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Advances in chemoenzymatic synthesis of glycosaminoglycans and proteoglycans. 化学酶法合成糖胺聚糖和蛋白聚糖的研究进展。
IF 7.2 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-09-02 DOI: 10.1016/j.cbpa.2026.102753
Shahnaz Akhtar Nishat, Xuefei Huang
{"title":"Advances in chemoenzymatic synthesis of glycosaminoglycans and proteoglycans.","authors":"Shahnaz Akhtar Nishat, Xuefei Huang","doi":"10.1016/j.cbpa.2026.102753","DOIUrl":"https://doi.org/10.1016/j.cbpa.2026.102753","url":null,"abstract":"<p><p>Proteoglycans (PGs) are intricate macromolecules decorated with linear polysulfated glycosaminoglycans (GAGs) that play critical roles in orchestrating a wide range of physiological and pathological events. Advances in the utilization of recombinant enzymes and biosynthetic pathways have expedited the production of defined and homogeneous GAGs, helping overcome traditional barriers of chemical synthesis. Furthermore, the synthesis of GAG chains has been increasingly integrated with other critical structural elements, most notably the core proteins. Robust synthetic methodologies toward well-defined GAGs and entire PG structures are critical because there is a lack of comprehensive structure-function data that addresses the PG architecture as a unified glycoconjugate. The construction of homogeneous PG is a formidable and rapidly evolving frontier in chemical biology, and the latest developments in this arena are summarized in this review.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"94 ","pages":"102753"},"PeriodicalIF":7.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878933","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
Metalloadaptor and metallochaperone proteins reveal new chemical principles of biological metal homeostasis. 金属适应体和金属伴侣蛋白揭示了生物金属稳态的新化学原理。
IF 7.2 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-09-02 DOI: 10.1016/j.cbpa.2026.102761
Kelly Deng, Christopher J Chang
{"title":"Metalloadaptor and metallochaperone proteins reveal new chemical principles of biological metal homeostasis.","authors":"Kelly Deng, Christopher J Chang","doi":"10.1016/j.cbpa.2026.102761","DOIUrl":"https://doi.org/10.1016/j.cbpa.2026.102761","url":null,"abstract":"<p><p>Transition metals are essential nutrients that serve as metabolic cofactors and signaling agents in every cell type across all kingdoms of life. Owing to their relatively low abundance and high chemical reactivity, living organisms have evolved dedicated biochemical pathways to ensure active acquisition and targeted delivery of transition metals to their proper locations across biological length scales spanning tissues to cells to proteins, thus promoting beneficial physiology and avoiding detrimental pathology. Here we summarize recent advances in the discovery of copper metalloadaptor and zinc metallochaperone proteins that reveal new foundational chemical principles of biological metal homeostasis.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"94 ","pages":"102761"},"PeriodicalIF":7.2,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148878953","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
Design of programmable molecular interfaces for synthetic biology and therapeutic applications. 为合成生物学和治疗应用设计可编程分子接口。
IF 7.2 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-08-31 DOI: 10.1016/j.cbpa.2026.102759
Lennart Nickel, Ekaterina Pyatova, Bruno E Correia
{"title":"Design of programmable molecular interfaces for synthetic biology and therapeutic applications.","authors":"Lennart Nickel, Ekaterina Pyatova, Bruno E Correia","doi":"10.1016/j.cbpa.2026.102759","DOIUrl":"https://doi.org/10.1016/j.cbpa.2026.102759","url":null,"abstract":"<p><p>De novo protein design is reshaping how synthetic biology specifies and controls molecular function. Recent advances in generative modeling, sequence design and structure prediction enable molecular interactions to be created from scratch, reducing reliance on natural solutions and extensive experimental screening. These approaches support the design of compact, stable binding proteins, programmable interaction modules, and higher-order assemblies with defined geometry and regulatory behavior. As a result, de novo proteins are increasingly used to modulate signaling pathways, direct molecular targeting, and organize functional architectures across diverse biological contexts. Although challenges remain in predicting behavior in complex environments and balancing multiple design objectives, continued methodological progress is establishing de novo scaffolds as versatile, composable elements for the next-generation of synthetic biology.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"94 ","pages":"102759"},"PeriodicalIF":7.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862916","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 discovery of new enzymes in plant natural product biosynthesis. 植物天然产物生物合成中新酶的新发现。
IF 7.2 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-08-31 DOI: 10.1016/j.cbpa.2026.102752
Zheng-Xi Zhang, Han Ke, Jin Wang, Xiaoguang Lei
