Nature chemical biology最新文献_第9页

Designing fiber–gut microbiome interactions with active learning 设计纤维-肠道微生物群与主动学习的相互作用。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-27 DOI: 10.1038/s41589-026-02272-4

Bryce M. Connors, Jaron Thompson, Manasi Subhash Gangan, Nick Quinn-Bohmann, Sean M. Gibbons, Job Grant, Alejandro Castellanos-Sanchez, Jessica R. McCann, John F. Rawls, Ophelia S. Venturelli

{"title":"Designing fiber–gut microbiome interactions with active learning","authors":"Bryce M. Connors, Jaron Thompson, Manasi Subhash Gangan, Nick Quinn-Bohmann, Sean M. Gibbons, Job Grant, Alejandro Castellanos-Sanchez, Jessica R. McCann, John F. Rawls, Ophelia S. Venturelli","doi":"10.1038/s41589-026-02272-4","DOIUrl":"10.1038/s41589-026-02272-4","url":null,"abstract":"Identifying synergies between dietary fibers and beneficial bacteria holds promise for precision interventions that optimize gut health, yet these interactions remain largely unexplored. Here we integrate machine learning, Bayesian optimization and high-throughput community construction to investigate how dietary fibers shape health-relevant functions of human gut microbial communities. To efficiently navigate the landscape of fiber–microbiome interactions, we implemented a design–test–learn cycle to identify fiber–species combinations that maximize a multiobjective function capturing beneficial community properties. Our model-guided approach revealed a highly butyrogenic and robust ecological motif characterized by the copresence of inulin, Bacteroides uniformis and Anaerostipes caccae and a higher-order interaction with Prevotella copri. Human fecal communities invaded with model-designed species–fiber combinations displayed predictable gut-beneficial outputs. In sum, we demonstrate a framework for designing synthetic microbial communities with desired functions in response to key nutrients. Dietary fibers are a primary energy source for gut bacteria and shape the composition and function of the microbiome. Now, an active learning approach integrating explainable machine learning, Bayesian optimization and high-throughput community construction designs microbial communities with desired functions in response to key nutrients.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"22 8","pages":"1286-1298"},"PeriodicalIF":15.8,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148605271","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

Computing complexity 计算的复杂性。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-27 DOI: 10.1038/s41589-026-02290-2

引用次数: 0

Using enantioselective biosensors to evolve asymmetric biocatalysts 利用对映选择性生物传感器进化不对称生物催化剂。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-23 DOI: 10.1038/s41589-026-02275-1

Simon d’Oelsnitz, Wantae Kim, Nicole N. Zhao, Haley Hardtke, Svetlana P. Ikonomova, Nina Alperovich, Olga Vasilyeva, Michael J. James, Eric S. Zigon, Michael B. Cory, Charlie D. Johnson, Andrew D. Ellington, Quincey A. Justman, Michael Springer, Y. Jessie Zhang, Pamela A. Silver, David Ross

{"title":"Using enantioselective biosensors to evolve asymmetric biocatalysts","authors":"Simon d’Oelsnitz, Wantae Kim, Nicole N. Zhao, Haley Hardtke, Svetlana P. Ikonomova, Nina Alperovich, Olga Vasilyeva, Michael J. James, Eric S. Zigon, Michael B. Cory, Charlie D. Johnson, Andrew D. Ellington, Quincey A. Justman, Michael Springer, Y. Jessie Zhang, Pamela A. Silver, David Ross","doi":"10.1038/s41589-026-02275-1","DOIUrl":"10.1038/s41589-026-02275-1","url":null,"abstract":"Biocatalysts are prized for their enantioselectivity, but slow chromatographic separations required to measure enantiomeric excess bottleneck their development. To overcome this limitation, we evolve enantioselective transcription factors (eTFs) that convert enzyme-catalyzed enantiomer concentrations into programmable gene expression outputs, focusing on imine reductases. Here, using a massively parallel reporter assay, we measure dose–response curves for over 300,000 transcription factor variants in response to an imine precursor and chiral amine products. We quantify the sensitivity, selectivity and dynamic range across variants generated by random, site-saturation and shuffling mutagenesis, isolating variants with exceptional specificity. High-resolution structures of evolved eTFs elucidate how steric effects enforce enantioselectivity, while charge interactions distinguish the imine from the amines. Using two eTFs, we create an ultrahigh-throughput chiral screen to evolve an imine reductase with inverted enantioselectivity. To support generalizability and speed, we design a genetic circuit that enables TF generation within weeks. Our methods enable rapid measurement of asymmetric reactions, supporting innovation in chemical manufacturing. Here d’Oelsnitz et al. generate enantioselective transcription factors that convert chiral reaction products into fluorescent signals, enabling the rapid evolution of asymmetric enzymes with inverted selectivity.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"22 11","pages":"1800-1809"},"PeriodicalIF":15.8,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41589-026-02275-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579363","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

