Nature chemical biology最新文献_第8页

How ocean enzymes are providing access to understudied cannabinoids. 海洋酶如何提供未被充分研究的大麻素。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-08-11 DOI: 10.1038/s41589-026-02298-8

引用次数: 0

Metabolic reprogramming drives pancreatic β cell neogenesis from α cells. 代谢重编程驱动胰腺β细胞从α细胞新生。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-08-07 DOI: 10.1038/s41589-026-02293-z

Yufeng Zhang, Guangxing Lu, Wenhao Xie, Peng Xu, Cenxi Liu, Olga Babosova, Jamie Christopher Reilly, Zhehui Li, Leshi Chen, Liying Zhou, Jing Gao, Lennart Enders, Xuelian Xiong, Mingyu Li, Stefan Kubicek, Bing Zhao, Zhe Feng, Biao Yu, Lu Zhou, He Huang, Jin Li

{"title":"Metabolic reprogramming drives pancreatic β cell neogenesis from α cells.","authors":"Yufeng Zhang, Guangxing Lu, Wenhao Xie, Peng Xu, Cenxi Liu, Olga Babosova, Jamie Christopher Reilly, Zhehui Li, Leshi Chen, Liying Zhou, Jing Gao, Lennart Enders, Xuelian Xiong, Mingyu Li, Stefan Kubicek, Bing Zhao, Zhe Feng, Biao Yu, Lu Zhou, He Huang, Jin Li","doi":"10.1038/s41589-026-02293-z","DOIUrl":"10.1038/s41589-026-02293-z","url":null,"abstract":"Loss of functional β cells is a hallmark of diabetes, and restoring β cell mass remains a critical goal in the quest for a specific therapy. One potential strategy is to convert non-β cells in the islet, such as α cells, into insulin-producing cells. Although several compounds have been identified to induce β cell-like features in α cells, none have been successfully translated into clinical applications. In this study, we identify PRC2 inhibitors as potent inducers of β cell-enriched gene expression in α cells, acting through modulation of the AR-ETV1 complex. AR inhibition suppresses glycogen synthesis and enhances the pentose phosphate pathway. Direct metabolic reprogramming with methyl esterified 6-phosphogluconate, an intermediate metabolite of the pentose phosphate pathway, induces β cell-like features in α cells, stimulates β cell regeneration and ameliorates diabetes. Our findings demonstrate that metabolic reprogramming drives β cell regeneration and highlight a promising therapeutic strategy for diabetes.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689489","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A covalent PFKL activator suppresses tumor growth 一种共价PFKL激活剂抑制肿瘤生长。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-08-05 DOI: 10.1038/s41589-026-02289-9

Xiaoding Jiang, Eric M. Lynch, Congcong Lyu, Crystal N. Wilson, Lauren E. Salay, Hayden T. Hess, Scott N. Lyons, Mu-Jie Lu, Shuangyu Luo, Gibae Kim, Hsin-Ru Chan, Wesley J. Wolfe, Lauren G. Zacharias, Thomas P. Mathews, Yi-Chih Lin, Bradley A. Webb, Justin M. Kollman, Xiaolu A. Cambronne, Ku-Lung Hsu

