Mostafa Hagar , Raymond J. Andersen , Katherine S. Ryan
{"title":"Prephenate decarboxylase: An unexplored branchpoint to unusual natural products","authors":"Mostafa Hagar , Raymond J. Andersen , Katherine S. Ryan","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":"31 9","pages":"Pages 1610-1626"},"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}
Albert A. Antolin, Yimon Aye, Liron Bar-Peled, Elena De Vita, Natavan Dudkina, Michael C. Jewett, Hannah Kiely-Collins, Ralph Mazitschek, Zhenrun Jerry Zhang
{"title":"What is chemical biology?","authors":"Albert A. Antolin, Yimon Aye, Liron Bar-Peled, Elena De Vita, Natavan Dudkina, Michael C. Jewett, Hannah Kiely-Collins, Ralph Mazitschek, Zhenrun Jerry Zhang","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":"31 9","pages":"Pages 1562-1565"},"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}
{"title":"Ligand discovery by activity-based protein profiling","authors":"Micah J. Niphakis , Benjamin F. Cravatt","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":"31 9","pages":"Pages 1636-1651"},"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}
Michelle Arkin, Sara Buhrlage, Ling-Ling Chen, Peng Chen, Jason Gestwicki, Chuan He, Gerald F. Joyce, Angela Koehler, Milka Kostic, Jun Liu, Jim Wells
{"title":"Reflections from advisory board members and associate editors","authors":"Michelle Arkin, Sara Buhrlage, Ling-Ling Chen, Peng Chen, Jason Gestwicki, Chuan He, Gerald F. Joyce, Angela Koehler, Milka Kostic, Jun Liu, Jim Wells","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 & Biology</em>).</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1557-1561"},"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}
Lisa M. Breckels , Charlotte Hutchings , Kishor D. Ingole , Suyeon Kim , Kathryn S. Lilley , Mehul V. Makwana , Kieran J.A. McCaskie , Eneko Villanueva
{"title":"Advances in spatial proteomics: Mapping proteome architecture from protein complexes to subcellular localizations","authors":"Lisa M. Breckels , Charlotte Hutchings , Kishor D. Ingole , Suyeon Kim , Kathryn S. Lilley , Mehul V. Makwana , Kieran J.A. McCaskie , Eneko Villanueva","doi":"10.1016/j.chembiol.2024.08.008","DOIUrl":"10.1016/j.chembiol.2024.08.008","url":null,"abstract":"<div><p>Proteins are responsible for most intracellular functions, which they perform as part of higher-order molecular complexes, located within defined subcellular niches. Localization is both dynamic and context specific and mislocalization underlies a multitude of diseases. It is thus vital to be able to measure the components of higher-order protein complexes and their subcellular location dynamically in order to fully understand cell biological processes. Here, we review the current range of highly complementary approaches that determine the subcellular organization of the proteome. We discuss the scale and resolution at which these approaches are best employed and the caveats that should be taken into consideration when applying them. We also look to the future and emerging technologies that are paving the way for a more comprehensive understanding of the functional roles of protein isoforms, which is essential for unraveling the complexities of cell biology and the development of disease treatments.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1665-1687"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S245194562400357X/pdfft?md5=d7d9545c4fe5c1529fc55f268dc36ff3&pid=1-s2.0-S245194562400357X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246008","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}
James A. Gregory , Christopher M. Hickey , Juan Chavez , Angela M. Cacace
{"title":"New therapies on the horizon: Targeted protein degradation in neuroscience","authors":"James A. Gregory , Christopher M. Hickey , Juan Chavez , Angela M. Cacace","doi":"10.1016/j.chembiol.2024.08.010","DOIUrl":"10.1016/j.chembiol.2024.08.010","url":null,"abstract":"<div><p>This minireview explores the burgeoning field of targeted protein degradation (TPD) and its promising applications in neuroscience and clinical development. TPD offers innovative strategies for modulating protein levels, presenting a paradigm shift in small-molecule drug discovery and therapeutic interventions. Importantly, small-molecule protein degraders specifically target and remove pathogenic proteins from central nervous system cells without the drug delivery challenges of genomic and antibody-based modalities. Here, we review recent advancements in TPD technologies, highlight proteolysis targeting chimera (PROTAC) protein degrader molecules with proximity-induced degradation event-driven and iterative pharmacology, provide applications in neuroscience research, and discuss the high potential for translation of TPD into clinical settings.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1688-1698"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003593/pdfft?md5=1f027e9528aca8082bec51fd76809e7f&pid=1-s2.0-S2451945624003593-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246007","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}