{"title":"Recent discovery of new enzymes in plant natural product biosynthesis.","authors":"Zheng-Xi Zhang, Han Ke, Jin Wang, Xiaoguang Lei","doi":"10.1016/j.cbpa.2026.102752","DOIUrl":"https://doi.org/10.1016/j.cbpa.2026.102752","url":null,"abstract":"<p><p>Plants are a vast reservoir of natural products with diverse structural scaffolds, making them an invaluable source for discovering novel enzymes that catalyze unique and evolutionarily specialized metabolic transformations in biosynthetic pathways. Rapid advances in genomics, metabolomics, protein structure prediction, and heterologous pathway reconstruction have enabled the identification of numerous cryptic biosynthetic enzymes responsible for key scaffold-forming and tailoring reactions in metabolism. Particularly notable are the discoveries of plant-derived enzymes that catalyze challenging chemical transformations, including oxidative carbon-carbon bond rearrangements, atypical cycloadditions, radical-mediated coupling reactions, and iterative scaffold remodeling. This review summarizes major advances in enzyme discovery in plant natural product biosynthesis in recent years, focusing on emerging catalytic mechanisms, strategies for elucidating pathways, and evolutionary relationships, and highlights their implications for synthetic biology, metabolic engineering, and the sustainable production of valuable natural products.</p>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"94 ","pages":"102752"},"PeriodicalIF":7.2,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148862892","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
Chemical strategies for trapping fleeting enzymatic complexes in nucleosome ubiquitylation 在核小体泛素化中捕获稍纵即逝的酶复合物的化学策略
IF 6.1 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-02-01 Epub Date: 2026-01-07 DOI: 10.1016/j.cbpa.2025.102651
Yun Liu, Qi Shu, Huasong Ai
{"title":"Chemical strategies for trapping fleeting enzymatic complexes in nucleosome ubiquitylation","authors":"Yun Liu,&nbsp;Qi Shu,&nbsp;Huasong Ai","doi":"10.1016/j.cbpa.2025.102651","DOIUrl":"10.1016/j.cbpa.2025.102651","url":null,"abstract":"<div><div>Site-specific ubiquitylation of nucleosomal histones, catalyzed by E3 ubiquitin ligase, plays a pivotal role in chromatin-templated processes, including transcriptional activation, gene silencing, and DNA damage repair. However, the inherently transient and dynamic interactions between the ubiquitin enzymes and the nucleosome substrate during the ubiquitylation cascade pose significant challenges to stabilizing functional complexes for structural and biochemical interrogation, thereby impeding mechanistic dissection. Recent advances in chemical biology strategies have emerged as powerful tools for resolving ternary ubiquitylation complexes of E3 ligase, E2∼Ub, and substrate. In this review, we systematically survey these innovative chemical approaches for trapping labile nucleosome ubiquitylation intermediates and consolidate the mechanistic insights into chromatin ubiquitylation biology.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"90 ","pages":"Article 102651"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145922194","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
Bridging or exchanging partners? A supramolecular perspective on bifunctional molecules and their potential for triggerable enzyme therapy 架桥还是交换伙伴？双功能分子的超分子视角及其在可触发酶治疗中的潜力。
IF 6.1 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-02-01 Epub Date: 2026-01-06 DOI: 10.1016/j.cbpa.2025.102650
Leila Motiei, Martín López-Vidal, David Margulies
{"title":"Bridging or exchanging partners? A supramolecular perspective on bifunctional molecules and their potential for triggerable enzyme therapy","authors":"Leila Motiei,&nbsp;Martín López-Vidal,&nbsp;David Margulies","doi":"10.1016/j.cbpa.2025.102650","DOIUrl":"10.1016/j.cbpa.2025.102650","url":null,"abstract":"<div><div>Bifunctional molecules are commonly regarded as proximity-inducing compounds (PICs) that bridge two proteins to generate novel biological outcomes. Here, we highlight a distinct and emerging subclass, termed partner-exchanging molecules (PEMs), which cannot bind both protein partners simultaneously. Instead, they act through a partner-swapping mechanism, enabling one protein to unnaturally activate another. This perspective examines their mechanisms of action and surveys potential applications such as protein sensing, prodrug activation, controlled release, and the reconfiguration of intracellular signaling. Because PEMs offer a simple route to build triggerable enzymes, we further discuss them in the context of artificial zymogens, emphasizing their promise to mediate activation of therapeutic proenzyme systems via non-enzyme proteins and to render native enzymes triggerable in cells. By positioning PEMs as a conceptual link between bifunctional molecules and artificial zymogens, we aim to broaden our understanding of bifunctional regulators and expand the scope of artificial proenzyme design.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"90 ","pages":"Article 102650"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145916338","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
Small RNAs, big potential: Engineering microRNA-based synthetic gene circuits 小rna，大潜力：基于微rna的合成基因电路工程
IF 6.1 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-02-01 Epub Date: 2026-01-31 DOI: 10.1016/j.cbpa.2026.102652
Archismita Kundu , Roman Jerala
