Current Opinion in Chemical Biology最新文献

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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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2026-02-01 DOI: 10.1016/j.cbpa.2026.102652

Archismita Kundu , Roman Jerala

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.

MicroRNAs （miRs）是调节基因表达的小的非编码rna。它们的失调与多种疾病密切相关，是细胞状态的生物标志物。合成生物学利用这些特性来设计基于miR的遗传电路，能够感知和解释内源性miR水平。早期的miR-OFF系统依赖于报告基因抑制，但受到模糊信号解释的限制。随后的进展引入了miR-ON架构、整合多个mir的基于逻辑的分类器，以及结合转录、翻译和切割模块的分层调节策略，以提高灵敏度和特异性。最近的创新包括crispr相关的mir响应系统和非相干前馈环路（iFFL）架构，这些架构稳定了细胞变异性中的基因表达，将应用从被动感知转变为治疗干预。尽管存在诸如泄漏、细胞资源资源和递送等挑战，但正交miR工具包、计算建模和基于rna的递送平台的进展正在迅速推动基于miR的电路向诊断和治疗应用方向发展。

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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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2026-01-07 DOI: 10.1016/j.cbpa.2025.102651

Yun Liu, Qi Shu, Huasong Ai

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.

由E3泛素连接酶催化的核小体组蛋白位点特异性泛素化在染色质模板化过程中起着关键作用，包括转录激活、基因沉默和DNA损伤修复。然而，在泛素化级联过程中，泛素酶和核小体底物之间固有的瞬态和动态相互作用对稳定结构和生化询问的功能复合物构成了重大挑战，从而阻碍了机械解剖。化学生物学策略的最新进展已经成为解决E3连接酶、E2 ~ Ub和底物三元泛素化复合物的有力工具。在这篇综述中，我们系统地综述了这些捕获不稳定核小体泛素化中间体的创新化学方法，并巩固了染色质泛素化生物学的机制见解。

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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2026-01-06 DOI: 10.1016/j.cbpa.2025.102650

Leila Motiei, Martín López-Vidal, David Margulies

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.

双功能分子通常被认为是连接两种蛋白质产生新的生物学结果的接近诱导化合物（PICs）。在这里，我们强调了一个独特的新兴亚类，称为伴侣交换分子（PEMs），它不能同时结合两个蛋白质伴侣。相反，它们通过伴侣交换机制起作用，使一种蛋白质非自然地激活另一种蛋白质。这一观点探讨了它们的作用机制，并调查了潜在的应用，如蛋白质传感、前药激活、控制释放和细胞内信号的重新配置。由于PEMs提供了一种构建可触发酶的简单途径，我们进一步在人工酶原的背景下讨论它们，强调它们通过非酶蛋白介导治疗性酶原系统的激活，并使细胞中的天然酶可触发。通过将PEMs定位为双功能分子和人工酶原之间的概念联系，我们的目标是拓宽我们对双功能调节剂的理解，扩大人工酶原设计的范围。

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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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2025-12-27 DOI: 10.1016/j.cbpa.2025.102649

Pattarawan Intasian , Ninlapan Kimprasoot , Duangthip Trisrivirat, Pimchai Chaiyen

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.

植物激素是由植物产生的能够控制植物发育过程并参与防御机制的化合物。它们可以作为植物生长的可持续促进剂，而且由于其生物基性质和对哺乳动物细胞的最佳安全性，它们也是农用化学品的更好替代品。虽然植物激素对植物生长至关重要，但受环境和遗传因素的影响，植物可以自然合成不同数量的植物激素。然而，植物激素的合成面临着一些障碍，包括优化生产过程的挑战以及提取这些化合物用于下游应用的困难。在这篇综述中，我们批判性地评价了植物激素生产的合成生物学方法，为生长素、赤霉素（GA）和水杨酸（SA）等重要植物激素的生产提供了一种可持续的方法。这三种化合物的广泛应用对农业具有重要意义。

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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2025-12-24 DOI: 10.1016/j.cbpa.2025.102641

Catherine L. Grimes, Howard C. Hang

引用次数: 0

Editorial Overview: Converging innovations in chemical proteomics 编辑概述：化学蛋白质组学的融合创新。

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2025-11-19 DOI: 10.1016/j.cbpa.2025.102640

Jing Yang, Wenqing Shui

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 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2025-09-25 DOI: 10.1016/j.cbpa.2025.102631

Ning Wan , Chenguang Liu , Haiping Hao , Hui Ye

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.

