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Optogenetic engineering for ion channel modulation
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-03 DOI: 10.1016/j.cbpa.2025.102569
Tianlu Wang , Tatsuki Nonomura , Tien-Hung Lan , Yubin Zhou
{"title":"Optogenetic engineering for ion channel modulation","authors":"Tianlu Wang ,&nbsp;Tatsuki Nonomura ,&nbsp;Tien-Hung Lan ,&nbsp;Yubin Zhou","doi":"10.1016/j.cbpa.2025.102569","DOIUrl":"10.1016/j.cbpa.2025.102569","url":null,"abstract":"<div><div>Optogenetics, which integrates photonics and genetic engineering to control protein activity and cellular processes, has transformed biomedical research. Its precise spatiotemporal control, minimal invasiveness, and tunable reversibility have spurred its widespread adoption in both basic and clinical research. Optogenetic techniques have been applied to partially restore vision in blind patients and are being actively explored as innovative treatments for neurological, psychiatric, cardiac, and immunological disorders. Microbial channelrhodopsins (ChRs) allow precise manipulation of neuronal and cardiac activities, while vertebrate rhodopsins offer unique opportunities for ion channel modulation through G-protein-coupled receptor (GPCR) pathways. Plant-derived photoswitchable domains can also be engineered into ion channels to confer photosensitivity. This review summarizes the latest progress in engineering genetically encoded light-sensitive ion channel actuators and modulators (GELICAMs) with diverse ion selectivity and spectral sensitivity. We further discuss the potential applications and challenges of these tools in advancing biomedical research and therapeutic interventions.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"85 ","pages":"Article 102569"},"PeriodicalIF":6.9,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132999","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
Developing photoactivated artificial enzymes for sustainable fuel production 开发用于可持续燃料生产的光激活人工酶。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102553
Ashlee E. Wertz , Hannah S. Shafaat
{"title":"Developing photoactivated artificial enzymes for sustainable fuel production","authors":"Ashlee E. Wertz ,&nbsp;Hannah S. Shafaat","doi":"10.1016/j.cbpa.2024.102553","DOIUrl":"10.1016/j.cbpa.2024.102553","url":null,"abstract":"<div><div>Enzymes catalyze molecular reactions with remarkable efficiency and selectivity under mild conditions. Photoactivated enzymes make use of a light-absorbing chromophore to drive chemical transformations, ideally using sunlight as an energy source. The direct attachment of a chromophore to native enzymes is advantageous, as information on the underlying catalytic mechanisms can be obtained. Artificial enzyme development seeks to mimic natural enzymes to generate valuable products with high efficiency in a simplified, robust framework. Light-initiated artificial enzymatic catalysis combines these strategies and represents a promising avenue for sustainable generation of value-added products. Furthermore, while early systems often combined three components for catalysis-- the enzyme, a photosensitizer, and a sacrificial electron donor-- we describe an adaptation of this approach in which the chromophore is immobilized on the enzyme, removing the need for diffusional collision. The latter is advantageous as it provides deeper insight into the catalytic mechanism and facilitates further optimization of the designed construct. In this opinion, we highlight several examples of light-driven, artificial metalloenzymes, and suggest that ongoing and future efforts should leverage prior mechanistic studies on native enzymes as a foundation for strategic design of next-generation photoactivated protein-based catalysts.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102553"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906428","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
Bacterial peptidoglycan as a living polymer 细菌肽聚糖是一种活的聚合物。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102562
Amr M. El-Araby, Jed F. Fisher, Shahriar Mobashery
{"title":"Bacterial peptidoglycan as a living polymer","authors":"Amr M. El-Araby,&nbsp;Jed F. Fisher,&nbsp;Shahriar Mobashery","doi":"10.1016/j.cbpa.2024.102562","DOIUrl":"10.1016/j.cbpa.2024.102562","url":null,"abstract":"<div><div>The peptidoglycan manifests as a multifaceted component of the bacterial cell wall. Throughout the lifecycle of the bacterium, the peptidoglycan is deconstructed, rebuilt, and remodeled for bacterial cell growth and replication. Degradation products of the peptidoglycan serve as precursors for cell-wall building blocks <em>via</em> recycling processes and as signaling molecules. Cell-wall recycling and <em>de novo</em> cell-wall synthesis converge biochemically at the cytoplasmic compartment. Peptidoglycan biochemistry is finely tuned to maintain the polymer's functions and is intimately connected to antibiotic-resistance mechanisms. Cell-wall-modifying enzymes present a unique opportunity for the discovery of antibiotics and antibiotic adjuvants. The unique chemical template of the peptidoglycan has been a target of numerous chemical biology approaches for investigating its functions and modulation. In this review, we highlight the current perspective on peptidoglycan research. We present recent efforts to understand the peptidoglycan as a functional component of antibiotic resistance, and as a target for antimicrobial therapy.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102562"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862589","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
