ChemBioChem最新文献_第10页

S-Adenosyl-d-Methionine as a Non-Physiological Substrate for a Wide Range of SAM-Dependent Enzymes s -腺苷-d-蛋氨酸作为多种sam依赖酶的非生理底物。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-26 DOI: 10.1002/cbic.70467

Philipp Germer, Lukas Gericke, Lars-Hendrik Koeppl, Ziruo Zou, Emely Jockmann, Marco Kuge, Katrin Zoller, Hannah Herrmann, Ronja Fuderer, Michael K. F. Mohr, Agnes Bartels, Göksu Oral, Peer Lukat, Gunhild Layer, Michael Müller, Wulf Blankenfeldt, Lena Barra, Jennifer N. Andexer

{"title":"S-Adenosyl-d-Methionine as a Non-Physiological Substrate for a Wide Range of SAM-Dependent Enzymes","authors":"Philipp Germer, Lukas Gericke, Lars-Hendrik Koeppl, Ziruo Zou, Emely Jockmann, Marco Kuge, Katrin Zoller, Hannah Herrmann, Ronja Fuderer, Michael K. F. Mohr, Agnes Bartels, Göksu Oral, Peer Lukat, Gunhild Layer, Michael Müller, Wulf Blankenfeldt, Lena Barra, Jennifer N. Andexer","doi":"10.1002/cbic.70467","DOIUrl":"10.1002/cbic.70467","url":null,"abstract":"The ability of SAM-dependent enzymes to accept S-adenosyl-d-methionine [d-SAM, (SS,RCα)-SAM] instead of the native cofactor S-adenosyl-l-methionine [l-SAM, (SS,SCα)-SAM] remains largely unexplored. Challenging the stereochemical preference of SAM-dependent enzymes, we investigated the ability of different enzyme classes to accept d-SAM. Contrary to common assumptions, the tested N- and O-methyltransferases (MTs), as well as one of the examined C-MTs accepted d-SAM. Docking studies suggest that acceptance of d-SAM by C-MTs may be influenced by the angle between the transferable methyl group of SAM and the nucleophilic carbon of the substrate, along with enzyme and substrate flexibility. In addition to conventional MTs, the radical SAM glutamine C-MT QCMT showed low but detectable methylation activity with d-SAM. Furthermore, the azetidine-2-carboxylic acid synthase AzeJ not only uses d-SAM but also incorporates the stereocentre of d-methionine into the cyclic amino acid product. The pyridoxal 5ʹ-phosphate (PLP)-dependent enzyme 1-aminocyclopropyl-1-carboxylic acid synthase (ACCS) also showed detectable turnover with d-SAM. These findings broaden the understanding of enzyme stereoselectivity, provide an overview of d-SAM-utilising enzymes, and identify the first enzyme systems that may serve as starting points for engineering efforts aimed at shifting cofactor preference towards d-SAM.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Honeydew: A Fluorescent Aptamer for Low-Cost Azo Food Dyes 蜜露：一种低成本偶氮食品染料的荧光适体。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-26 DOI: 10.1002/cbic.70471

Joseph M. Heili, Paul H. Mroch, Tanner G. Hoog, Orion M. Venero, Grace M. Gustafson, Katarzyna P. Adamala, Aaron E. Engelhart

{"title":"Honeydew: A Fluorescent Aptamer for Low-Cost Azo Food Dyes","authors":"Joseph M. Heili, Paul H. Mroch, Tanner G. Hoog, Orion M. Venero, Grace M. Gustafson, Katarzyna P. Adamala, Aaron E. Engelhart","doi":"10.1002/cbic.70471","DOIUrl":"10.1002/cbic.70471","url":null,"abstract":"Light-up RNA aptamers that bind nonfluorescent dyes and conditionally activate their fluorescence are powerful tools for RNA imaging and biomolecular sensing. A barrier to widespread adoption of this technology is a reliance on bespoke dyes prepared by labor-intensive or costly custom synthesis. Here, we demonstrate that azo dyes—abundant, ultra-low-cost (<$1/g), and low-toxicity molecules widely used in the food and textile industries—can serve as conditionally fluorescent aptamer ligands. We selected aptamers against tartrazine, a ubiquitous azo food dye, and identified a fluorescence-activating aptamer, which we term Honeydew. We show that Honeydew bound to tartrazine enables real-time sensing and imaging of model synthetic cells. Additionally, Honeydew selectively activates conditional fluorescence of several other azo dyes, underscoring the untapped potential of this broad dye class. By repurposing ubiquitous industrial dyes, Honeydew is a first-in-class fluorogenic azo dye aptamer that provides a highly accessible platform for imaging and sensing applications.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Synthesis, Characterization, and Fluorescence Application of Indole-Based Isofunctional NAD+ Analogs 吲哚基同功能NAD+类似物的合成、表征及荧光应用。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-26 DOI: 10.1002/cbic.202500797

