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Accessing and exploring the unusual chemistry by radical SAM-RiPP enzymes 通过自由基 SAM-RiPP 酶获取和探索不寻常的化学性质。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-24 DOI: 10.1016/j.cbpa.2024.102483
Qianqian Guo, Brandon I. Morinaka
{"title":"Accessing and exploring the unusual chemistry by radical SAM-RiPP enzymes","authors":"Qianqian Guo,&nbsp;Brandon I. Morinaka","doi":"10.1016/j.cbpa.2024.102483","DOIUrl":"10.1016/j.cbpa.2024.102483","url":null,"abstract":"<div><p>Radical SAM enzymes involved in the biosynthesis of ribosomally synthesized and post-translationally modified peptides catalyze unusual transformations that lead to unique peptide scaffolds and building blocks. Several natural products from these pathways show encouraging antimicrobial activities and represent next-generation therapeutics for infectious diseases. These systems are uniquely configured to benefit from genome-mining approaches because minimal substrate and cognate modifying enzyme expression can reveal unique, chemically complex transformations that outperform late-stage chemical reactions. This report highlights the main strategies used to reveal these enzymatic transformations, which have relied mainly on genome mining using enzyme-first approaches. We describe the general biosynthetic components for rSAM enzymes and highlight emerging approaches that may broaden the discovery and study of rSAM-RiPP enzymes. The large number of uncharacterized rSAM proteins, coupled with their unpredictable transformations, will continue to be an essential and exciting resource for enzyme discovery.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102483"},"PeriodicalIF":6.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Genome mining for new enediyne antibiotics 基因组挖掘新的烯啶抗生素。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-24 DOI: 10.1016/j.cbpa.2024.102481
Esther J. Han , Mohammad R. Seyedsayamdost
{"title":"Genome mining for new enediyne antibiotics","authors":"Esther J. Han ,&nbsp;Mohammad R. Seyedsayamdost","doi":"10.1016/j.cbpa.2024.102481","DOIUrl":"10.1016/j.cbpa.2024.102481","url":null,"abstract":"<div><p>Enediyne antibiotics epitomize nature's chemical creativity. They contain intricate molecular architectures that are coupled with potent biological activities involving double-stranded DNA scission. The recent explosion in microbial genome sequences has revealed a large reservoir of novel enediynes. However, while hundreds of enediyne biosynthetic gene clusters (BGCs) can be detected, less than two dozen natural products have been characterized to date as many clusters remain silent or sparingly expressed under standard laboratory growth conditions. This review focuses on four distinct strategies, which have recently enabled discoveries of novel enediynes: phenotypic screening from rare sources, biosynthetic manipulation, genomic signature-based PCR screening, and DNA-cleavage assays coupled with activation of silent BGCs via high-throughput elicitor screening. With an abundance of enediyne BGCs and emerging approaches for accessing them, new enediyne natural products and further insights into their biogenesis are imminent.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102481"},"PeriodicalIF":6.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Reactions of lipid hydroperoxides and how they may contribute to ferroptosis sensitivity 脂质氢过氧化物的反应及其对铁中毒敏感性的影响
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-21 DOI: 10.1016/j.cbpa.2024.102478
Dmitry D. Saraev, Derek A. Pratt
{"title":"Reactions of lipid hydroperoxides and how they may contribute to ferroptosis sensitivity","authors":"Dmitry D. Saraev,&nbsp;Derek A. Pratt","doi":"10.1016/j.cbpa.2024.102478","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102478","url":null,"abstract":"<div><p>The accumulation of lipid hydroperoxides (LOOHs) has long been associated with numerous pathologies and has more recently been shown to drive a specific type of cell death known as ferroptosis. In competition with their detoxification by glutathione peroxidases, LOOHs can react with both one-electron reductants and one-electron oxidants to afford radicals that initiate lipid peroxidation (LPO) chain reactions leading to more LOOH. These radicals can alternatively undergo a variety of (primarily unimolecular) reactions leading to electrophilic species that destabilize the membrane and/or react with cellular nucleophiles. While some reaction mechanisms leading to lipid-derived electrophiles have been known for some time, others have only recently been elucidated. Since LOOH (and related peroxides, LOOL) undergo these various reactions at different rates to afford distinct product distributions specific to their structures, not all LOOHs (and LOOLs) should be equivalently problematic for the cell – be it in their propensity to initiate further LPO or fragment to electrophiles, drive membrane permeabilization and eventual cell death. Herein we briefly review the fates of LOOH and discuss how they may contribute to the modulation of cell sensitivity to ferroptosis by different lipids.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102478"},"PeriodicalIF":6.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000541/pdfft?md5=ce43e60434833511550b3e2a240cf1ab&pid=1-s2.0-S1367593124000541-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141438050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Finding ways into the cytosol: Peptide-mediated approaches for delivering proteins into cells 寻找进入细胞质的途径：以肽为媒介将蛋白质送入细胞的方法
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.cbpa.2024.102482
Yoshimasa Kawaguchi, Shiroh Futaki
