ChemBioChem最新文献_第3页

Ion- and Temperature-Programmable Reconfiguration of Subcompartments in Synthetic Cells. 合成细胞中离子和温度可编程的子室重构。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.202500928

Zexi Xu, Petra Schwille

{"title":"Ion- and Temperature-Programmable Reconfiguration of Subcompartments in Synthetic Cells.","authors":"Zexi Xu, Petra Schwille","doi":"10.1002/cbic.202500928","DOIUrl":"https://doi.org/10.1002/cbic.202500928","url":null,"abstract":"Spatial reorganization of subcompartments is a hallmark of living cells, enabling coordinated metabolism and signaling. Achieving dynamic reconfiguration remains a major challenge in synthetic cell design. Although specific ions play fundamental physiological roles, their relevance in bottom-up synthetic biology has been underexplored. Particularly, magnesium ions (Mg2+), essential cofactors and signaling mediators in biological systems, regulate membrane interactions and molecular assemblies. Here, we present a purely Mg2+-mediated mechanism that enables reversible subcompartment assembly within synthetic cells. Mg2+ mediates adhesion between negatively charged giant unilamellar vesicles (GUVs), serving as synthetic cell chassis, and neutral large unilamellar vesicles (LUVs), mimicking subcompartments. Mg2+ coordination bridges opposing membranes form stable subcompartment layers. Lowering Mg2+ concentration, e.g., by chelation with EDTA, disrupts adhesion, whereas reintroduction of Mg2+ restores it, enabling dynamic and reversible control over membrane organization. The extent of LUV adhesion depends on membrane charge density, lipid phase state, and temperature. Phase separation allows spatially directed subcompartment to specific domains. Notably, adhesion is lost above the LUV phase transition temperature but re-established upon cooling, enabling temperature-programmed reassembly. Together, these findings define a minimal physicochemical framework for dynamic synthetic cell organization through physical stimuli and suggest a primitive lipid-ion mechanism underlying early membrane contact phenomena.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e202500928"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13108542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758060","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

How to Enhance the Applicability of Metal Ion Affinity-bound Biocatalysts? Comprehensive Overview and Case Study With a Phenylalanine Ammonia Lyase and an Amine Transaminase. 如何提高金属离子亲和结合生物催化剂的适用性？苯丙氨酸解氨酶和胺转氨酶的综合概述和案例研究。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.70346

Máté Laurinyecz, Bálint Alács, Zsófia Molnár, Laura Edit Barabás, Beáta G Vértessy, Csaba Paizs, László Poppe, Evelin Bell

{"title":"How to Enhance the Applicability of Metal Ion Affinity-bound Biocatalysts? Comprehensive Overview and Case Study With a Phenylalanine Ammonia Lyase and an Amine Transaminase.","authors":"Máté Laurinyecz, Bálint Alács, Zsófia Molnár, Laura Edit Barabás, Beáta G Vértessy, Csaba Paizs, László Poppe, Evelin Bell","doi":"10.1002/cbic.70346","DOIUrl":"https://doi.org/10.1002/cbic.70346","url":null,"abstract":"Selective metal ion affinity binding as a simple and renewable enzyme immobilization was investigated using the same affinity function on various supports. Phenylalanine ammonia-lyase from parsley (PcPAL) and an amine transaminase from Vibrio fluvialis (VfTA) with His-tag were used as model enzymes. Metal ion chelating groups on the surface of six enzyme carriers were created from the surface-alkylamino moieties by treatment with ethylenediaminetetraacetic dianhydride and subsequent complexation with cobalt(II) ions. Three porous polymer beads, two silica-based supports, and a silica-coated magnetic nanoparticle (MNP) were investigated as carriers. The most effective PcPAL biocatalyst forms were tested in kinetic resolution and ammonia addition reactions with substrates containing phenyl and thiophen-2-yl rings. In the selective ammonia addition reaction onto the (hetero)arylacrylates needing a harsh medium of a 6 M ammonia solution, the biocatalysts exhibited excellent stability and led to l-amino acids in high yield and excellent enantiomeric excess. The recharging of the MNP supports was investigated by five subsequent cycles of reactions-after elution with 5% diethylenetriamine and reloading with fresh PcPAL or VfTA-retaining over 80% of the relative activities until the third cycle. The repurposing of the supports was also investigated by changing one enzyme to the other on the MNP-immobilized metal ion affinity chromatography support.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70346"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758083","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

Multienzyme Platform for the Synthesis of UDP Sugars and Human Milk Oligosaccharides. 合成UDP糖和人乳低聚糖的多酶平台。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.202500716

Tuan Son Hoang, Fabian Lange, Sebastian Bruno Kleeberg, Lea Thomas, Nam-Hai Hoang, Udo Reichl, Thomas F T Rexer