Danqi Li, Bo Zhuang, Ran-ran Feng, Feng Gai

{"title":"Synthesis, Characterization, and Fluorescence Application of Indole-Based Isofunctional NAD+ Analogs","authors":"Danqi Li, Bo Zhuang, Ran-ran Feng, Feng Gai","doi":"10.1002/cbic.202500797","DOIUrl":"10.1002/cbic.202500797","url":null,"abstract":"Nicotinamide adenine dinucleotide (NAD+) participates in many key cellular processes. However, as NAD+ is essentially nonfluorescent, studying its reactions via fluorescence-based methods is challenging. In this regard, we synthesize two NAD+ analogs: 4CNI-NAD+ and 4CN7AI-NAD+, where the adenine moiety of NAD+ is replaced by the highly fluorescent 4-cyanoindole (4CNI) and 4-cyano-7-azaindole (4CN7AI) groups, respectively. Both 4CNI-NAD+ and 4CN7AI-NAD+ exhibit similar biochemical properties to native NAD+ and can be recognized as cofactors or substrates by enzymes such as alcohol dehydrogenase (ADH) and NADase, where the reaction rates of 4CN7AI-NAD+ are comparable to native NAD+. The conversion of 4CNI-NAD+ and 4CN7AI-NAD+ to their corresponding reduced form (i.e., NADH) leads to a decrease in fluorescence intensity, and cleavage of the nicotinamide moiety significantly enhances the fluorescence. These photophysical properties are largely regulated by the interactions between the nicotinamide and cyanoindole groups, as demonstrated by molecular simulations and quantum chemical calculations. Taken together, these two analogs can be used to monitor NAD+-dependent enzymatic reactions, in particular, those involving NAD+/NADH hydrolysis, via dynamic changes in the absorption and fluorescence spectra, expanding the toolkit for the study of physiological NAD+-related processes.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148589711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Characterization of a Purine Nucleoside Phosphorylase From Colwellia sp. WH041 for Multienzyme Synthesis of Nucleoside Analogs 用于多酶合成核苷类似物的一种来自Colwellia sp. WH041的嘌呤核苷磷酸化酶的表征

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-24 DOI: 10.1002/cbic.70476

Shirong Wang, Yu Zhang, Fan Yang, Fuxue Chen, Xingcheng Shao, Gaofei Liu, Bin Wu

{"title":"Characterization of a Purine Nucleoside Phosphorylase From Colwellia sp. WH041 for Multienzyme Synthesis of Nucleoside Analogs","authors":"Shirong Wang, Yu Zhang, Fan Yang, Fuxue Chen, Xingcheng Shao, Gaofei Liu, Bin Wu","doi":"10.1002/cbic.70476","DOIUrl":"https://doi.org/10.1002/cbic.70476","url":null,"abstract":"Multienzyme cascades provide an efficient biocatalytic strategy for synthesizing nucleoside analogs from simple sugar donors and nucleobases. In pentose-to-nucleoside cascades, purine nucleoside phosphorylase (PNP) catalyzes the terminal N-glycosylation step and strongly influences product formation and substrate scope. Here, seven putative PNP homologs from microorganisms isolated from low-temperature environments were evaluated under EcRK-EcPPM-PNP cascade conditions. A PNP from Colwellia sp. WH041, designated ColPNP, showed the highest arabinofuranosylation activity and was selected for further characterization. ColPNP displayed optimal activity at 45 °C and exhibited a 12.7-fold higher catalytic efficiency than Escherichia coli PNP at the same temperature. Molecular dynamics simulations supported the favorable catalytic performance of ColPNP under moderate-temperature conditions. After optimization of the EcRK-EcPPM-ColPNP cascade, vidarabine conversion reached 58.2% within 12 h. The optimized system was further applied to synthesize diverse nucleoside analogs with conversions of 45.8%–89.8%, and guanosine analogs were obtained through sequential EcADA-mediated deamination. This study expands the PNP toolbox and demonstrates ColPNP as an efficient module for enzymatic nucleoside analog synthesis.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148565138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Employing Nanotechnology to Enhance Ethanol Production in Two Synechococcus elongatus Strains 利用纳米技术提高两株长聚球菌的乙醇产量

