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From the forest floor to the lab: Insights into the diversity and complexity of mushroom polyketide synthases 从林地到实验室：洞察蘑菇多酮合成酶的多样性和复杂性。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-10-01 Epub Date: 2024-08-10 DOI: 10.1016/j.cbpa.2024.102510
Nikolai A. Löhr , Lukas Platz , Dirk Hoffmeister , Michael Müller
{"title":"From the forest floor to the lab: Insights into the diversity and complexity of mushroom polyketide synthases","authors":"Nikolai A. Löhr ,&nbsp;Lukas Platz ,&nbsp;Dirk Hoffmeister ,&nbsp;Michael Müller","doi":"10.1016/j.cbpa.2024.102510","DOIUrl":"10.1016/j.cbpa.2024.102510","url":null,"abstract":"<div><p>Mushroom-forming fungi exhibit a distinctive ecology, which is unsurprisingly also reflected in unique and divergent biosynthetic pathways. We review this phenomenon through the lens of the polyketide metabolism, where mushrooms often deviate from established principles and challenge conventional paradigms. This is evident not only by non-canonical enzyme architectures and functions but also by their propensity for multi-product synthases rather than single-product pathways. Nevertheless, mushrooms also feature many polyketides familiar from plants, bacteria, and fungi of their sister division Ascomycota, which, however, are the result of an independent evolution. In this regard, the captivating biosynthetic pathways of mushrooms might even help us understand the biological pressures that led to the simultaneous production of the same natural products (via convergent evolution, co-evolution, and/or metaevolution) and thus address the question of their <em>raison d'être</em>.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"82 ","pages":"Article 102510"},"PeriodicalIF":6.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000863/pdfft?md5=fa57ba35ff5b4bbb74531c3b64a4107a&pid=1-s2.0-S1367593124000863-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141915684","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 progresses in the cyclization and oxidation of polyketide biosynthesis 多酮生物合成的环化和氧化的最新进展。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-08-03 DOI: 10.1016/j.cbpa.2024.102507
Bo Zhang, Hui Ming Ge
{"title":"Recent progresses in the cyclization and oxidation of polyketide biosynthesis","authors":"Bo Zhang,&nbsp;Hui Ming Ge","doi":"10.1016/j.cbpa.2024.102507","DOIUrl":"10.1016/j.cbpa.2024.102507","url":null,"abstract":"<div><p>Polyketides represent an important class of natural products, renowned for their intricate structures and diverse biological activities. In contrast to common fatty acids, polyketides possess relatively more rigid carbon skeletons, more complex ring systems, and chiral centers. These structural features are primarily achieved through distinctive enzymatic cyclizations and oxidations as tailoring steps. In this opinion, we discuss the recent progress in deciphering the mechanisms of cyclization and oxidation within polyketide biosynthesis. By shedding light on these enzymatic processes, this article seeks to motivate the community to unravel the remaining mysteries surrounding cyclase and oxidase functionalities and to explore novel polyketide natural products through genome mining.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102507"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887844","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
Strategies and mechanisms for endosomal escape of therapeutic nucleic acids 治疗性核酸的内体逸出策略和机制。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-08-02 DOI: 10.1016/j.cbpa.2024.102506
Melina Grau , Ernst Wagner
{"title":"Strategies and mechanisms for endosomal escape of therapeutic nucleic acids","authors":"Melina Grau ,&nbsp;Ernst Wagner","doi":"10.1016/j.cbpa.2024.102506","DOIUrl":"10.1016/j.cbpa.2024.102506","url":null,"abstract":"<div><p>Despite impressive recent establishment of therapeutic nucleic acids as drugs and vaccines, their broader medical use is impaired by modest performance in intracellular delivery. Inefficient endosomal escape presents a major limitation responsible for inadequate cytosolic cargo release. Depending on the carrier, this endosomal barrier can strongly limit or even abolish nucleic acid delivery. Different recent endosomal escape strategies and their hypothesized mechanisms are reviewed.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102506"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000826/pdfft?md5=2b89c2b69ecf385ac782b8ed8112060e&pid=1-s2.0-S1367593124000826-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141887845","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
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 : 2024-08-01 Epub 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":"2024-08-01","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
Glycoengineering in antigen-specific immunotherapies 抗原特异性免疫疗法中的糖工程。
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-07-24 DOI: 10.1016/j.cbpa.2024.102503
Yuxin Li , Hongming Chen , Jiuxiang Gao , Peng Wu , Senlian Hong