{"title":"A covalent PFKL activator suppresses tumor growth","authors":"Xiaoding Jiang, Eric M. Lynch, Congcong Lyu, Crystal N. Wilson, Lauren E. Salay, Hayden T. Hess, Scott N. Lyons, Mu-Jie Lu, Shuangyu Luo, Gibae Kim, Hsin-Ru Chan, Wesley J. Wolfe, Lauren G. Zacharias, Thomas P. Mathews, Yi-Chih Lin, Bradley A. Webb, Justin M. Kollman, Xiaolu A. Cambronne, Ku-Lung Hsu","doi":"10.1038/s41589-026-02289-9","DOIUrl":"10.1038/s41589-026-02289-9","url":null,"abstract":"Glycolysis fuels vital cellular functions, and its dysregulation has been implicated in cancer, neurodegeneration, antibiotic resistance and diabetes. The glycolytic dependency of cancer, known as the Warburg effect, represents a key vulnerability for development of targeted anticancer agents; however, the development of such agents remains challenging owing to metabolic heterogeneity and resistance. Here we developed a covalent phosphofructokinase-1 liver type (PFKL) activator that couples glycolytic activation with delivery of a cytotoxic carnitine palmitoyltransferase 2 (CPT2)-targeting payload to cancer cells in vitro and in vivo. The electrophile–drug conjugate site-specifically and proteome-wide selectively modifies K677 in the allosteric effector site to stabilize the R-state tetramer of PFKL, while concomitantly releasing a CPT2-selective inhibitor to destabilize cell metabolism. The delivery mechanism of electrophile–drug conjugates is analogous to that of antibody–drug conjugates, but differentiated by their selective covalent targeting of intracellular proteins. An electrophile–drug conjugate covalently activates PFKL through K677 engagement and releases a selective CPT2-targeting payload. This strategy exploits metabolic vulnerabilities to suppress tumor growth in vitro and in vivo.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"22 11","pages":"1843-1853"},"PeriodicalIF":15.8,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41589-026-02289-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging tools to investigate the contribution of selenium to ferroptosis and beyond. 新兴的工具来研究硒对铁下垂及其他方面的贡献。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-08-04 DOI: 10.1038/s41589-026-02278-y

Gholamreza Fazeli, Ihyeon Ahn, Michael D Pluth, Raphael E F de Paiva, Namgyu Lee, José Pedro Friedmann Angeli

引用次数: 0

Computational design of antimicrobial peptide nanopores. 抗菌肽纳米孔的计算设计。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-08-03 DOI: 10.1038/s41589-026-02269-z

Rahul Deb, Marcelo D T Torres, Ivo Kabelka, Jan Přibyl, Kateřina Dvořáková Bendová, Edo Vreeker, Markéta Koběrská, Gabriela Balíková Novotná, Miloš Petřík, Giovanni Maglia, Cesar de la Fuente-Nunez, Robert Vácha

{"title":"Computational design of antimicrobial peptide nanopores.","authors":"Rahul Deb, Marcelo D T Torres, Ivo Kabelka, Jan Přibyl, Kateřina Dvořáková Bendová, Edo Vreeker, Markéta Koběrská, Gabriela Balíková Novotná, Miloš Petřík, Giovanni Maglia, Cesar de la Fuente-Nunez, Robert Vácha","doi":"10.1038/s41589-026-02269-z","DOIUrl":"https://doi.org/10.1038/s41589-026-02269-z","url":null,"abstract":"Antibiotic resistance is a global health threat, driving the need for new molecules that kill bacteria via nontraditional mechanisms. Here, we present a computational de novo design strategy for α-helical peptides that self-assemble into large, stable and membrane-spanning nanopores with antimicrobial activity, including in vivo efficacy against drug-resistant pathogens. Molecular dynamics simulations guided the selection of sequences for transmembrane barrel-stave pore formation, which were validated by microscopy, electrophysiology and fluorescence assays. Using computational and experimental analyses, including negative design controls, we developed general design guidelines and 52 modular sequence templates with tunable antimicrobial, pore-forming properties. Mechanistic studies confirmed bacterial cytoplasmic membrane disruption via designed nanopore formation. A tuned lead peptide selectively killed drug-resistant ESKAPEE bacteria, including Acinetobacter baumannii, without harming human cells, and showed anti-infective efficacy in preclinical mouse infection models. The framework presented here enables the design of synthetic peptide nanopores for precision antimicrobials, anticancer agents, molecular sensors and delivery systems.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Black yeasts are efficient heterologous hosts for the production of a wide range of fungal polyketides. 黑酵母是生产多种真菌聚酮的高效异源宿主。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-08-03 DOI: 10.1038/s41589-026-02282-2

Adrian E Gadar-Lopez, Ana Calheiros de Carvalho, Xiaowei Li, Daniela Rago, Linda Ahonen, Charlotte H Gotfredsen, Marie V Lukassen, Carolina Cano-Prieto, Ling Chen, Sidharth Jayachandran, Jeppe S Brogaard, Miriam von Bargen, Laasya Bhagavan, Tomas Strucko, Adrian Krummenacher-Frey, Dushica Arsovska, Erin C Carr, Sheila I Jensen, Steven D Harris, Uffe H Mortensen, Jay D Keasling, Pablo Cruz-Morales