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-24 DOI: 10.1002/cbic.70480

Alexandra M. Schirmacher, David A. Russo, Alexandra C. U. Furch, Julie A. Z. Zedler

{"title":"Employing Nanotechnology to Enhance Ethanol Production in Two Synechococcus elongatus Strains","authors":"Alexandra M. Schirmacher, David A. Russo, Alexandra C. U. Furch, Julie A. Z. Zedler","doi":"10.1002/cbic.70480","DOIUrl":"https://doi.org/10.1002/cbic.70480","url":null,"abstract":"Cyanobacteria have emerged as promising photosynthetic cell factories. However, low product yields remain a bottleneck to industrial exploitation. Here, we use bacterial microcompartment technology to improve product titres using ethanol biosynthesis as the model pathway. Two strategies compared to unmodified enzyme production were tested: first, targeting enzymes to nanofilaments by fusion with encapsulation peptides (EPs) which form non-covalent interactions with the filaments. Second, the enzyme-EP fusions were used in the absence of nanofilaments, as EPs tend to form soluble aggregates. Both approaches were tested in Synechococcus elongatus PCC 7942 and the fast-growing Synechococcus elongatus UTEX 2973 to validate if fast growth is additionally beneficial for bioproduction. The EPs had the most dramatic effect on enzyme levels and ethanol production leading to an increase in titres of up to 84 times in comparison to the unmodified enzymes. While Se7942 exhibited higher titres per cell, titres were the highest in Se2973 due to a 79% increase in final cell density. Ultimately, the best strategy (enzyme-EP fusion in the absence of PduA*) led to 1.31 g L−1 of ethanol in 6 days. This work demonstrates that nanotechnology-based strategies can aid cyanobacterial bioproduction and will serve as a blueprint for future engineering efforts.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70480","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Continuous and Divergent Biotransformation of β-Ketoesters Into Enantiomerically Pure β-Hydroxyacids or Their Oligomers Through a Telescoped Multienzyme Cascade 通过伸缩多酶级联将β-酮酯连续和分散转化为对映体纯β-羟基酸或其低聚物

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-24 DOI: 10.1002/cbic.70474

Giulio Pota, Daniel Andrés-Sanz, Ainhoa Maiz-Iginitz, Mariana A. Armendáriz-Ruiz, Haritz Sardon, Giuseppe Vitiello, Valeria Califano, Aniello Costantini, Fernando López-Gallego

{"title":"Continuous and Divergent Biotransformation of β-Ketoesters Into Enantiomerically Pure β-Hydroxyacids or Their Oligomers Through a Telescoped Multienzyme Cascade","authors":"Giulio Pota, Daniel Andrés-Sanz, Ainhoa Maiz-Iginitz, Mariana A. Armendáriz-Ruiz, Haritz Sardon, Giuseppe Vitiello, Valeria Califano, Aniello Costantini, Fernando López-Gallego","doi":"10.1002/cbic.70474","DOIUrl":"https://doi.org/10.1002/cbic.70474","url":null,"abstract":"Efficient, selective, and sustainable synthetic platforms are increasingly important in modern chemical manufacturing, yet chemical flexibility often remains limited. In this study, we develop a modular biocatalytic system for the divergent and continuous transformation of ethyl acetoacetate (EAA) into either enantiomerically pure (R)-3-hydroxybutyric acid ((R)-3HBA) or oligomers of (R)-poly(3-hydroxybutyrate) (PHB). The cascade combines two telescoped packed-bed reactors containing an immobilized, self-sufficient Lactobacillus kefir ketoreductase (LkKRED) and commercial immobilized Candida antarctica lipase B (N435). By simply tuning the reaction conditions, the system selectively directs the substrate toward either product. Under aqueous conditions, it achieves quantitative conversion to (R)-3HBA with >99% enantiomeric excess and maintains excellent stability over 7 days of continuous operation. It also reaches a maximum space–time yield of 105 g L−1 h−1, which is 33 times higher than the volumetric productivity of the sequential two-pot process. Under anhydrous conditions, the same setup promotes polycondensation into PHB oligomers, as confirmed by matrix-assisted laser desorption/ionization time-of-flight analysis. Overall, this platform combines productivity, stereoselectivity, and flexibility for the integrated synthesis of chiral building blocks or oligomers.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148576106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Reconsidering Molecular Docking Practices in Aptamer Research 重新思考适体研究中的分子对接实践