{"title":"Finding ways into the cytosol: Peptide-mediated approaches for delivering proteins into cells","authors":"Yoshimasa Kawaguchi,&nbsp;Shiroh Futaki","doi":"10.1016/j.cbpa.2024.102482","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102482","url":null,"abstract":"<div><p>The delivery of functional proteins, including antibodies, into cells opens up many opportunities to regulate cellular events, with significant implications for studies in chemical biology and therapeutics. The inside of cells is isolated from the outside by the cell membrane. The hydrophilic nature of proteins prevents direct permeation of proteins through the cell membrane by passive diffusion. Therefore, delivery routes using endocytic uptake followed by endosomal escape have been explored. Alternatively, delivery concepts using transient permeabilization of cell membranes or effective promotion of endocytic uptake and endosomal escape using modified membrane-lytic peptides have been reported in recent years. Non-canonical protein delivery concepts, such as the use of liquid droplets or coacervates, have also been proposed. This review highlights some of the topics in peptide-mediated intracellular protein delivery.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102482"},"PeriodicalIF":6.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Recent applications of fluorescence correlation spectroscopy in live cells 荧光相关光谱在活细胞中的最新应用
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-20 DOI: 10.1016/j.cbpa.2024.102480
Adam W. Smith
{"title":"Recent applications of fluorescence correlation spectroscopy in live cells","authors":"Adam W. Smith","doi":"10.1016/j.cbpa.2024.102480","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102480","url":null,"abstract":"<div><p>As a time-domain analogue of fluorescence imaging, FCS offers valuable insights into molecular dynamics, interactions, and concentrations within living cells. The primary insight generated by FCS is molecular mobility and concentration, which makes it useful for investigating molecular-scale details without the need for enrichment or separation. A specific strength of FCS is the ability to probe protein–protein interactions in live cells and several recent applications in this area are summarized. FCS is also used to investigate plasma membrane protein organization, with many applications to cell surface receptors and the mechanisms of drug binding. Finally, FCS is undergoing continual methodological innovations, such as imaging FCS, SPIM-FCS PIE-FCCS, STED-FCS, three-color FCS, and massively parallel FCS, which extend the capabilities to investigate molecular dynamics at different spatial and temporal scales. These innovations enable detailed examinations of cellular processes, including cellular transport and the spatial organization of membrane proteins.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102480"},"PeriodicalIF":6.9,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141434922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 nanotechnology on the horizon: Self-assembly, chemical modifications, and functional applications 地平线上的 RNA 纳米技术：自组装、化学修饰和功能应用。
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-17 DOI: 10.1016/j.cbpa.2024.102479
Jaimie Marie Stewart
{"title":"RNA nanotechnology on the horizon: Self-assembly, chemical modifications, and functional applications","authors":"Jaimie Marie Stewart","doi":"10.1016/j.cbpa.2024.102479","DOIUrl":"10.1016/j.cbpa.2024.102479","url":null,"abstract":"<div><p>RNA nanotechnology harnesses the unique chemical and structural properties of RNA to build nanoassemblies and supramolecular structures with dynamic and functional capabilities. This review focuses on design and assembly approaches to building RNA structures, the RNA chemical modifications used to enhance stability and functionality, and modern-day applications in therapeutics, biosensing, and bioimaging.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102479"},"PeriodicalIF":7.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000553/pdfft?md5=1a781e0068b6a195e0e0cc742548b945&pid=1-s2.0-S1367593124000553-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141417055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Recent advances in engineering microorganisms for the production of natural food colorants 利用微生物工程技术生产天然食用色素的最新进展
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-14 DOI: 10.1016/j.cbpa.2024.102477
Philip Tinggaard Thomsen, Susanne Roenfeldt Nielsen, Irina Borodina
{"title":"Recent advances in engineering microorganisms for the production of natural food colorants","authors":"Philip Tinggaard Thomsen,&nbsp;Susanne Roenfeldt Nielsen,&nbsp;Irina Borodina","doi":"10.1016/j.cbpa.2024.102477","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102477","url":null,"abstract":"<div><p>Food colorants are frequently added to processed foods since color is an important tool in the marketing of food products, influencing consumer perceptions, preferences, and purchasing behavior. While synthetic dyes currently dominate the food colorant market, consumer concern regarding their safety and sustainability is driving a demand for their replacement with naturally derived alternatives. However, natural colorants are costly compared to their synthetic counterparts as the pigment content in the native sources is usually very low and extraction can be challenging. Recent advances in the engineering of microbial metabolism have sparked interest in the development of cell factories capable of producing natural colorants from renewable resources. This review summarizes major developments within metabolic engineering for the production of nature-identical food colorants by fermentation. Additionally, it highlights common applications, formulations, and physicochemical characteristics of prevalent pigment classes. Lastly, it outlines a workflow for accelerating the optimization of cell factories for the production or derivatization of nature-identical food colorants.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102477"},"PeriodicalIF":7.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S136759312400053X/pdfft?md5=550500d4cecdf2232739957a8c7489f4&pid=1-s2.0-S136759312400053X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141324568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
