Nature chemical biology最新文献

Functional targeting of membrane transporters and enzymes to peroxisomes 膜转运蛋白和酶对过氧化物酶体的功能靶向

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-16 DOI: 10.1038/s41589-025-01948-7

Ka-Hei Siu, Victoria Lee, John E. Dueber

引用次数: 0

A SAMBA for chemically induced proximity 用于化学诱导接近的SAMBA

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-13 DOI: 10.1038/s41589-025-01934-z

Yang Zhou, Xiaoding Ma, Haifeng Ye

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A widespread metabolic gene cluster family in metazoans 在后生动物中广泛存在的代谢基因簇家族

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-13 DOI: 10.1038/s41589-025-01927-y

Natalie E. Grayson, Paul D. Scesa, Malia L. Moore, Jean-Baptiste Ledoux, Jessica Gomez-Garrido, Tyler Alioto, Todd P. Michael, Immo Burkhardt, Eric W. Schmidt, Bradley S. Moore

{"title":"A widespread metabolic gene cluster family in metazoans","authors":"Natalie E. Grayson, Paul D. Scesa, Malia L. Moore, Jean-Baptiste Ledoux, Jessica Gomez-Garrido, Tyler Alioto, Todd P. Michael, Immo Burkhardt, Eric W. Schmidt, Bradley S. Moore","doi":"10.1038/s41589-025-01927-y","DOIUrl":"https://doi.org/10.1038/s41589-025-01927-y","url":null,"abstract":"Octocorals are metazoans that prolifically produce terpenoid natural products, rivaling the chemical diversity of plants and microbes. We recently established that these cnidarians uniformly express terpene cyclases and that their encoding genes often reside within putative biosynthetic gene clusters (BGCs). Here we report the discovery and characterization of a widespread gene cluster family for briarane diterpenoid biosynthesis. We sequence five genomes from evolutionarily distinct families of briarane-producing octocorals, revealing a conserved five-gene cluster. Expressing these genes in heterologous hosts, we reconstitute the biosynthesis of cembrene B γ-lactone, an established molecule that contains the lactone structural feature distinctive of briarane diterpenoids. The discovery of the genomic basis of briarane biosynthesis establishes that animals also use gene cluster families to produce specialized metabolites. Furthermore, the presence of BGCs in octocorals proves that the formation and maintenance of BGCs related to specialized metabolite biosynthesis is a more widespread phenomenon than previously realized.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"223 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278797","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

Repurposing salicylic acid as a versatile inducer of proximity 重新利用水杨酸作为一个多用途的接近诱导剂

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-13 DOI: 10.1038/s41589-025-01918-z

Tianlu Wang, Siyao Liu, Yuepeng Ke, Sher Ali, Rui Wang, Tingting Hong, Ziying Liu, Guolin Ma, Tien-Hung Lan, Fen Wang, Michael X. Zhu, Yun Huang, Yubin Zhou

{"title":"Repurposing salicylic acid as a versatile inducer of proximity","authors":"Tianlu Wang, Siyao Liu, Yuepeng Ke, Sher Ali, Rui Wang, Tingting Hong, Ziying Liu, Guolin Ma, Tien-Hung Lan, Fen Wang, Michael X. Zhu, Yun Huang, Yubin Zhou","doi":"10.1038/s41589-025-01918-z","DOIUrl":"https://doi.org/10.1038/s41589-025-01918-z","url":null,"abstract":"Chemically induced proximity (CIP) has remarkably advanced the development of molecular and cellular therapeutics. To maximize therapeutic potential, there is a pressing need to expand the repertoire of CIP systems of translational values, favoring chemical ligands that are cost-effective, structurally simple, biocompatible, reversible and have minimal side effects. Here, we present a salicylic acid (SA)-mediated binary association system (SAMBA), evolved from a tobacco SA receptor, that enables rapid protein–protein heterodimerization in response to SA or aspirin after hydrolysis. We demonstrate the broad applicability of SAMBA in various biological contexts, including SA-dependent reprogramming of a protein-based reaction–diffusion system, graded gating of calcium channels, inducible initiation of receptor tyrosine kinase-mediated signaling and gene expression, and tunable activation of chimeric antigen receptor T cells. Our work establishes SAMBA as a versatile chemogenetic platform that allows temporal control of biological processes and therapeutic cells both in vitro and in vivo.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"44 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278845","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

