Nature chemical biology最新文献_第4页

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-16 DOI: 10.1038/s41589-024-01707-0

Xiao-Wang Chen, Zhiyu Bo, Yang Yang

引用次数: 0

Engineered IscB–ωRNA system with expanded target range for base editing 工程化 IscB-ωRNA 系统扩大了碱基编辑的目标范围

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-15 DOI: 10.1038/s41589-024-01706-1

Qingquan Xiao, Guoling Li, Dingyi Han, Haoqiang Wang, Mingyu Yao, Tingting Ma, Jingxing Zhou, Yu Zhang, Xiumei Zhang, Bingbing He, Yuan Yuan, Linyu Shi, Tong Li, Hui Yang, Jinhai Huang, Hainan Zhang

{"title":"Engineered IscB–ωRNA system with expanded target range for base editing","authors":"Qingquan Xiao, Guoling Li, Dingyi Han, Haoqiang Wang, Mingyu Yao, Tingting Ma, Jingxing Zhou, Yu Zhang, Xiumei Zhang, Bingbing He, Yuan Yuan, Linyu Shi, Tong Li, Hui Yang, Jinhai Huang, Hainan Zhang","doi":"10.1038/s41589-024-01706-1","DOIUrl":"https://doi.org/10.1038/s41589-024-01706-1","url":null,"abstract":"As the evolutionary ancestor of Cas9 nuclease, IscB proteins serve as compact RNA-guided DNA endonucleases and nickases, making them strong candidates for base editing. Nevertheless, the narrow targeting scope limits the application of IscB systems; thus, it is necessary to find more IscBs that recognize different target-adjacent motifs (TAMs). Here, we identified 10 of 19 uncharacterized IscB proteins from uncultured microbes with activity in mammalian cells. Through protein and ωRNA engineering, we further enhanced the activity of IscB ortholog IscB.m16 and expanded its TAM scope from MRNRAA to NNNGNA, resulting in a variant named IscB.m16*. By fusing the deaminase domains with IscB.m16* nickase, we generated IscB.m16*-derived base editors that exhibited robust base-editing efficiency in mammalian cells and effectively restored Duchenne muscular dystrophy proteins in diseased mice through single adeno-associated virus delivery. Thus, this study establishes a set of compact base-editing tools for basic research and therapeutic applications.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141986326","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

Eating a way out of antibiotics 吃出抗生素

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01698-y

Felix Wong

引用次数: 0

Shifting redox reaction equilibria on demand using an orthogonal redox cofactor 利用正交氧化还原辅助因子按需改变氧化还原反应平衡

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01702-5

Derek Aspacio, Yulai Zhang, Youtian Cui, Emma Luu, Edward King, William B. Black, Sean Perea, Qiang Zhu, Yongxian Wu, Ray Luo, Justin B. Siegel, Han Li

{"title":"Shifting redox reaction equilibria on demand using an orthogonal redox cofactor","authors":"Derek Aspacio, Yulai Zhang, Youtian Cui, Emma Luu, Edward King, William B. Black, Sean Perea, Qiang Zhu, Yongxian Wu, Ray Luo, Justin B. Siegel, Han Li","doi":"10.1038/s41589-024-01702-5","DOIUrl":"https://doi.org/10.1038/s41589-024-01702-5","url":null,"abstract":"Nature’s two redox cofactors, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+), are held at different reduction potentials, driving catabolism and anabolism in opposite directions. In biomanufacturing, there is a need to flexibly control redox reaction direction decoupled from catabolism and anabolism. We established nicotinamide mononucleotide (NMN+) as a noncanonical cofactor orthogonal to NAD(P)+. Here we present the development of Nox Ortho, a reduced NMN+ (NMNH)-specific oxidase, that completes the toolkit to modulate NMNH:NMN+ ratio together with an NMN+-specific glucose dehydrogenase (GDH Ortho). The design principle discovered from Nox Ortho engineering and modeling is facilely translated onto six different enzymes to create NMN(H)-orthogonal biocatalysts with a consistent ~103–106-fold cofactor specificity switch from NAD(P)+ to NMN+. We assemble these enzymes to produce stereo-pure 2,3-butanediol in cell-free systems and in Escherichia coli, enabled by NMN(H)’s distinct redox ratio firmly set by its designated driving forces, decoupled from both NAD(H) and NADP(H).<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974158","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

One-carbon footprint in B cells B 细胞中的单碳足迹

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01703-4

Rebekah Steiner, Julia Jellusova

引用次数: 0

Persistent glucose consumption under antibiotic treatment protects bacterial community 抗生素治疗下的持续葡萄糖消耗保护细菌群落

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2024-08-13 DOI: 10.1038/s41589-024-01708-z