{"title":"Black yeasts are efficient heterologous hosts for the production of a wide range of fungal polyketides.","authors":"Adrian E Gadar-Lopez, Ana Calheiros de Carvalho, Xiaowei Li, Daniela Rago, Linda Ahonen, Charlotte H Gotfredsen, Marie V Lukassen, Carolina Cano-Prieto, Ling Chen, Sidharth Jayachandran, Jeppe S Brogaard, Miriam von Bargen, Laasya Bhagavan, Tomas Strucko, Adrian Krummenacher-Frey, Dushica Arsovska, Erin C Carr, Sheila I Jensen, Steven D Harris, Uffe H Mortensen, Jay D Keasling, Pablo Cruz-Morales","doi":"10.1038/s41589-026-02282-2","DOIUrl":"https://doi.org/10.1038/s41589-026-02282-2","url":null,"abstract":"Fungal polyketides are a rich source of bioactive molecules. Their biosynthesis is often activated by environmental conditions that are hard to reproduce under laboratory conditions. Heterologous expression bypasses native regulation, enabling systematic polyketide discovery. The most widely used fungal hosts are the highly tractable Saccharomycotina yeasts with a narrow product scope and the metabolically robust but less tractable filamentous Eurotiomycetes. Here we established yeasts of the genera Exophiala and Knufia as hosts for polyketide production. These hosts are genetically tractable and robust, allowing us to heterologously produce six fungal polyketides with different domain architectures: 6-methylsalicylic acid, YWA1, monocillin II, farinosone B and monacolin J. Our findings demonstrate that these yeast hosts can efficiently produce complex polyketides allowing systematic polyketide synthase expression.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":" ","pages":""},"PeriodicalIF":15.8,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Black yeasts emerge as hosts for fungal polyketide production. 黑酵母作为真菌聚酮生产的宿主出现。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-08-03 DOI: 10.1038/s41589-026-02223-z

Tahir Ali, Elizabeth Skellam

引用次数: 0

Expanding the repertoire of chemically induced covalent neoantigens 扩大化学诱导的共价新抗原的种类

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2026-07-30 DOI: 10.1038/s41589-026-02280-4

Chen Zhou, Xiaokang Jin, Wei Huang, Haofeng Wu, Lynn M. McGregor, Markus Schirle, Chenlu Zhang, Xiaoyu Zhang

{"title":"Expanding the repertoire of chemically induced covalent neoantigens","authors":"Chen Zhou, Xiaokang Jin, Wei Huang, Haofeng Wu, Lynn M. McGregor, Markus Schirle, Chenlu Zhang, Xiaoyu Zhang","doi":"10.1038/s41589-026-02280-4","DOIUrl":"https://doi.org/10.1038/s41589-026-02280-4","url":null,"abstract":"The ubiquitin–proteasome system generates peptide fragments that are displayed on class I major histocompatibility complex molecules. Hapten-modified peptides, or covalent neoantigens, arise from proteins covalently modified by small molecules and have long been proposed as components of a mechanism for immune recognition. Here we report a platform to investigate this mechanism and harness covalent neoantigens for immune cell recruitment and activation. Using cysteine-reactive probes, we demonstrated that covalently modified intracellular proteins could be processed and presented as covalent neoantigens in multiple cell lines. Immunopeptidomics confirmed the presence of probe-modified peptides within the class I major histocompatibility complex immunopeptidome. We further developed a bioorthogonal strategy for immune cell engagement by combining covalent neoantigens bearing a bioorthogonal handle with complementary immune cell recruiters, leading to activation of CD32- and CD3-expressing reporter immune cells. These findings expand the scope of covalent neoantigen formation and provide a generalizable strategy for immune targeting of covalent neoantigens.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"19 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148612697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

How tobacco builds nicotine. 烟草是如何产生尼古丁的。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-30 DOI: 10.1038/s41589-026-02281-3

Jing-Ke Weng

引用次数: 0

AI design of gut microbiomes 肠道微生物群的人工智能设计。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-27 DOI: 10.1038/s41589-026-02273-3

Daniel M. Ferrer, Mark Holton, Guillaume Urtecho

引用次数: 0