Illuminating anions in biology with genetically encoded fluorescent biosensors 用基因编码荧光生物传感器照亮生物学中的阴离子。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102548
Mariah A. Cook , Shelby M. Phelps , Jasmine N. Tutol , Derik A. Adams, Sheel C. Dodani
{"title":"Illuminating anions in biology with genetically encoded fluorescent biosensors","authors":"Mariah A. Cook ,&nbsp;Shelby M. Phelps ,&nbsp;Jasmine N. Tutol ,&nbsp;Derik A. Adams,&nbsp;Sheel C. Dodani","doi":"10.1016/j.cbpa.2024.102548","DOIUrl":"10.1016/j.cbpa.2024.102548","url":null,"abstract":"<div><div>Anions are critical to all life forms. Anions can be absorbed as nutrients or biosynthesized. Anions shape a spectrum of fundamental biological processes at the organismal, cellular, and subcellular scales. Genetically encoded fluorescent biosensors can capture anions in action across time and space dimensions with microscopy. The firsts of such technologies were reported more than 20 years for monoatomic chloride and polyatomic cAMP anions. However, the recent boom of anion biosensors illuminates the unknowns and opportunities that remain for toolmakers and end users to meet across the aisle to spur innovations in biosensor designs and applications for discovery anion biology. In this review, we will canvas progress made over the last three years for biologically relevant anions that are classified as halides, oxyanions, carboxylates, and nucleotides.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102548"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805597","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
Enabling structural biological electron paramagnetic resonance spectroscopy in membrane proteins through spin labelling 通过自旋标记实现膜蛋白结构生物电子顺磁共振波谱。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102564
Anokhi Shah , Joshua L. Wort , Yue Ma , Christos Pliotas
{"title":"Enabling structural biological electron paramagnetic resonance spectroscopy in membrane proteins through spin labelling","authors":"Anokhi Shah ,&nbsp;Joshua L. Wort ,&nbsp;Yue Ma ,&nbsp;Christos Pliotas","doi":"10.1016/j.cbpa.2024.102564","DOIUrl":"10.1016/j.cbpa.2024.102564","url":null,"abstract":"<div><div>Pulsed dipolar electron paramagnetic resonance spectroscopy (PDS), combined with site-directed spin-labelling, represents a powerful tool for the investigation of biomacromolecules, emerging as a keystone approach in structural biology. Increasingly, PDS is applied to study highly complex integral membrane protein systems, such as mechanosensitive ion channels, transporters, G-protein coupled receptors, ion pumps, and outer membrane proteins elucidating their dynamics and revealing conformational ensembles. Indeed, PDS offers a platform to study intermediate or lowly-populated states that are otherwise invisible to other modern methods, such as X-ray crystallography, cryo-EM, and hydrogen-deuterium exchange-mass spectrometry. Importantly, advances in spin labelling strategies welcome a new era of membrane protein investigation under near-native or in-cell conditions. Here, we review recent integral membrane protein PDS applications, and highlight well-suited, emerging spin labelling strategies that show promise for future studies.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102564"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875665","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
Small molecules as modulators of phage–bacteria interactions 小分子作为噬菌体与细菌相互作用的调节剂。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102566
Joel W.H. Wong , Emily P. Balskus
{"title":"Small molecules as modulators of phage–bacteria interactions","authors":"Joel W.H. Wong ,&nbsp;Emily P. Balskus","doi":"10.1016/j.cbpa.2024.102566","DOIUrl":"10.1016/j.cbpa.2024.102566","url":null,"abstract":"<div><div>Bacteriophages (phages) play a critical role in microbial ecology and evolution. Their interactions with bacteria are influenced by a complex network of chemical signals derived from a wide range of sources including both endogenous bacterial metabolites and exogenous environmental compounds. In this review, we highlight two areas where small molecules play a pivotal role in modulating phage behaviors. First, we discuss how temperate phages respond to various chemical cues that influence the lysis-lysogeny decision, describing recent advances in our understanding of noncanonical cues. Second, we examine the diverse array of small molecules that disrupt phage infection, potentially serving as bacterial defense strategies against their long-standing competitors. Collectively, this growing body of research highlights the intricate molecular mechanisms governing phage-bacteria dynamics, offering new perspectives on the chemical language shaping microbial communities.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102566"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906429","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
Advances in acid-degradable and enzyme-cleavable linkers for drug delivery 酸可降解和酶可切割药物传递连接体的研究进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102552
Sheng Zhao , Na Yu , Hesong Han , Shutao Guo , Niren Murthy
