Nature chemical biology最新文献_第8页

De novo biosynthesis of plant lignans by synthetic yeast consortia 合成酵母菌群对植物木脂素的重新生物合成

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-17 DOI: 10.1038/s41589-025-01861-z

Ruibing Chen, Xianghui Chen, Yu Chen, Jindong Yang, Wansheng Chen, Yongjin J. Zhou, Lei Zhang

{"title":"De novo biosynthesis of plant lignans by synthetic yeast consortia","authors":"Ruibing Chen, Xianghui Chen, Yu Chen, Jindong Yang, Wansheng Chen, Yongjin J. Zhou, Lei Zhang","doi":"10.1038/s41589-025-01861-z","DOIUrl":"https://doi.org/10.1038/s41589-025-01861-z","url":null,"abstract":"Reconstructing the biosynthesis of complex natural products such as lignans in yeast is challenging and can result in metabolic promiscuity, affecting the biosynthetic efficiency. Here we divide the lignan biosynthetic pathway across a synthetic yeast consortium with obligated mutualism and use ferulic acid as a metabolic bridge. This cooperative system successfully overcomes the metabolic promiscuity and synthesizes the common precursor, coniferyl alcohol. Furthermore, combined with systematic engineering strategies, we achieve the de novo synthesis of key lignan skeletons, pinoresinol and lariciresinol, and verify the scalability of the consortium by synthesizing complex lignans, including antiviral lariciresinol diglucoside. These results provide a starting engineering platform for the heterologous synthesis of lignans. In particular, the study illustrates that the yeast consortium with obligate mutualism is a promising strategy that mimics the metabolic division of labor among multiple plant cells, thereby improving the biosynthesis of long pathways and complex natural products.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"16 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635298","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: A cell-free biosensor signal amplification circuit with polymerase strand recycling 作者更正：无细胞生物传感器信号放大电路与聚合酶链回收

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-17 DOI: 10.1038/s41589-025-01884-6

Yueyi Li, Tyler Lucci, Matias Villarruel Dujovne, Jaeyoung Kirsten Jung, Daiana A. Capdevila, Julius B. Lucks

引用次数: 0

Post-translational modifications orchestrate the intrinsic signaling bias of GPR52 翻译后修饰协调了GPR52固有的信号偏倚

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-14 DOI: 10.1038/s41589-025-01864-w

Bingjie Zhang, Wei Ge, Mengna Ma, Shanshan Li, Jie Yu, Guang Yang, Huilan Wang, Jingwen Li, Qingrun Li, Rong Zeng, Boxun Lu, Wenqing Shui

{"title":"Post-translational modifications orchestrate the intrinsic signaling bias of GPR52","authors":"Bingjie Zhang, Wei Ge, Mengna Ma, Shanshan Li, Jie Yu, Guang Yang, Huilan Wang, Jingwen Li, Qingrun Li, Rong Zeng, Boxun Lu, Wenqing Shui","doi":"10.1038/s41589-025-01864-w","DOIUrl":"https://doi.org/10.1038/s41589-025-01864-w","url":null,"abstract":"Despite recent advances in G-protein-coupled receptor (GPCR) biology, the regulation of GPCR activation, signaling and function by post-translational modifications (PTMs) remains largely unexplored. In this study of GPR52, an orphan GPCR with exceedingly high constitutive G-protein activity that is emerging as a neurotherapeutic target, we discovered its disproportionately low arrestin recruitment activity. After profiling the N-glycosylation and phosphorylation patterns, we found that these two types of PTMs differentially shape the intrinsic signaling bias of GPR52. While N-terminal N-glycosylation promotes constitutive Gs signaling possibly through favoring the self-activating conformation, phosphorylation in helix 8, to our great surprise, suppresses arrestin recruitment and attenuates receptor internalization. In addition, we uncovered the counteracting roles of N-glycosylation and phosphorylation in modulating GPR52-dependent accumulation of the huntingtin protein in brain striatal cells. Our study provides new insights into the regulation of intrinsic signaling bias and cellular function of an orphan GPCR through distinct PTMs in different motifs.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"23 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618341","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

Programmable solid-state condensates for spatiotemporal control of mammalian gene expression 可编程固态冷凝物用于哺乳动物基因表达的时空控制

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-14 DOI: 10.1038/s41589-025-01860-0