{"title":"Small RNAs, big potential: Engineering microRNA-based synthetic gene circuits","authors":"Archismita Kundu ,&nbsp;Roman Jerala","doi":"10.1016/j.cbpa.2026.102652","DOIUrl":"10.1016/j.cbpa.2026.102652","url":null,"abstract":"<div><div>MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression. Their dysregulation is closely associated with various diseases, positioning them as biomarkers of cellular state. Synthetic biology has leveraged these properties to engineer miR-based genetic circuits capable of sensing and interpreting endogenous miR levels. Early miR-OFF systems relied on reporter gene repression but were limited by ambiguous signal interpretation. Subsequent advances introduced miR-ON architectures, logic-based classifiers integrating multiple miRs, and layered regulatory strategies combining transcriptional, translational, and cleavage-based modules to enhance sensitivity and specificity. Recent innovations include CRISPR-associated miR-responsive systems and incoherent feed-forward loop (iFFL) architectures that stabilize gene expression amid cellular variability, shifting applications from passive sensing to therapeutic intervention. Despite challenges such as leakage, cellular resource resources, and delivery, progress in orthogonal miR toolkits, computational modeling, and RNA-based delivery platforms is rapidly driving miR-based circuits toward diagnostic and therapeutic applications.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"90 ","pages":"Article 102652"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073750","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
Chemical dissection of microbiology and microbiota 微生物学和微生物群的化学解剖
IF 6.1 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-02-01 Epub Date: 2025-12-24 DOI: 10.1016/j.cbpa.2025.102641
Catherine L. Grimes, Howard C. Hang
{"title":"Chemical dissection of microbiology and microbiota","authors":"Catherine L. Grimes,&nbsp;Howard C. Hang","doi":"10.1016/j.cbpa.2025.102641","DOIUrl":"10.1016/j.cbpa.2025.102641","url":null,"abstract":"","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"90 ","pages":"Article 102641"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145808451","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 biology for phytohormone production 植物激素合成生物学
IF 6.1 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2026-02-01 Epub Date: 2025-12-27 DOI: 10.1016/j.cbpa.2025.102649
Pattarawan Intasian , Ninlapan Kimprasoot , Duangthip Trisrivirat, Pimchai Chaiyen
{"title":"Synthetic biology for phytohormone production","authors":"Pattarawan Intasian ,&nbsp;Ninlapan Kimprasoot ,&nbsp;Duangthip Trisrivirat,&nbsp;Pimchai Chaiyen","doi":"10.1016/j.cbpa.2025.102649","DOIUrl":"10.1016/j.cbpa.2025.102649","url":null,"abstract":"<div><div>Phytohormones are compounds produced by plants that can control the processes of plant development and are involved in defense mechanisms. They can serve as sustainable enhancers for plant growth and are also better alternatives to agrochemicals because of their bio-based nature and optimal safety profile towards mammalian cells. Although phytohormones are essential for plant growth, they are naturally synthesized by plants in varying quantities, influenced both by environmental and genetic factors. The synthesis of phytohormones, however, faces several hurdles, including challenges in optimizing the production process as well as difficulties in the extraction of these compounds for downstream applications. In this review, we critically evaluate synthetic biology approaches for phytohormone production, which provides a sustainable method for the production of important phytohormones including auxin, gibberellin (GA), and salicylic acid (SA). These three compounds are highly significant for the agricultural industry because of their widespread utilization.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"90 ","pages":"Article 102649"},"PeriodicalIF":6.1,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839135","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
Emerging trends in chemoproteomics: Mapping the landscape of protein–metabolite interactions 化学蛋白质组学的新趋势：绘制蛋白质-代谢物相互作用的景观
IF 6.1 2区 生物学
Current Opinion in Chemical Biology Pub Date : 2025-12-01 Epub Date: 2025-09-25 DOI: 10.1016/j.cbpa.2025.102631
Ning Wan , Chenguang Liu , Haiping Hao , Hui Ye
{"title":"Emerging trends in chemoproteomics: Mapping the landscape of protein–metabolite interactions","authors":"Ning Wan ,&nbsp;Chenguang Liu ,&nbsp;Haiping Hao ,&nbsp;Hui Ye","doi":"10.1016/j.cbpa.2025.102631","DOIUrl":"10.1016/j.cbpa.2025.102631","url":null,"abstract":"<div><div>Protein-metabolite interactions (PMIs) are fundamental regulators of cellular metabolism, influencing essential processes such as energy homeostasis, signal transduction, and gene expression. However, their transient and dynamic nature presents significant challenges for detection. Chemoproteomics has emerged as a powerful and versatile strategy for capturing and characterizing PMIs with proteome-wide resolution. These approaches can be broadly categorized into derivatization-based methods, which utilize chemically modified probes to enrich protein targets, and derivatization-free methods, which detect changes in protein physicochemical properties upon metabolite binding, aided by highly sensitive proteomic analysis. In this review, we discuss recent advancements in both strategies, highlighting their applications in mapping PMIs and their potential to deepen our understanding of cellular metabolism and disease mechanisms.</div></div>","PeriodicalId":291,"journal":{"name":"Current Opinion in Chemical Biology","volume":"89 ","pages":"Article 102631"},"PeriodicalIF":6.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145134890","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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