polysaccharide B from Bacteroides fragilis via one-pot glycosylation 通过一次糖基化全合成结构复杂的脆弱拟杆菌多糖 B 的齐聚物六糖重复单元
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-12 DOI: 10.1038/s42004-024-01296-y
Krishna Puri, Suvarn S. Kulkarni
{"title":"Total synthesis of a structurally complex zwitterionic hexasaccharide repeating unit of polysaccharide B from Bacteroides fragilis via one-pot glycosylation","authors":"Krishna Puri, Suvarn S. Kulkarni","doi":"10.1038/s42004-024-01296-y","DOIUrl":"10.1038/s42004-024-01296-y","url":null,"abstract":"Zwitterionic polysaccharides (ZPSs) present on the surface of a common gut commensal Bacteroides fragilis are endowed with unique immunological properties as they can directly bind to T-cells in the absence of protein conjugation. ZPSs are therefore considered to be potential antigens for the development of totally carbohydrate-based vaccines. Herein, we disclose the first total synthesis of a highly branched phosphorylated zwitterionic capsular polysaccharide repeating unit of Bacteroides fragilis. The hexasaccharide repeating unit bearing six different monosaccharides comprises three 1,2-cis-glycosidic linkages, a challenging 1,2-trans linkage in D-QuipNAc-β-(1→4)-D-Gal motif, and a 2-aminoethyl phosphonate appendage. The synthesis of target ZPS was accomplished utilizing an expeditious, highly stereoselective and convergent (1 + 2 + 2 + 1) one-pot glycosylation strategy. The striking features include efficient synthesis of rare deoxy amino sugars D- and L-quinovosamine, stereoselective installation of three 1,2-cis glycosidic linkages, glycosylation of D-quinovosamine donor with a sterically crowded, poorly reactive 4-OH galactose moiety, as well as late stage phosphorylation. Zwitterionic polysaccharides present on the surface of a common gut commensal Bacteroides fragilis are considered to be potential antigens for the development of totally carbohydrate-based vaccines. Here, the authors report the total synthesis of a highly branched phosphorylated zwitterionic capsular hexasaccharide repeating unit of Bacteroides fragilis via a one-pot glycosylation strategy.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-15"},"PeriodicalIF":5.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01296-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Direct glycosylation analysis of intact monoclonal antibodies combining ESI MS of glycoforms and MALDI-in source decay MS of glycan fragments 结合糖形的 ESI MS 和糖链片段的 MALDI-in source decay MS,对完整单克隆抗体进行直接糖基化分析
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-12 DOI: 10.1038/s42004-024-01297-x
Isabella Senini, Sara Tengattini, Francesca Rinaldi, Gabriella Massolini, Christoph Gstöttner, Dietmar Reusch, Marcello Donini, Carla Marusic, Peter A. van Veelen, Elena Domínguez-Vega, Manfred Wuhrer, Caterina Temporini, Simone Nicolardi
{"title":"Direct glycosylation analysis of intact monoclonal antibodies combining ESI MS of glycoforms and MALDI-in source decay MS of glycan fragments","authors":"Isabella Senini, Sara Tengattini, Francesca Rinaldi, Gabriella Massolini, Christoph Gstöttner, Dietmar Reusch, Marcello Donini, Carla Marusic, Peter A. van Veelen, Elena Domínguez-Vega, Manfred Wuhrer, Caterina Temporini, Simone Nicolardi","doi":"10.1038/s42004-024-01297-x","DOIUrl":"10.1038/s42004-024-01297-x","url":null,"abstract":"Monoclonal antibody (mAb) glycoengineering has the potential to improve the efficacy of biopharmaceuticals by fine-tuning specific biological properties. Glycosylation analysis is key to monitoring the glycoengineering process. Various mass spectrometry (MS)-based methods are available to characterize mAb glycosylation at different structural levels, but comprehensive analysis is typically time-consuming and costly. Here, we present an approach that combines conventional intact mass measurement of glycoforms by direct infusion ESI-MS with an advanced MALDI-in-source decay FT-ICR MS method for direct analysis of glycans in intact mAbs, without the need for enzymatic release and separation. Using a sodium-doped MALDI matrix, glycans were directly released as ISD fragment ions from the intact mAbs during the ionization process. Measurement of 0,2A fragment signals yielded reproducible glycan profiles that were consistent with conventional methods, yet was achieved with unprecedented speed, providing complementary information to that obtained through intact mass measurement. The methods were applied to standard and glycoengineered trastuzumab and rituximab, allowing