Yukai Wang, Jian Jiang, Qiqi Xiong, Shichao Li, Jiawei Shao, Mingqi Xie, An-Ping Zeng

{"title":"Programmable solid-state condensates for spatiotemporal control of mammalian gene expression","authors":"Yukai Wang, Jian Jiang, Qiqi Xiong, Shichao Li, Jiawei Shao, Mingqi Xie, An-Ping Zeng","doi":"10.1038/s41589-025-01860-0","DOIUrl":"https://doi.org/10.1038/s41589-025-01860-0","url":null,"abstract":"Engineering of nuclear condensates with chemically inducible gene switches is highly desired but challenging for precise and on-demand regulation of mammalian gene expression. Here, we harness the phase-separation capability of biomolecular condensates and describe a versatile strategy to chemically program ligand-dependent gene expression at various stages of interest. By engineering synthetic anchor proteins capable of tethering various genetically encoded condensate structures toward different cellular compartments or gene products of interest, inducible regulation of transcriptional and translational activities was achieved at different endogenous and episomal loci using the same sets of anchor proteins and synthetic solid-state condensates. Using such a holistic condensate-based strategy, we not only achieved regulation performances comparing favorably to state-of-the-art strategies described for CRISPR–Cas9 activity and transcriptional silencing but further showed that chemically inducible retention of mRNA molecules into engineered condensate structures within the nucleus can become a remarkably efficient alternative for translational regulation.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"88 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618342","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

Molecular basis of β-arrestin coupling to the metabotropic glutamate receptor mGlu3 β-阻滞蛋白偶联代谢促谷氨酸受体mGlu3的分子基础

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-06 DOI: 10.1038/s41589-025-01858-8

Tianlei Wen, Mei Du, Yue Lu, Nan Jia, Xuhang Lu, Ning Liu, Shenghai Chang, Xing Zhang, Yuequan Shen, Xue Yang

{"title":"Molecular basis of β-arrestin coupling to the metabotropic glutamate receptor mGlu3","authors":"Tianlei Wen, Mei Du, Yue Lu, Nan Jia, Xuhang Lu, Ning Liu, Shenghai Chang, Xing Zhang, Yuequan Shen, Xue Yang","doi":"10.1038/s41589-025-01858-8","DOIUrl":"https://doi.org/10.1038/s41589-025-01858-8","url":null,"abstract":"β-Arrestins (βarrs) mediate the desensitization and internalization of activated G-protein-coupled receptors (GPCRs). The molecular mechanism by which dimeric family C GPCR members recruit arrestins remains elusive. Here we report two structures of metabotropic glutamate receptor subtype 3 (mGlu3) coupled to βarr1, with stoichiometries of 2:1 and 2:2. The l-glutamate-bound mGlu3 dimer adopts an inactive state, with both Venus flytrap domains closed, engaging βarr1 either asymmetrically or symmetrically. The transmembrane domain of the mGlu3 protomer interacts with βarr1 through a binding pocket formed by three intracellular loops and an ordered C-terminal region. Three phosphorylation sites (pS857, pS859 and pT860) on the C-terminal tail of mGlu3 engage the N domain of βarr1. βarr1 stabilizes mGlu3 in an inactive conformation, characterized by a TM3/TM4–TM3/TM4 dimeric interface, previously observed in the negative allosteric modulator-bound structure of mGlu3. Our findings provide important insights into βarr-mediated inactivation of family C GPCRs.<figure></figure>","PeriodicalId":18832,"journal":{"name":"Nature chemical biology","volume":"18 1","pages":""},"PeriodicalIF":14.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560766","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

RAS signaling gets granular RAS信号变得精细

IF 14.8 1区生物学

Nature chemical biology Pub Date : 2025-03-04 DOI: 10.1038/s41589-025-01851-1

Hugo Lavoie, Marc Therrien

引用次数: 0

The last piece in fucosylation 聚焦化的最后一部分

IF 12.9 1区生物学

Nature chemical biology Pub Date : 2025-03-03 DOI: 10.1038/s41589-025-01850-2

Yasuhiko Kizuka

引用次数: 0

Publisher Correction: Visualizing drug effects over time in live animals using optical pharmacodynamics 出版者更正：使用光学药效学在活体动物中观察药物随时间的作用