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-24 DOI: 10.1002/cbic.70481

Yachen Xie, Juewen Liu

{"title":"Reconsidering Molecular Docking Practices in Aptamer Research","authors":"Yachen Xie, Juewen Liu","doi":"10.1002/cbic.70481","DOIUrl":"https://doi.org/10.1002/cbic.70481","url":null,"abstract":"Molecular docking is increasingly used to infer aptamer–target interactions, yet most studies rely on computationally predicted aptamer structures rather than experimentally determined ones. Using a benchmark set of aptamers with known high-resolution structures, we show that commonly used modeling approaches, including RNAComposer and AlphaFold3, fail to reliably reproduce aptamer conformations, particularly at the binding sites critical for molecular recognition. Key limitations include the use of A-form RNA models to represent B-form DNA structures, the prediction of ligand-free rather than ligand-bound conformations, and the scarcity of experimentally determined aptamer structures for training machine-learning models. Using the theophylline aptamer, for which high-resolution structures are available in both DNA and RNA forms, we systematically evaluated each step of the standard docking workflow. We found that structure-prediction errors generate incorrect binding pockets, docking scores fail to distinguish theophylline from caffeine despite a 250,000-fold difference in affinity, and molecular dynamics simulations do not overcome these shortcomings. Together, these results reveal fundamental weaknesses in current aptamer docking workflows and caution against using docking-derived models to infer binding mechanisms in the absence of experimental structural data.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70481","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148565140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

A Highly Thermostable Heme–G-Quadruplex DNAzyme: Structural Integrity and Catalytic Function Under Elevated-Temperature Aqueous Conditions 高度热稳定的血红素- g -四联DNAzyme：结构完整性和在高温水条件下的催化功能

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-24 DOI: 10.1002/cbic.70482

Daiki Fukasawa, Ryo Karita, Yuri Shokaku, China Okamoto, Yasuhiko Yamamoto, Atsuya Momotake

引用次数: 0

Hydrogel Chemistry in Expansion Microscopy: From Polyacrylamide to Next-Generation Swellable Polymers 膨胀显微镜中的水凝胶化学：从聚丙烯酰胺到下一代可膨胀聚合物

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-24 DOI: 10.1002/cbic.70465

Min Hou, Min Tang, WeiJin Peng, Ang Li

{"title":"Hydrogel Chemistry in Expansion Microscopy: From Polyacrylamide to Next-Generation Swellable Polymers","authors":"Min Hou, Min Tang, WeiJin Peng, Ang Li","doi":"10.1002/cbic.70465","DOIUrl":"https://doi.org/10.1002/cbic.70465","url":null,"abstract":"Expansion microscopy (ExM) is a transformative biological imaging approach that achieves nanoscale resolution on conventional diffraction-limited microscopes by physically expanding specimens embedded in swellable hydrogels. Since its introduction in 2015, the hydrogel chemistry underpinning ExM has evolved considerably, progressing from the original sodium polyacrylate/polyacrylamide (PAAm) formulations toward advanced polymer architectures that address persistent limitations in expansion factor, isotropy, and structural fidelity. This review comprehensively analyzes the hydrogel chemistry landscape in ExM, tracing the progression from classical polyacrylamide-based gels through modified acrylamide formulations and high-expansion dimethylacrylamide (DMAA) systems to next-generation click-chemistry-based tetra-gel platforms. We critically examine the polymerization mechanisms, monomer composition, crosslinker design, and anchoring strategies governing gel performance, and evaluate how these parameters influence expansion factor, mechanical integrity, and biomolecular spatial fidelity. Emerging approaches, including single-shot 20-fold expansion protocols and microwave-accelerated workflows, are discussed in the context of their underlying polymer chemistry. By synthesizing findings from the primary literature through 2025, this review aims to guide researchers in selecting and optimizing hydrogel systems for specific imaging applications and to identify promising directions for future polymer innovation in ExM.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 14","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148565152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

ChemBioParis 2025: Approaching Biology Through Chemistry in the City of Light 化学生物巴黎2025：在光之城通过化学接近生物学

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-07-24 DOI: 10.1002/cbic.70470

Marc Panosetti, Manon Sturbaut, Marie Auvray, Lisa Gourdon-Grunenwaldt, Lina El Hajji

引用次数: 0