Yuzhen Zhang, Yumin Cai, Xin Jin, Qile Wu, Fan Bai, Jintao Liu

{"title":"Persistent glucose consumption under antibiotic treatment protects bacterial community","authors":"Yuzhen Zhang, Yumin Cai, Xin Jin, Qile Wu, Fan Bai, Jintao Liu","doi":"10.1038/s41589-024-01708-z","DOIUrl":"https://doi.org/10.1038/s41589-024-01708-z","url":null,"abstract":"Antibiotics typically induce major physiological changes in bacteria. However, their effect on nutrient consumption remains unclear. Here we found that Escherichia coli communities can sustain normal levels of glucose consumption under a broad range of antibiotics. The community-living resulted in a low membrane potential in the bacteria, allowing slow antibiotic accumulation on treatment and better adaptation. Through multi-omics analysis, we identified a prevalent adaptive response characterized by the upregulation of lipid synthesis, which substantially contributes to sustained glucose consumption. The consumption was maintained by the periphery region of the community, thereby restricting glucose penetration into the community interior. The resulting spatial heterogeneity in glucose availability protected the interior from antibiotic accumulation in a membrane potential-dependent manner, ensuring rapid recovery of the community postantibiotic treatment. Our findings unveiled a community-level antibiotic response through spatial regulation of metabolism and suggested new strategies for antibiotic therapies.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":14.8,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141974160","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

Single-cell sensor analyses reveal signaling programs enabling Ras-G12C drug resistance. 单细胞传感器分析揭示了促成 Ras-G12C 耐药性的信号传导程序。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-05 DOI: 10.1038/s41589-024-01684-4

Jason Z Zhang, Shao-En Ong, David Baker, Dustin J Maly

引用次数: 0

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2. 一种天然小分子通过靶向载脂蛋白 L2 缓解肝纤维化。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-05 DOI: 10.1038/s41589-024-01704-3

Lu Gan, Qiwei Jiang, Dong Huang, Xueji Wu, Xinying Zhu, Lei Wang, Wei Xie, Jialuo Huang, Runzhu Fan, Yihang Jing, Guihua Tang, Xiang David Li, Jianping Guo, Sheng Yin

{"title":"A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.","authors":"Lu Gan, Qiwei Jiang, Dong Huang, Xueji Wu, Xinying Zhu, Lei Wang, Wei Xie, Jialuo Huang, Runzhu Fan, Yihang Jing, Guihua Tang, Xiang David Li, Jianping Guo, Sheng Yin","doi":"10.1038/s41589-024-01704-3","DOIUrl":"https://doi.org/10.1038/s41589-024-01704-3","url":null,"abstract":"Liver fibrosis is an urgent clinical problem without effective therapies. Here we conducted a high-content screening on a natural Euphorbiaceae diterpenoid library to identify a potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP). Leveraging a photo-affinity labeling approach, apolipoprotein L2 (APOL2), an endoplasmic reticulum (ER)-rich protein, was identified as the direct target of DP. Mechanistically, APOL2 is induced in activated hepatic stellate cells upon transforming growth factor-β1 (TGF-β1) stimulation, which then binds to sarcoplasmic/ER calcium ATPase 2 (SERCA2) to trigger ER stress and elevate its downstream protein kinase R-like ER kinase (PERK)-hairy and enhancer of split 1 (HES1) axis, ultimately promoting liver fibrosis. As a result, targeting APOL2 by DP or ablation of APOL2 significantly impairs APOL2-SERCA2-PERK-HES1 signaling and mitigates fibrosis progression. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis but also highlight DP as a promising lead for treatment of this symptom.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":12.9,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893845","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

Nanometer-resolution tracking of single cargo reveals dynein motor mechanisms. 对单个货物的纳米分辨率追踪揭示了动力蛋白的运动机制。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-01 DOI: 10.1038/s41589-024-01694-2

Chunte Sam Peng, Yunxiang Zhang, Qian Liu, G Edward Marti, Yu-Wen Alvin Huang, Thomas C Südhof, Bianxiao Cui, Steven Chu

引用次数: 0

Photoproximity labeling of endogenous receptors in the live mouse brain in minutes. 在几分钟内对活体小鼠大脑中的内源性受体进行光接近标记。

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2024-08-01 DOI: 10.1038/s41589-024-01692-4

Mikiko Takato, Seiji Sakamoto, Hiroshi Nonaka, Fátima Yuri Tanimura Valor, Tomonori Tamura, Itaru Hamachi

{"title":"Photoproximity labeling of endogenous receptors in the live mouse brain in minutes.","authors":"Mikiko Takato, Seiji Sakamoto, Hiroshi Nonaka, Fátima Yuri Tanimura Valor, Tomonori Tamura, Itaru Hamachi","doi":"10.1038/s41589-024-01692-4","DOIUrl":"https://doi.org/10.1038/s41589-024-01692-4","url":null,"abstract":"Understanding how protein-protein interaction networks in the brain give rise to cognitive functions necessitates their characterization in live animals. However, tools available for this purpose require potentially disruptive genetic modifications and lack the temporal resolution necessary to track rapid changes in vivo. Here we leverage affinity-based targeting and photocatalyzed singlet oxygen generation to identify neurotransmitter receptor-proximal proteins in the live mouse brain using only small-molecule reagents and minutes of photoirradiation. Our photooxidation-driven proximity labeling for proteome identification (named PhoxID) method not only recapitulated the known interactomes of three endogenous neurotransmitter receptors (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), inhibitory γ-aminobutyric acid type A receptor and ionotropic glutamate receptor delta-2) but also uncovered age-dependent shifts, identifying NECTIN3 and IGSF3 as developmentally regulated AMPAR-proximal proteins in the cerebellum. Overall, this work establishes a flexible and generalizable platform to study receptor microenvironments in genetically intact specimens with an unprecedented temporal resolution.","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":null,"pages":null},"PeriodicalIF":12.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141875357","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