rapid glycosylation profiling and structural analysis of glycans by tandem MS of selected ISD fragment ions. This fast approach can facilitate the early-phase development of glycoengineering processes by constraining further in-depth analyses. We envision a broader applicability in studies focused on glycosylation changes in mAbs. Glycoengineering of monoclonal antibodies (mAbs) has the potential to improve the efficacy of biopharmaceuticals, however, monitoring the glycoengineering process by glycosylation analysis often requires a multi-method approach. Here, the authors present a direct glycosylation analysis of intact mAbs by combining conventional ESI-MS of intact glycoforms and MALDI-in-source decay FT-ICR MS of glycan fragments.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01297-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142210250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of ketalized unsaturated saccharides as multifunctional cysteine-targeting covalent warheads 开发酮化不饱和糖作为多功能半胱氨酸靶向共价弹头
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-09 DOI: 10.1038/s42004-024-01279-z
Sanfeng Dong, Hui Huang, Jintian Li, Xiaomei Li, Samuel Jacob Bunu, Yun Yang, Yong Zhang, Qi Jia, Zhijian Xu, Yingxia Li, Hu Zhou, Bo Li, Weiliang Zhu
{"title":"Development of ketalized unsaturated saccharides as multifunctional cysteine-targeting covalent warheads","authors":"Sanfeng Dong, Hui Huang, Jintian Li, Xiaomei Li, Samuel Jacob Bunu, Yun Yang, Yong Zhang, Qi Jia, Zhijian Xu, Yingxia Li, Hu Zhou, Bo Li, Weiliang Zhu","doi":"10.1038/s42004-024-01279-z","DOIUrl":"10.1038/s42004-024-01279-z","url":null,"abstract":"Multi-functional cysteine-targeting covalent warheads possess significant therapeutic potential in medicinal chemistry and chemical biology. Herein, we present novel unsaturated and asymmetric ketone (oxazolinosene) scaffolds that selectively conjugate cysteine residues of peptides and bovine serum albumin under normal physiological conditions. This unsaturated saccharide depletes GSH in NCI-H1299 cells, leading to anti-tumor effects in vitro. The acetyl group of the ketal moiety on the saccharide ring can be converted to other carboxylic acids in a one-pot synthesis. In this way, the loaded acid can be click-released during cysteine conjugation, making the oxazolinosene a potential multifunctional therapeutic agent. The reaction kinetic model for oxazolinosene conjugation to GSH is well established and was used to evaluate oxazolinosene reactivity. The aforementioned oxazolinosenes were stereoselectively synthesized via a one-step reaction of nitriles with saccharides and conveniently converted into a series of α, β-unsaturated ketone N-glycosides as prevalent synthetic building blocks. The reaction mechanisms of oxazolinosene synthesis were investigated through calculations and validated with control experiments. Overall, these oxazolinosenes can be easily synthesized and developed as cysteine-targeted covalent warheads carrying useful click-releasing groups. Multifunctional cysteine targeting covalent warheads possess significant therapeutic potential in medicinal chemistry and chemical biology. Here, the authors develop an oxazolinosene scaffold from nitrile groups and saccharides that can selectively conjugate cysteine residues within peptides and proteins under physiological conditions, as well as deplete glutathione in cancer cells.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-10"},"PeriodicalIF":5.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01279-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Regulating the photoluminescence of aluminium complexes from non-luminescence to room-temperature phosphorescence by tuning the metal substituents 通过调整金属取代基调节铝络合物的光致发光,使其从非发光状态转变为室温磷光状态
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-09 DOI: 10.1038/s42004-024-01295-z
Shunichiro Ito, Takuya Hosokai, Kazuo Tanaka, Yoshiki Chujo