Polyvalent folate receptor-targeting chimeras for degradation of membrane proteins 靶向多价叶酸受体的膜蛋白降解嵌合体

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-13 DOI: 10.1038/s41589-025-01924-1

Dian Xiao, Jingwen Dong, Fei Xie, Xun Feng, Jianfeng Wang, Xin Xu, Borui Tang, Cuicui Sun, Yuting Wang, Wu Zhong, Hongbin Deng, Xinbo Zhou, Song Li

{"title":"Polyvalent folate receptor-targeting chimeras for degradation of membrane proteins","authors":"Dian Xiao, Jingwen Dong, Fei Xie, Xun Feng, Jianfeng Wang, Xin Xu, Borui Tang, Cuicui Sun, Yuting Wang, Wu Zhong, Hongbin Deng, Xinbo Zhou, Song Li","doi":"10.1038/s41589-025-01924-1","DOIUrl":"https://doi.org/10.1038/s41589-025-01924-1","url":null,"abstract":"Lysosome-targeting chimeras (LYTACs) represent a revolutionary targeted protein degradation technology. However, the advancement of LYTACs faces substantial challenges due to the limited diversity of lysosome-trafficking receptors. In this study, we identified folate receptor α (FRα) as a new class of lysosome-trafficking receptors capable of facilitating the degradation of membrane proteins. Leveraging a polyvalent crosslinking strategy, we developed FRα-targeting chimeras (FRTACs), including enhanced green fluorescent protein-targeting FR-Ctx and PD-L1-targeting FR-Atz. The optimized FRTACs demonstrated subnanomolar potency in eliminating cell-surface targets, with efficacy dependent on both FRα expression and lysosomal activity. Specifically, FR-Ctx inhibited cancer cell proliferation, while FR-Atz enhanced T cell-mediated cytotoxicity against tumor cells. FR-Atz exhibited robust PD-L1 degradation efficiency in vivo and elicited tumor-specific immune responses by reprogramming the tumor microenvironment from an immunosuppressive to an immunostimulatory state in both RM-1 and humanized B16F10 mouse models. These findings establish FRTACs as a promising platform for the design of tumor-targeting LYTACs.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"11 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144278796","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

Author Correction: PROTAR Vaccine 2.0 generates influenza vaccines by degrading multiple viral proteins 作者更正：PROTAR疫苗2.0通过降解多种病毒蛋白产生流感疫苗

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-12 DOI: 10.1038/s41589-025-01956-7

Chunhe Zhang, Jihuan Hou, Zhen Li, Quan Shen, Haiqing Bai, Li Chen, Jinying Shen, Ping Wang, Yinlei Su, Jing Li, Qisi Zhang, Chengyao Liu, Xuetong Xi, Fei Qi, Yuting Chen, Xin Xie, Adam Yongxin Ye, Xiaoheng Liu, Roberto Plebani, George Church, Longlong Si

引用次数: 0

Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production 工程可控改变丙二酰辅酶a水平以提高聚酮的产量

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-11 DOI: 10.1038/s41589-025-01911-6

Sarah H. Klass, Mia Wesselkamper, Aidan E. Cowan, Namil Lee, Nathan Lanclos, Seokjung Cheong, Zilong Wang, Yan Chen, Jennifer W. Gin, Christopher J. Petzold, Jay D. Keasling