蛋白质-代谢物相互作用（pmi）是细胞代谢的基本调节因子，影响能量稳态、信号转导和基因表达等基本过程。然而，它们的瞬态和动态性给检测带来了重大挑战。化学蛋白质组学已经成为一种强大而通用的策略，用于捕获和表征具有蛋白质组级分辨率的PMIs。这些方法可以大致分为基于衍生化的方法，利用化学修饰的探针来丰富蛋白质靶点，以及无衍生化的方法，在高度敏感的蛋白质组学分析的辅助下，检测代谢物结合时蛋白质物理化学性质的变化。在这篇综述中，我们讨论了这两种策略的最新进展，强调了它们在PMIs制图中的应用，以及它们加深我们对细胞代谢和疾病机制的理解的潜力。

引用次数: 0

In vivo cross-linking mass spectrometry: Advances and challenges in decoding protein conformational dynamics and complex regulatory networks in living cells 体内交联质谱：解码活细胞中蛋白质构象动力学和复杂调节网络的进展和挑战

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2025-09-12 DOI: 10.1016/j.cbpa.2025.102630

Jing Chen , Qun Zhao , Yukui Zhang , Lihua Zhang

In vivo chemical cross-linking mass spectrometry (XL-MS) has emerged as a powerful technique for high-throughput, proteome-wide mapping of intramolecular conformations and intermolecular interactions of protein complexes in living cells. By providing distance constraints between specific residues, XL-MS enables the characterization of protein conformations and interaction networks under near-physiological conditions, greatly facilitating the analysis of biomacromolecular functions and regulatory mechanisms. The information obtained from cross-linking is particularly valuable at the systems level, and its value continues to increase with improvements in the density of cross-link identification, the precision of distance constraints, and the spatiotemporal resolution. In recent years, advances in cross-linker design, cross-linked peptide enrichment methods, mass spectrometry analysis, and artificial intelligence-assisted data analysis have significantly expanded the capabilities of in vivo XL-MS. This article systematically reviews the latest progress in in vivo XL-MS for protein conformation and interaction network analysis, highlights its unique advantages, discusses current technical challenges, and explores further development.

体内化学交联质谱（XL-MS）已成为一种强大的技术，用于高通量，蛋白质组范围内的分子内构象和活细胞中蛋白质复合物的分子间相互作用的定位。通过提供特定残基之间的距离约束，xml - ms能够表征近生理条件下的蛋白质构象和相互作用网络，极大地促进了生物大分子功能和调控机制的分析。从交联中获得的信息在系统层面上特别有价值，并且随着交联识别密度、距离约束精度和时空分辨率的提高，其价值将继续增加。近年来，交联剂设计、交联肽富集方法、质谱分析和人工智能辅助数据分析等方面的进展极大地扩展了体内xml - ms的能力。本文系统综述了体内xml - ms用于蛋白质构象和相互作用网络分析的最新进展，突出了其独特的优势，讨论了当前的技术挑战，并探讨了进一步的发展方向。

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引用次数: 0

Evolving advances of proximity labeling in capturing biomolecular interactions 接近标记在捕获生物分子相互作用中的发展进展

IF 6.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2025-09-11 DOI: 10.1016/j.cbpa.2025.102629

Ting Dang , Wenqing Shui

Proximity labeling (PL), with its capability to resolve spatiotemporal dynamics of biomolecular interactions, has become a pivotal technology for interrogating protein–protein interaction networks, subcellular proteomics, and intercellular communication. This review focuses on the breakthrough developments in PL from 2023 to 2025, highlighting three major frontiers: (1) catalytic system innovation, including the development of new enzymes, cascade reactions, and environment-responsive labeling systems, which collectively lead to increased spatiotemporal resolution and enhanced in vivo applicability; (2) new strategies to address endogenous targets, facilitating interactome mapping in native tissues and live animals; and (3) determination of the labeling radius for different PL tools using super-resolution imaging or DNA nanostructures. We also briefly discuss the desired innovation in the next-generation PL research.

