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Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas 从假单胞菌中发现非典型 C16-三萜类化合物并进行生物合成
IF 8.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-26 DOI: 10.1016/j.chembiol.2024.09.002
Xu-Hua Mo, Qing-Yin Pu, Tilo Lübken, Gui-Hong Yu, Mert Malay, Paul M. D’Agostino, Tobias A.M. Gulder
{"title":"Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas","authors":"Xu-Hua Mo, Qing-Yin Pu, Tilo Lübken, Gui-Hong Yu, Mert Malay, Paul M. D’Agostino, Tobias A.M. Gulder","doi":"10.1016/j.chembiol.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.09.002","url":null,"abstract":"Biosynthesis of sodorifen with a unique C<sub>16</sub>-bicyclo[3.2.1]octene framework requires an <em>S</em>-adenosyl methionine-dependent methyltransferase SodC and terpene cyclase SodD. While bioinformatic analyses reveal a wide distribution of the <em>sodCD</em> genes organization in bacteria, their functional diversity remains largely unknown. Herein, two sodorifen-type gene clusters, <em>pcch</em> and <em>pcau</em>, from <em>Pseudomonas</em> sp. are heterologously expressed in <em>Escherichia coli</em>, leading to the discovery of two C<sub>16</sub> terpenoids. Enzymatic synthesis of these compounds is achieved using the two (SodCD-like) pathway-specific enzymes. Enzyme assays using different combinations of methyltransferases and terpene synthases across the <em>pcch</em>, <em>pcau</em>, and <em>sod</em> pathways reveal a unifying biosynthetic mechanism: all three SodC-like enzymes methylate farnesyl pyrophosphate (FPP) with subsequent cyclization to a common intermediate, pre-sodorifen pyrophosphate. Structural diversification of this joint precursor solely occurs by the subsequently acting individual terpene synthases. Our findings expand basic biosynthetic understanding and structural diversity of unusual C<sub>16</sub>-terpenoids.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321402","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
Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration 微生物衍生代谢物对神经退行性病变产生影响的机制
IF 8.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-25 DOI: 10.1016/j.chembiol.2024.08.014
Lara Kern, Ignacio Mastandrea, Anna Melekhova, Eran Elinav
{"title":"Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration","authors":"Lara Kern, Ignacio Mastandrea, Anna Melekhova, Eran Elinav","doi":"10.1016/j.chembiol.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.08.014","url":null,"abstract":"Recent developments in microbiome research suggest that the gut microbiome may remotely modulate central and peripheral neuronal processes, ranging from early brain development to age-related changes. Dysbiotic microbiome configurations have been increasingly associated with neurological disorders, such as neurodegeneration, but causal understanding of these associations remains limited. Most mechanisms explaining how the microbiome may induce such remote neuronal effects involve microbially modulated metabolites that influx into the ‘sterile’ host. Some metabolites are able to cross the blood-brain barrier (BBB) to reach the central nervous system, where they can impact a variety of cells and processes. Alternatively, metabolites may directly signal to peripheral nerves to act as neurotransmitters or exert modulatory functions, or impact immune responses, which, in turn, modulate neuronal function and associated disease propensity. Herein, we review the current knowledge highlighting microbiome-modulated metabolite impacts on neuronal disease, while discussing unknowns, controversies and prospects impacting this rapidly evolving research field.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":8.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317170","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
The next Nobel Prize in chemistry or in physiology or medicine 下一个诺贝尔化学奖、生理学奖或医学奖
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.013
{"title":"The next Nobel Prize in chemistry or in physiology or medicine","authors":"","doi":"10.1016/j.chembiol.2024.08.013","DOIUrl":"10.1016/j.chembiol.2024.08.013","url":null,"abstract":"<div><p>In early October, the Nobel Prizes will honor groundbreaking discoveries. After the anticipated recognition of Katalin Karikó and Drew Weissman in 2023 for the development of RNA modifications that enabled the SARS-CoV-2 mRNA vaccine, we eagerly consider the next topics to be awarded. In the September 30<sup>th</sup> anniversary special issue of <em>Cell Chemical Biology</em>, we ask researchers from a range of backgrounds, what topic do you think deserves the next Nobel Prize in chemistry or in physiology or medicine, and why?</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246001","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
The best of both worlds: Chemigenetic fluorescent sensors for biological imaging 两全其美：用于生物成像的化学基因荧光传感器
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.002
{"title":"The best of both worlds: Chemigenetic fluorescent sensors for biological imaging","authors":"","doi":"10.1016/j.chembiol.2024.08.002","DOIUrl":"10.1016/j.chembiol.2024.08.002","url":null,"abstract":"<div><p>Synthetic-based fluorescent chemosensors and protein-based fluorescent biosensors are two well-established classes of tools for visualizing and monitoring biological processes in living tissues. Chemigenetic sensors, created using a combination of both synthetic parts and protein parts, are an emerging class of tools that aims to combine the strengths, and overcome the drawbacks, of traditional chemosensors and biosensors. This review will survey the landscape of strategies used for fluorescent chemigenetic sensor design. These strategies include: attachment of synthetic elements to proteins using <em>in vitro</em> protein conjugation; attachment of synthetic elements to proteins using autonomous protein labeling; and translational incorporation of unnatural amino acids.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130815","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
Prephenate decarboxylase: An unexplored branchpoint to unusual natural products Prephenate decarboxylase：通向不寻常天然产物的一个尚未探索的分支点
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.06.015
{"title":"Prephenate decarboxylase: An unexplored branchpoint to unusual natural products","authors":"","doi":"10.1016/j.chembiol.2024.06.015","DOIUrl":"10.1016/j.chembiol.2024.06.015","url":null,"abstract":"<div><p>Prephenate decarboxylases are a small family of enzymes which initiate a specialized divergence from the shikimate pathway, where prephenate (<strong>2</strong>) is decarboxylated without aromatization. In addition to effecting a challenging chemical transformation, prephenate decarboxylases have been implicated in the production of rare specialized metabolites, sometimes directly constructing bioactive warheads. Many of the biosynthetic steps to natural products derived from prephenate decarboxylases remain elusive. Here, we review prephenate decarboxylase research thus far and highlight natural products that may be derived from biosynthetic pathways involving prephenate decarboxylases. We also highlight commonly encountered challenges in the structure elucidation of these natural products. Prephenate decarboxylases are a gateway into understudied biosynthetic pathways which present a high potential for the discovery of novel and bioactive natural products, as well as new biosynthetic enzymes.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141754353","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