{"title":"Celebrating 30 years of chemical biology: A toast to multidisciplinarity","authors":"Mishtu Dey, Samantha Nelson","doi":"10.1016/j.chembiol.2024.08.016","DOIUrl":"10.1016/j.chembiol.2024.08.016","url":null,"abstract":"","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1555-1556"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246068","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}
{"title":"Insights into bacterial metabolism from small RNAs","authors":"Kai Papenfort , Gisela Storz","doi":"10.1016/j.chembiol.2024.07.002","DOIUrl":"10.1016/j.chembiol.2024.07.002","url":null,"abstract":"<div><p>The study of small, regulatory RNAs (sRNA) that act by base-pairing with target RNAs in bacteria has been steadily advancing, particularly with the availability of more and more transcriptome and RNA-RNA interactome datasets. While the characterization of multiple sRNAs has helped to elucidate their mechanisms of action, these studies also are providing insights into protein function, control of metabolic flux, and connections between metabolic pathways as we will discuss here. In describing several examples of the metabolic insights gained, we will summarize the different types of base-pairing sRNAs including mRNA-derived sRNAs, sponge RNAs, RNA mimics, and dual-function RNAs as well as suggest how information about sRNAs could be exploited in the future.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1571-1577"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877645","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}
{"title":"Meet the authors: Lydia P. Tsamouri and Daniel A. Bachovchin","authors":"Lydia P. Tsamouri, Daniel A. Bachovchin","doi":"10.1016/j.chembiol.2024.08.012","DOIUrl":"10.1016/j.chembiol.2024.08.012","url":null,"abstract":"<div><p>In an interview with Dr. Mishtu Dey, editor-in-chief of <em>Cell Chemical Biology</em>, the authors of the article entitled “The hydrophobicity of the CARD8 N-terminus tunes inflammasome activation” share their perspectives on the ways chemical biology enriches immunology research, the challenges and opportunities in the field, and their scientific career paths.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1568-1570"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003611/pdfft?md5=399618023e792f8827f726e2f978ec23&pid=1-s2.0-S2451945624003611-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246003","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}
{"title":"Membrane remodeling via ubiquitin-mediated pathways","authors":"Anne-Claire Jacomin , Ivan Dikic","doi":"10.1016/j.chembiol.2024.08.007","DOIUrl":"10.1016/j.chembiol.2024.08.007","url":null,"abstract":"<div><p>The dynamic process of membrane shaping and remodeling plays a vital role in cellular functions, with proteins and cellular membranes interacting intricately to adapt to various cellular needs and environmental cues. Ubiquitination—a posttranslational modification—was shown to be essential in regulating membrane structure and shape. It influences virtually all pathways relying on cellular membranes, such as endocytosis and autophagy by directing protein degradation, sorting, and oligomerization. Ubiquitin is mostly known as a protein modifier; however, it was reported that ubiquitin and ubiquitin-like proteins can associate directly with lipids, affecting membrane curvature and dynamics. In this review, we summarize some of the current knowledge on ubiquitin-mediated membrane remodeling in the context of endocytosis, autophagy, and ER-phagy.</p></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 9","pages":"Pages 1627-1635"},"PeriodicalIF":6.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2451945624003568/pdfft?md5=ece0af39be652dce7a41d4b687f8ec63&pid=1-s2.0-S2451945624003568-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142246005","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}