Analyzing alternate translation 分析交替翻译。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-20 DOI: 10.1038/s41589-026-02288-w

Yiyun Song

引用次数: 0

Scaling the protein universe 缩放蛋白质宇宙。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-20 DOI: 10.1038/s41589-026-02287-x

Gene Chong

引用次数: 0

Designed to bind 设计用于绑定。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-20 DOI: 10.1038/s41589-026-02286-y

Francesco Zamberlan

引用次数: 0

Restoring intracellular homeostasis disrupted by synthetic nanoassemblies 修复被合成纳米组件破坏的细胞内稳态

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-17 DOI: 10.1038/s41589-026-02279-x

Jiaqi Xing, Xiaoran Zheng, Yong Ren, Maximilian Schuler, David Y. W. Ng, Tanja Weil, Seraphine V. Wegner, Christopher V. Synatschke

{"title":"Restoring intracellular homeostasis disrupted by synthetic nanoassemblies","authors":"Jiaqi Xing, Xiaoran Zheng, Yong Ren, Maximilian Schuler, David Y. W. Ng, Tanja Weil, Seraphine V. Wegner, Christopher V. Synatschke","doi":"10.1038/s41589-026-02279-x","DOIUrl":"10.1038/s41589-026-02279-x","url":null,"abstract":"Cells have evolved to defend against perturbations by maintaining their intrinsic homeostasis to survive. However, no intrinsic pathway exists for them to expel new-to-biology synthetic nanostructures. Here we establish crosstalk between supramolecular transformations and genetic responses, achieving programmable influx–efflux cycles of nanoassemblies in living bacterial cells to restore redox and energy homeostasis. Specifically, a model photosensitizer–peptide conjugate undergoes multiple redox cycles between methionine and methionine sulfoxide (MetO), resulting in reversible morphological transformations between nanofibers (NFs) and nanoparticles (NPs). Upon irradiation, the oxidized peptide NPs are internalized into bacteria. To counteract the perturbations caused by internalized NPs, engineered bacteria activate the expression of MetO reductases in response to photo-oxidative stress. The internalized NPs are intracellularly enzymatically reduced such that they are expelled as reduced NFs, setting the stage for subsequent cycles. The concept presented here paves the way for the interlinked network between dynamic supramolecular assemblies and cellular regulatory behaviors. Cells have evolved defense pathways to maintain homeostasis against external perturbations, but not against new-to-nature nanomaterials, which can irreversibly accumulate and induce cell stress. Now, programmable peptide nanoassemblies have been designed that can morphologically transform in influx–efflux cycles in response to restoring redox homeostasis in bacterial cells.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"22 10","pages":"1676-1684"},"PeriodicalIF":15.8,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41589-026-02279-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459695","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

Selective chemical reprogramming of tumor-associated macrophages 肿瘤相关巨噬细胞的选择性化学重编程。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-15 DOI: 10.1038/s41589-026-02285-z

引用次数: 0

Early maturation of host antimicrobial peptide defences is associated with host–pathogen coexistence 宿主抗菌肽防御的早期成熟与宿主-病原体共存有关。

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-15 DOI: 10.1038/s41589-026-02254-6

Phillip A. Jervis, Gonçalo M. Rosa, Kieran A. Bates, Kersti Karu, Aamina Murtza, Thomas Defuentes, David Firer, Sam Edwards, Kevin Hopkins, François Le Mauff, Christopher J. Michaels, Tresai Jordine-Morgan, Christina Nylander, Christopher Sergeant, Emily J. Skelly, Tam T. Bui, Donald Sheppard, Xavier A. Harrison, Johanna Rhodes, Benjamin Tapley, Jaime Bosch, Trenton W. J. Garner, Matthew C. Fisher, Alethea B. Tabor