{"title":"Regulating the photoluminescence of aluminium complexes from non-luminescence to room-temperature phosphorescence by tuning the metal substituents","authors":"Shunichiro Ito, Takuya Hosokai, Kazuo Tanaka, Yoshiki Chujo","doi":"10.1038/s42004-024-01295-z","DOIUrl":"10.1038/s42004-024-01295-z","url":null,"abstract":"Although luminescent aluminum compounds have been utilized for emitting and electron transporting layers in organic light-emitting diodes, most of them often exhibit not phosphorescence but fluorescence with lower photoluminescent quantum yields in the aggregated state than those in the amorphous state due to concentration quenching. Here we show the synthesis and optical properties of β-diketiminate aluminum complexes, such as crystallization-induced emission (CIE) and room-temperature phosphorescence (RTP), and the substituent effects of the central element. The dihaloaluminum complexes were found to exhibit the CIE property, especially RTP from the diiodo complex, while the dialkyl ones showed almost no emission in both solution and solid states. Theoretical calculations suggested that undesired structural relaxation in the singlet excited state of dialkyl complexes should be suppressed by introducing electronegative halogens instead of alkyl groups. Our findings could provide a molecular design not only for obtaining luminescent complexes but also for achieving triplet-harvesting materials. Luminescent aluminum compounds have been utilized for emitting and electron transporting layers in organic light-emitting diodes, but most exhibit fluorescence as opposed to phosphorescence. Here, the photophysical properties of β-diketiminate aluminum complexes are shown to depend on the nature of the metal substituents, with a diiodoaluminum complex displaying room temperature phosphorescence.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-9"},"PeriodicalIF":5.9,"publicationDate":"2024-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01295-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
H2-driven biocatalysis for flavin-dependent ene-reduction in a continuous closed-loop flow system utilizing H2 from water electrolysis 利用水电解产生的 H2,在连续闭环流动系统中进行黄素依赖性烯还原的 H2 驱动生物催化反应。
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-07 DOI: 10.1038/s42004-024-01288-y
Guiyeoul Lim, Donato Calabrese, Allison Wolder, Paul R. F. Cordero, Dörte Rother, Florian F. Mulks, Caroline E. Paul, Lars Lauterbach
{"title":"H2-driven biocatalysis for flavin-dependent ene-reduction in a continuous closed-loop flow system utilizing H2 from water electrolysis","authors":"Guiyeoul Lim, Donato Calabrese, Allison Wolder, Paul R. F. Cordero, Dörte Rother, Florian F. Mulks, Caroline E. Paul, Lars Lauterbach","doi":"10.1038/s42004-024-01288-y","DOIUrl":"10.1038/s42004-024-01288-y","url":null,"abstract":"Despite the increasing demand for efficient and sustainable chemical processes, the development of scalable systems using biocatalysis for fine chemical production remains a significant challenge. We have developed a scalable flow system using immobilized enzymes to facilitate flavin-dependent biocatalysis, targeting as a proof-of-concept asymmetric alkene reduction. The system integrates a flavin-dependent Old Yellow Enzyme (OYE) and a soluble hydrogenase to enable H2-driven regeneration of the OYE cofactor FMNH2. Molecular hydrogen was produced by water electrolysis using a proton exchange membrane (PEM) electrolyzer and introduced into the flow system via a designed gas membrane addition module at a high diffusion rate. The flow system shows remarkable stability and reusability, consistently achieving >99% conversion of ketoisophorone to levodione. It also demonstrates versatility and selectivity in reducing various cyclic enones and can be extended to further flavin-based biocatalytic approaches and gas-dependent reactions. This electro-driven continuous flow system, therefore, has significant potential for advancing sustainable processes in fine chemical synthesis. Flavin-based biocatalysis using flavin mononucleotide (FMN) cofactor attracts significant attention for its application in asymmetric alkene reduction and various other reactions, however, the scale-up of flavin-based biocatalysis in flow remains unexplored. Here, the authors develop a closed-loop flow platform for H2-driven regeneration of cofactor FMNH2 and ene-reduction using immobilized Old Yellow Enzyme, achieving >99% conversion of ketoisophorone to levodione.","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":" ","pages":"1-7"},"PeriodicalIF":5.9,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s42004-024-01288-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elastin-like polypeptide coacervates as reversibly triggerable compartments for synthetic cells 弹性蛋白样多肽凝聚物作为合成细胞的可逆触发隔室
IF 5.9 2区 化学
Communications Chemistry Pub Date : 2024-09-04 DOI: 10.1038/s42004-024-01270-8
Chang Chen, Ketan A. Ganar, Robbert J. de Haas, Nele Jarnot, Erwin Hogeveen, Renko de Vries, Siddharth Deshpande
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