近距离标记（PL）以其解决生物分子相互作用的时空动力学的能力，已成为询问蛋白质-蛋白质相互作用网络，亚细胞蛋白质组学和细胞间通讯的关键技术。本文综述了2023年至2025年PL的突破性进展，重点介绍了三个主要领域：(1)催化系统创新，包括新酶、级联反应和环境响应标记系统的开发，这些都提高了时空分辨率和体内适用性；(2)解决内源性靶点的新策略，促进本地组织和活体动物相互作用组的定位；(3)利用超分辨率成像或DNA纳米结构确定不同PL工具的标记半径。我们还简要讨论了下一代PL研究中需要的创新。

引用次数: 0

Mass spectrometry-based characterization of histone post-translational modification 基于质谱的组蛋白翻译后修饰表征

IF 6.9 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current Opinion in Chemical Biology

Pub Date : 2025-07-24 DOI: 10.1016/j.cbpa.2025.102622

Wensi Zhao , Jun Zhang , Kaifeng Chen , Jian Yuan , Linhui Zhai , Minjia Tan

Histone post-translational modifications (PTMs) play critical roles in regulating chromatin dynamics and gene expression. Increasing evidence demonstrates that the dysregulation of histone PTMs is closely associated with the pathogenesis of various diseases. Traditional methods for detecting histone PTMs, such as western blot (WB) and chromatin immunoprecipitation sequencing (ChIP-seq), are often limited by their dependence on specific antibodies and relatively low analytical throughput. Mass spectrometry (MS)-based proteomics offers a powerful and unbiased approach for comprehensive characterization of histone PTMs. This review focuses on the advanced development of MS-based strategies for characterizing histone PTMs. These strategies include histone extraction, enzymatic digestion, labeling, enrichment, and MS-based detection. These techniques not only enable comprehensive identification and quantitative analysis of classical modifications, such as acetylation and methylation, but also substantially facilitate the discovery of less-characterized histone PTMs, including succinylation, lactylation, crotonylation, and monoaminylation. Consequently, these findings significantly enhance the complexity of histone code. Collectively, MS-based approaches have profoundly advanced our understanding of histone PTM landscapes and their potential epigenetic regulatory mechanisms in both physiology and pathology contexts.

组蛋白翻译后修饰（PTMs）在调节染色质动力学和基因表达中起着至关重要的作用。越来越多的证据表明，组蛋白ptm的失调与多种疾病的发病密切相关。检测组蛋白ptm的传统方法，如western blot （WB）和染色质免疫沉淀测序（ChIP-seq），往往受其依赖于特异性抗体和相对较低的分析通量的限制。基于质谱（MS）的蛋白质组学为组蛋白ptm的全面表征提供了一种强大而公正的方法。本文综述了基于ms的组蛋白ptm表征策略的最新进展。这些策略包括组蛋白提取、酶消化、标记、富集和质谱检测。这些技术不仅能够对经典修饰（如乙酰化和甲基化）进行全面的鉴定和定量分析，而且还极大地促进了发现较少表征的组蛋白PTMs，包括琥珀酰化、乳酸化、巴豆酰化和单胺化。因此，这些发现显著提高了组蛋白编码的复杂性。总的来说，基于ms的方法深刻地推进了我们对组蛋白PTM景观及其在生理和病理背景下潜在的表观遗传调控机制的理解。

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引用次数: 0

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