{"title":"Early maturation of host antimicrobial peptide defences is associated with host–pathogen coexistence","authors":"Phillip A. Jervis, Gonçalo M. Rosa, Kieran A. Bates, Kersti Karu, Aamina Murtza, Thomas Defuentes, David Firer, Sam Edwards, Kevin Hopkins, François Le Mauff, Christopher J. Michaels, Tresai Jordine-Morgan, Christina Nylander, Christopher Sergeant, Emily J. Skelly, Tam T. Bui, Donald Sheppard, Xavier A. Harrison, Johanna Rhodes, Benjamin Tapley, Jaime Bosch, Trenton W. J. Garner, Matthew C. Fisher, Alethea B. Tabor","doi":"10.1038/s41589-026-02254-6","DOIUrl":"10.1038/s41589-026-02254-6","url":null,"abstract":"Epizootic outbreaks of invasive pathogens, such as the fungal pathogen Batrachochytrium dendrobatidis (Bd), are increasingly recognized as a global threat to biodiversity. However, not all susceptible host populations are equally impacted by these disease outbreaks. While some populations persist despite intense infections and high mortality rates, others can transition to enzootic coexistence with the pathogen. Here, we use comparative peptidomics to identify differences in antimicrobial peptide (AMP) maturation in Bd-susceptible common midwife toads (Alytes obstetricans) through metamorphosis. Here, we show that animals that metamorphose before AMP immune maturation display a low-diversity AMP phenotype deficient in anti-Bd AMPs. Where a high incidence of postmetamorphic animals occur with immature AMPs, populations are associated with epizootic disease dynamics. Conversely, populations associated with mature AMPs are stable following invasion of the pathogen. Our results show that even intrinsically susceptible amphibian species can possess the tools that allow populations to recover following a severe Bd epizootic. Host antimicrobial peptides (AMPs) are a frontline defense against infection. Now, it has been shown that maturation of AMP repertoires early in life can predict stable host coexistence with a highly invasive pathogen.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"22 11","pages":"1731-1740"},"PeriodicalIF":15.8,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41589-026-02254-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148441030","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

Proteoform-specific enrichment of phosphopeptide isomers by polymer-based synthetic receptors 基于聚合物的合成受体对磷酸化肽异构体的蛋白质形态特异性富集

IF 15.8 1区生物学

Nature chemical biology Pub Date : 2026-07-13 DOI: 10.1038/s41589-026-02274-2

Anıl İncel, Sudhirkumar Shinde, Ignacio Arribas Díez, Maria M. Stollenwerk, Jingjing Xu, Tina Ravnsborg, Magnus E. Jakobsson, Ole N. Jensen, Börje Sellergren

{"title":"Proteoform-specific enrichment of phosphopeptide isomers by polymer-based synthetic receptors","authors":"Anıl İncel, Sudhirkumar Shinde, Ignacio Arribas Díez, Maria M. Stollenwerk, Jingjing Xu, Tina Ravnsborg, Magnus E. Jakobsson, Ole N. Jensen, Börje Sellergren","doi":"10.1038/s41589-026-02274-2","DOIUrl":"10.1038/s41589-026-02274-2","url":null,"abstract":"Site-level resolution of protein phosphorylation remains a central challenge in decoding cellular signaling and conventional global phosphoproteomics is limited in its ability to detect low-abundance peptides and resolve positional isomers. Here we introduce sequence-selective synthetic receptors based on imprinted polymers for targeted enrichment of defined phosphopeptide motifs from complex cancer cell proteomes. By encoding local sequence context into the binding interface, these receptors enable selective capture of closely related phosphorylation sites with high specificity. Using the T cell kinase ZAP70 as a model, we resolve phosphorylation at adjacent tyrosine residues (pY492 and pY493) within a regulatory motif, overcoming a long-standing limitation in site discrimination. Integrated with liquid chromatography–mass spectrometry workflows, this enables sensitive detection of low-abundance and isomeric phosphopeptides that evade conventional enrichment strategies. More broadly, our findings establish molecular imprinting as a programmable chemical platform for site-resolved phosphoproteomics, opening new avenues to interrogate signaling networks with molecular precision. Resolution of protein phosphorylation at specific sites is challenging. Now, synthetic receptors have been developed that enable high-resolution enrichment of ultralow-abundance phosphopeptide positional isomers from complex human proteomes.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"22 10","pages":"1610-1616"},"PeriodicalIF":15.8,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148432117","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