{"title":"Glycoengineering in antigen-specific immunotherapies","authors":"Yuxin Li ,&nbsp;Hongming Chen ,&nbsp;Jiuxiang Gao ,&nbsp;Peng Wu ,&nbsp;Senlian Hong","doi":"10.1016/j.cbpa.2024.102503","DOIUrl":"10.1016/j.cbpa.2024.102503","url":null,"abstract":"<div><p>Advances in immunotherapy have revolutionized modern medical care paradigms. However, many patients respond poorly to the current FDA-approved treatment regimens that primarily target protein-based antigens or checkpoints. Current progress in developing therapeutic strategies that target disease-associated glycans has pinpointed a new class of glycoimmune checkpoints that function orthogonally to the established protein-immune checkpoints. Glycoengineering using chemical, enzymatic, and genetic methods is also increasingly recognized for its massive potential to improve biopharmaceuticals, such as tailoring therapies with antigen-targeting agents. Here, we review the recent development and applications of glycoengineering of antibodies and cells to suit therapeutic applications. We highlight living-cell glycoengineering strategies on cancer and immune cells for better therapeutic efficacy against specific antigens by leveraging the pre-existing immune machinery or instructing <em>de novo</em> creation of targeting agents. We also discuss glycoengineering strategies for studying basic immuno-oncology. Collectively, glycoengineering has a significant contribution to the design of antigen-specific immunotherapies.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102503"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756041","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
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 : 2024-08-01 Epub 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":"2024-08-01","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
Recent strides in macromolecular targeted photodynamic therapy for cancer 癌症大分子靶向光动力疗法的最新进展
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-07-05 DOI: 10.1016/j.cbpa.2024.102497
Maxwell B. Quaye, Girgis Obaid
{"title":"Recent strides in macromolecular targeted photodynamic therapy for cancer","authors":"Maxwell B. Quaye,&nbsp;Girgis Obaid","doi":"10.1016/j.cbpa.2024.102497","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102497","url":null,"abstract":"<div><p>The recent approval of Akalux® for antibody-targeted photodynamic therapy (PDT) in Japan (also known as photoimmunotherapy), and the recent approval of Cytalux® for folate-specific image guided surgery by the FDA have motivated the continued development of macromolecular targeted PDT for cancer management. This review spotlights some of the most recent advances in macromolecular targeted PDT since 2021, exploring the latest advances in protein engineering, adaptive macromolecular constructs and nanotechnology, adoption of immune checkpoint inhibitors, and targeting using biomimetic membranes. These strategies summarized here attempt to expand the functionality, benefit, and success of macromolecular targeting for PDT to advance the technology beyond what has already entered into the clinical realm.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102497"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000735/pdfft?md5=abb39fc10d3de6fdc5c0ae66b349a979&pid=1-s2.0-S1367593124000735-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141543003","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 : 2024-08-01 Epub 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":"2024-08-01","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
Biosynthesis of isonitrile lipopeptides 异腈脂肽的生物合成
IF 7.8 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI: 10.1016/j.cbpa.2024.102470
Kaimin Jia , Helen Sun , Yiyan Zhou , Wenjun Zhang
{"title":"Biosynthesis of isonitrile lipopeptides","authors":"Kaimin Jia ,&nbsp;Helen Sun ,&nbsp;Yiyan Zhou ,&nbsp;Wenjun Zhang","doi":"10.1016/j.cbpa.2024.102470","DOIUrl":"https://doi.org/10.1016/j.cbpa.2024.102470","url":null,"abstract":"<div><p>Isonitrile lipopeptides discovered from Actinobacteria have attracted wide attention due to their fascinating biosynthetic pathways and relevance to the virulence of many human pathogens including <em>Mycobacterium tuberculosis</em>. Specifically, the identification of the new class of isonitrile-forming enzymes that belong to non-heme iron (II) and α-ketoglutarate dependent dioxygenases has intrigued several research groups to investigate their catalytic mechanism. Here we summarize the recent studies on the biosynthesis of isonitrile lipopeptides from <em>Streptomyces</em> and <em>Mycobacterium</em>. The latest research on the core and tailoring enzymes involved in the pathway as well as the isonitrile metabolic enzymes are discussed in this review.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102470"},"PeriodicalIF":7.8,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090176","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
MicroRNA:Siglec crosstalk in cancer progression 微 RNA：Siglec 在癌症进展中的相互影响
IF 6.9 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2024-08-01 Epub Date: 2024-07-18 DOI: 10.1016/j.cbpa.2024.102502
D. Mustafov , M.S. Ahmad , A. Serrano , M. Braoudaki , S.S. Siddiqui
{"title":"MicroRNA:Siglec crosstalk in cancer progression","authors":"D. Mustafov ,&nbsp;M.S. Ahmad ,&nbsp;A. Serrano ,&nbsp;M. Braoudaki ,&nbsp;S.S. Siddiqui","doi":"10.1016/j.cbpa.2024.102502","DOIUrl":"10.1016/j.cbpa.2024.102502","url":null,"abstract":"<div><p>Aberrant Siglec expression in the tumour microenvironment has been implicated in tumour malignancies and can impact tumour behaviour and patient survival. Further to this, engagement with sialoglycans induces masked antigen recognition and promotes immune evasion, highlighting deregulated immune function. This necessitates the elucidation of their expression profiles in tumour progression. MicroRNAs (miRNAs) mediated targeting represents a novel approach to further elucidate Siglec potential and clinical relevance. Although miRNA activity in Siglec expression remains limited, we highlight current literature detailing miRNA:Siglec interactions within the tumour landscape and provide insights for possible diagnostic and therapeutic strategies in targeting the Siglec/sialic acid axis.</p></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"81 ","pages":"Article 102502"},"PeriodicalIF":6.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1367593124000784/pdfft?md5=fa5f5ed0a0c37a6bae4a3703795bb511&pid=1-s2.0-S1367593124000784-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141637816","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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