The physiological and pathological roles of RNA modifications in T cells T 细胞中 RNA 修饰的生理和病理作用
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.06.003
{"title":"The physiological and pathological roles of RNA modifications in T cells","authors":"","doi":"10.1016/j.chembiol.2024.06.003","DOIUrl":"10.1016/j.chembiol.2024.06.003","url":null,"abstract":"<div><p><span><span>RNA molecules undergo dynamic chemical modifications in response to various external or cellular stimuli. Some of those modifications have been demonstrated to post-transcriptionally modulate the </span>RNA transcription, localization, stability, translation, and degradation, ultimately tuning the fate decisions and function of </span>mammalian cells, particularly T cells. As a crucial part of adaptive immunity, T cells play fundamental roles in defending against infections and tumor cells. Recent findings have illuminated the importance of RNA modifications in modulating T cell survival, proliferation, differentiation, and functional activities. Therefore, understanding the epi-transcriptomic control of T cell biology enables a potential avenue for manipulating T cell immunity. This review aims to elucidate the physiological and pathological roles of internal RNA modifications in T cell development, differentiation, and functionality drawn from current literature, with the goal of inspiring new insights for future investigations and providing novel prospects for T cell-based immunotherapy.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561685","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
RNA and condensates: Disease implications and therapeutic opportunities RNA 和凝结物：疾病影响和治疗机会
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.009
{"title":"RNA and condensates: Disease implications and therapeutic opportunities","authors":"","doi":"10.1016/j.chembiol.2024.08.009","DOIUrl":"10.1016/j.chembiol.2024.08.009","url":null,"abstract":"<div><p>Biomolecular condensates are dynamic membraneless organelles that compartmentalize proteins and RNA molecules to regulate key cellular processes. Diverse RNA species exert their effects on the cell by their roles in condensate formation and function. RNA abnormalities such as overexpression, modification, and mislocalization can lead to pathological condensate behaviors that drive various diseases, including cancer, neurological disorders, and infections. Here, we review RNA’s role in condensate biology, describe the mechanisms of RNA-induced condensate dysregulation, note the implications for disease pathogenesis, and discuss novel therapeutic strategies. Emerging approaches to targeting RNA within condensates, including small molecules and RNA-based therapies that leverage the unique properties of condensates, may revolutionize treatment for complex diseases.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003581/pdfft?md5=b0f6fb8d9ad651a69c2d0a3dc45b2d59&pid=1-s2.0-S2451945624003581-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246801","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
What is chemical biology? 什么是化学生物学？
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.011
{"title":"What is chemical biology?","authors":"","doi":"10.1016/j.chembiol.2024.08.011","DOIUrl":"10.1016/j.chembiol.2024.08.011","url":null,"abstract":"<div><p>Since its inception, the chemical biology field has undergone significant evolution, with its definition varying greatly based on individual perspectives. For the September 30<sup>th</sup> anniversary special issue of <em>Cell Chemical Biology</em>, we asked our readers from a range of backgrounds, what is chemical biology?</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246002","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
Ligand discovery by activity-based protein profiling 通过基于活性的蛋白质分析发现配体
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.006
{"title":"Ligand discovery by activity-based protein profiling","authors":"","doi":"10.1016/j.chembiol.2024.08.006","DOIUrl":"10.1016/j.chembiol.2024.08.006","url":null,"abstract":"<div><p>Genomic technologies have led to massive gains in our understanding of human gene function and disease relevance. Chemical biologists are a primary beneficiary of this information, which can guide the prioritization of proteins for chemical probe and drug development. The vast functional and structural diversity of disease-relevant proteins, however, presents challenges for conventional small molecule screening libraries and assay development that in turn raise questions about the broader “druggability” of the human proteome. Here, we posit that activity-based protein profiling (ABPP), by generating global maps of small molecule-protein interactions in native biological systems, is well positioned to address major obstacles in human biology-guided chemical probe and drug discovery. We will support this viewpoint with case studies highlighting a range of small molecule mechanisms illuminated by ABPP that include the disruption and stabilization of biomolecular (protein-protein/nucleic acid) interactions and underscore allostery as a rich source of chemical tools for historically “undruggable” protein classes.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246006","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
Reflections from advisory board members and associate editors 顾问委员会成员和副主编的思考
IF 6.6 1区 生物学
Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.015
{"title":"Reflections from advisory board members and associate editors","authors":"","doi":"10.1016/j.chembiol.2024.08.015","DOIUrl":"10.1016/j.chembiol.2024.08.015","url":null,"abstract":"<div><p>For the celebration of the 30<sup>th</sup> anniversary of <em>Cell Chemical Biology</em>, in the September special issue, we asked former and current advisory board members and former editors to reflect on the advancements in chemical biology, changes in the field, and their insights into <em>Cell Chemical Biology</em> (originally <em>Chemistry &amp; Biology</em>).</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003647/pdfft?md5=2f38124a3b76bef314cf59b1accd156a&pid=1-s2.0-S2451945624003647-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246004","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
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