{"title":"Advances in acid-degradable and enzyme-cleavable linkers for drug delivery","authors":"Sheng Zhao ,&nbsp;Na Yu ,&nbsp;Hesong Han ,&nbsp;Shutao Guo ,&nbsp;Niren Murthy","doi":"10.1016/j.cbpa.2024.102552","DOIUrl":"10.1016/j.cbpa.2024.102552","url":null,"abstract":"<div><div>Drug delivery vectors have the potential to improve the efficacy of therapeutics, including small molecules and nucleic acid-based drugs. However, challenges remain in developing linkages that enable the precise and efficient release of therapeutic cargo in response to mildly acidic environments or lysosomal enzymes. This review highlights recent advances in acid-degradable acetal/ketal and enzyme-cleavable linkages for endolysosomal release. These innovations include the developments of azido-acetal linkers with improved stability and hydrolysis kinetics, organocatalytic trans-isopropenylation for synthesizing asymmetric ketals and their applications in drug delivery, and enzyme-cleavable linkers activated by cathepsin B or <em>β</em>-galactosidase.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102552"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789441","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
Peptide toxins as tools in ion channel biology 肽毒素作为离子通道生物学的工具。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102568
Sucheta Bandyopadhyay , Satyajit Mishra , Jeet Kalia
{"title":"Peptide toxins as tools in ion channel biology","authors":"Sucheta Bandyopadhyay ,&nbsp;Satyajit Mishra ,&nbsp;Jeet Kalia","doi":"10.1016/j.cbpa.2024.102568","DOIUrl":"10.1016/j.cbpa.2024.102568","url":null,"abstract":"<div><div>Animal venom contains ion channel-targeting peptide toxins that inflict paralysis or pain. The high specificity and potency of these toxins for their target ion channels provides enticing opportunities for their deployment as tools in channel biology. Mechanistic studies on toxin-mediated ion channel modulation have yielded landmark breakthroughs in our understanding of channel architectures and gating mechanisms. Toxins have been recently repurposed as powerful structural biology probes to obtain structures of ion channels in elusive toxin-stabilized conformations providing unprecedented insights into channel gating. Insightful glimpses of protein–lipid interactions provided by some of these structures have served as blueprints for electrophysiology-based studies aimed at elucidating the functional roles of these interactions. Moreover, toxins appended with fluorophores have been used for clinical, biophysical, and cell biology-based studies. Herein, we summarize the contributions of ion channel-targeting toxins as tools in voltage-gated ion channel and transient receptor potential channel biology.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102568"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925853","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
Microbial metabolism of host-derived antioxidants 宿主来源抗氧化剂的微生物代谢。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102565
Zhe Zhou , Stavroula K. Hatzios
{"title":"Microbial metabolism of host-derived antioxidants","authors":"Zhe Zhou ,&nbsp;Stavroula K. Hatzios","doi":"10.1016/j.cbpa.2024.102565","DOIUrl":"10.1016/j.cbpa.2024.102565","url":null,"abstract":"<div><div>Humans are exposed to a wide variety of small molecules with antioxidant properties that are poorly metabolized by mammalian cells. However, gastrointestinal microbes encode enzymes that convert these redox-active molecules into nutrient sources and electron acceptors to support bacterial growth in the gut. Here, we describe recent studies highlighting how microbial metabolism of host-derived antioxidants modulates interspecies interactions and provide an overview of the interdisciplinary approaches being used to map these metabolic pathways <em>in vivo</em>. Uncovering microbe-driven biotransformations of redox-active small molecules could create new opportunities to improve human health by modulating redox reactions at the host–microbe interface.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102565"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142890863","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
Synthetic ion channels made of DNA 由DNA合成的离子通道。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-02-01 DOI: 10.1016/j.cbpa.2024.102567
Ran Tivony
{"title":"Synthetic ion channels made of DNA","authors":"Ran Tivony","doi":"10.1016/j.cbpa.2024.102567","DOIUrl":"10.1016/j.cbpa.2024.102567","url":null,"abstract":"<div><div>Natural ion channels have long inspired the design of synthetic nanopores with protein-like features. A significant leap towards this endeavor has been made possible using DNA origami. The exploitation of DNA as a building material has enabled the construction of biomimetic DNA nanopores with a range of pore dimensions and stimuli-responsive capabilities. However, structural fluctuations and ion leakage across the walls of DNA nanopores greatly limit their use in various applications like label-free sensing and as a research tool in functional studies of ion channels. This review outlines some of the guiding principles for biomimetic engineering of DNA-based ion channels, discusses the weaknesses of current DNA nanopore designs, and presents recent efforts to alleviate these limitations.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"84 ","pages":"Article 102567"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913235","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
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