{"title":"Engineering controllable alteration of malonyl-CoA levels to enhance polyketide production","authors":"Sarah H. Klass, Mia Wesselkamper, Aidan E. Cowan, Namil Lee, Nathan Lanclos, Seokjung Cheong, Zilong Wang, Yan Chen, Jennifer W. Gin, Christopher J. Petzold, Jay D. Keasling","doi":"10.1038/s41589-025-01911-6","DOIUrl":"https://doi.org/10.1038/s41589-025-01911-6","url":null,"abstract":"Heterologous expression of polyketide synthase (PKS) genes in Escherichia coli has enabled the production of various valuable natural and synthetic products. However, the limited availability of malonyl-CoA (M-CoA) in E. coli remains a substantial impediment to high-titer polyketide production. Here we address this limitation by disrupting the native M-CoA biosynthetic pathway and introducing an orthogonal pathway comprising a malonate transporter and M-CoA ligase, enabling efficient M-CoA biosynthesis under malonate supplementation. This approach substantially increases M-CoA levels, enhancing fatty acid and polyketide titers while reducing the promiscuous activity of PKSs toward undesired acyl-CoA substrates. Subsequent adaptive laboratory evolution of these strains provides insights into M-CoA regulation and identifies mutations that further boost M-CoA and polyketide production. This strategy improves E. coli as a host for polyketide biosynthesis and advances understanding of M-CoA metabolism in microbial systems.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"20 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260301","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

Author Correction: Nuclear ubiquitination permits Hippo–YAP signal for liver development and tumorigenesis 作者更正：核泛素化允许Hippo-YAP信号参与肝脏发育和肿瘤发生

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-10 DOI: 10.1038/s41589-025-01958-5

Jinsong Wei, Zhifa Cao, Qing Li, Xiaoyu Li, Qingzhe Wang, Yiming Zhang, Run Zhang, Xingru Wu, Quanhui Dai, Xinyang Li, Zhaocai Zhou, Fenyong Sun, Shi Jiao, Bing Zhao

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Targeted RNA acetylation via a dCas13-guided engineered acetyl-transferase 通过dcas13引导的工程乙酰转移酶靶向RNA乙酰化

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-10 DOI: 10.1038/s41589-025-01923-2

引用次数: 0

Phase separation instead of binding strength determines target specificities of MAGUKs 相分离而不是结合强度决定了maguk的靶特异性

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-06-10 DOI: 10.1038/s41589-025-01925-0

Yan Chen, Chenxue Ma, Zeyu Shen, Shiwen Chen, Shihan Zhu, Bowen Jia, Shangyu Dang, Mingjie Zhang

{"title":"Phase separation instead of binding strength determines target specificities of MAGUKs","authors":"Yan Chen, Chenxue Ma, Zeyu Shen, Shiwen Chen, Shihan Zhu, Bowen Jia, Shangyu Dang, Mingjie Zhang","doi":"10.1038/s41589-025-01925-0","DOIUrl":"https://doi.org/10.1038/s41589-025-01925-0","url":null,"abstract":"Homologous proteins often have distinct functions, even if they share overlapping binding targets. PSD-95 and MAGI-2, two membrane-associated guanylate kinase (MAGUK)-family scaffolds in neuronal synapses, exemplify this. With unknown mechanisms, the two MAGUKs are localized at distinct subsynaptic compartments with PSD-95 inside the postsynaptic density (PSD) and MAGI-2 outside. Here we demonstrate that MAGI-2 forms condensates through phase separation. When coexisting with PSD proteins, the MAGI-2 condensate can enrich the extrasynaptic N-cadherin–β-catenin adhesion complex and the MAGI-2 condensates are immiscible with the PSD-95 condensates. Surprisingly, phosphorylated SAPAP is selectively enriched in the PSD-95 condensate, even though it binds to MAGI-2 with a higher affinity. The specific localization of SAPAP is because of the higher network complexities of the PSD-95-containing condensate than the MAGI-2 condensate. Thus, phase-separation-mediated molecular condensate formation can generate a previously unrecognized mode of molecular interaction and subcellular localization specificities that do not occur in dilute solutions.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"24 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252123","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