The non-catalytic domains of O-GlcNAc cycling enzymes present new opportunities for function-specific control O-GlcNAc 循环酶的非催化结构域为特异性功能控制提供了新机遇
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-10 DOI: 10.1016/j.cbpa.2024.102476
Chia-Wei Hu, Ke Wang, Jiaoyang Jiang
{"title":"The non-catalytic domains of O-GlcNAc cycling enzymes present new opportunities for function-specific control","authors":"Chia-Wei Hu,&nbsp;Ke Wang,&nbsp;Jiaoyang Jiang","doi":"10.1016/j.cbpa.2024.102476","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102476","url":null,"abstract":"<div><p>O-GlcNAcylation is an essential protein glycosylation governed by two O-GlcNAc cycling enzymes: O-GlcNAc transferase (OGT) installs a single sugar moiety <em>N-</em>acetylglucosamine (GlcNAc) on protein serine and threonine residues, and O-GlcNAcase (OGA) removes them. Aberrant O-GlcNAcylation has been implicated in various diseases. However, the large repertoire of more than 1000 O-GlcNAcylated proteins and the elusive mechanisms of OGT/OGA in substrate recognition present significant challenges in targeting the dysregulated O-GlcNAcylation for therapeutic development. Recently, emerging evidence suggested that the non-catalytic domains play critical roles in regulating the functional specificity of OGT/OGA via modulating their protein interactions and substrate recognition. Here, we discuss recent studies on the structures, mechanisms, and related tools of the OGT/OGA non-catalytic domains, highlighting new opportunities for function-specific control.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102476"},"PeriodicalIF":7.8,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Probing metalloenzyme dynamics in living systems: Contemporary advances in fluorescence imaging tools and applications 探测生命系统中金属酶的动态：荧光成像工具和应用的当代进展
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-08 DOI: 10.1016/j.cbpa.2024.102475
Sky Price, Emily L. Que
{"title":"Probing metalloenzyme dynamics in living systems: Contemporary advances in fluorescence imaging tools and applications","authors":"Sky Price,&nbsp;Emily L. Que","doi":"10.1016/j.cbpa.2024.102475","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102475","url":null,"abstract":"<div><p>Metalloenzymes are essential to cellular function, and their overexpression or enhanced activation are potential therapeutic targets. However, the study of metalloenzymes <em>in vitro</em> presents various challenges, leading many to develop tools to study them in their native cellular environment. Small-molecule fluorescence probes are commonly used to monitor metalloenzyme function, activity, and distribution <em>in situ</em>. These include probes that are activity-based (fluorescence is mediated by enzyme activity) or binding-based (fluorescence is mediated by interactions with the enzyme upon binding its metal cofactor). We discuss recent innovations that overcome key design challenges, such as the rapid diffusion of activity-based probes, the difficulty of probing redox-active enzymes, the selectivity of binding-based probes, and the poor penetration depth of fluorescence, and describe novel applications of these tools.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102475"},"PeriodicalIF":7.8,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141294167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 anchoring and fluorescent labeling in animals compatible with tissue clearing for 3D imaging 在动物体内进行分子锚定和荧光标记，与三维成像的组织清理兼容
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-06-04 DOI: 10.1016/j.cbpa.2024.102474
Takeharu Mino , Hiroshi Nonaka , Itaru Hamachi
{"title":"Molecular anchoring and fluorescent labeling in animals compatible with tissue clearing for 3D imaging","authors":"Takeharu Mino ,&nbsp;Hiroshi Nonaka ,&nbsp;Itaru Hamachi","doi":"10.1016/j.cbpa.2024.102474","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102474","url":null,"abstract":"<div><p>Analyzing the quantity and distribution of molecules throughout intact biological tissue is crucial for understanding various biological phenomena. Traditional methods involving destructive extraction result in the loss of spatial information. Conversely, tissue-clearing techniques combined with fluorescence imaging have recently emerged as a powerful tool for deep tissue imaging without sacrificing spatial coverage. Key to this approach is the anchoring and labeling of targets in intact tissue. In this review, methods for anchoring and labeling proteins, lipids, carbohydrates, and small molecules are presented. Future directions include the development of activity-based probes that work in vivo and mark transient events with spatial information to enable a deeper understanding of biological phenomena.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102474"},"PeriodicalIF":7.8,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000504/pdfft?md5=36af80453465d5781e5a415a7c90e9f8&pid=1-s2.0-S1367593124000504-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141251029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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