{"title":"Multienzyme Platform for the Synthesis of UDP Sugars and Human Milk Oligosaccharides.","authors":"Tuan Son Hoang, Fabian Lange, Sebastian Bruno Kleeberg, Lea Thomas, Nam-Hai Hoang, Udo Reichl, Thomas F T Rexer","doi":"10.1002/cbic.202500716","DOIUrl":"https://doi.org/10.1002/cbic.202500716","url":null,"abstract":"Naturally occurring in breast milk, human milk oligosaccharides (HMOs) are of great interest as an ingredient for infant nutrition due to numerous associated health benefits. Current commercial production relies mainly on microbial fermentation, while enzymatic synthesis is used to produce milligram scales for scientific studies. Enzymatic synthesis using glycosyltransferases and nucleotide sugars is especially promising due to high reaction yields, but is limited by low activity of glycosyltransferases and the high cost of nucleotide sugars. This study presents a novel approach that uses a single engineered E. coli BL21(DE3) strain to simultaneously express six recombinant enzymes (UMPK, PPK3, GALK, NAHK, GALU, and PPA). This enables dual-nucleotide sugar synthesis through two integrated multienzyme cascades. The system uses cost-effective substrates, including uridine 5'-monophosphate (UMP), N-acetylglucosamine (GlcNAc), galactose (Gal), and ATP. In situ ATP regeneration is achieved through polyphosphate (PolyPn) breakdown. Comparative studies of three different expression strain configurations demonstrated that crude cell lysate could serve as an effective biocatalyst. This eliminates the need for expensive enzyme purification while maintaining high catalytic activity. Using crude cell lysate, conversion yields approaching 100% were obtained. Both UDP-GlcNAc and UDP-Gal were successfully purified using anion-exchange chromatography. Based on the UV spectrum, purities of 85-99% and recovery yields exceeding 90%, respectively, were achieved. The practical application of this system was demonstrated by the successful synthesis of two HMOs: Lacto-N-triose II (LNTII) and lacto-N-neotetraose (LNnT), which demonstrates an effective nucleotide sugar recycling in coupled enzymatic reactions and paves the way toward larger scale production.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e202500716"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13101873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758086","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

Exploring PadR Proteins for Artificial Enzyme Design. 探索PadR蛋白在人工酶设计中的应用

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.70308

Bart Brouwer, Andy-Mark W H Thunnissen, Henriette J Rozeboom, Gerard Roelfes

{"title":"Exploring PadR Proteins for Artificial Enzyme Design.","authors":"Bart Brouwer, Andy-Mark W H Thunnissen, Henriette J Rozeboom, Gerard Roelfes","doi":"10.1002/cbic.70308","DOIUrl":"https://doi.org/10.1002/cbic.70308","url":null,"abstract":"The development of artificial enzymes through incorporation of new-to-nature catalytic functionality into protein scaffolds has emerged as a powerful approach to expand the biocatalytic repertoire. Inspired by the success of Lactococcal multidrug resistance regulator (LmrR), a transcriptional regulator protein, whose unique scaffold has been used for the design of a range of artificial enzymes, we performed a bioinformatics study in an effort to expand the scope of protein scaffolds for artificial enzyme design with other LmrR-like proteins. LmrR belongs to the phenolic acid decarboxylase transcriptional regulator (PadR) subfamily 2 (PadR-s2) and exhibits an unusual open pore with promiscuous binding capabilities. Using genome mining and homology modeling, we identified six previously uncharacterized PadR-s2 proteins and experimentally evaluated them as protein scaffolds for the design of artificial Friedel-Crafts (FC) alkylases. Two of the candidates, Lactococcus fujiensis (LCf) PadR and Brachyspirahampsonii (Bh) PadR, could be applied in the iminium-promoted FC-alkylation using genetically incorporated noncanonical amino acids p-aminophenylalanine or 3-aminotyrosine as catalytic residues. Interestingly, contrary to homology models, AlphaFold predictions of the PadR-s2 candidates and X-ray crystallography of BhPadR and a variant incorporating 3-aminotyrosine revealed closed-pore structures. Our findings thus demonstrate that an open-pore structure like LmrR is not a prerequisite for designing artificial FC-alkylases and introduce two new PadR-s2 scaffolds for future application.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70308"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758129","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

Cy3-Conjugated Biocompatible Polymer Nanoparticles for Long-Term Mitochondrial Imaging. 用于长期线粒体成像的cy3共轭生物相容性聚合物纳米颗粒。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.70323

Souma Kawashima, Mitsuo Inui, Izumi Takaba, Haruka Taniguchi, Koji Nagahama

{"title":"Cy3-Conjugated Biocompatible Polymer Nanoparticles for Long-Term Mitochondrial Imaging.","authors":"Souma Kawashima, Mitsuo Inui, Izumi Takaba, Haruka Taniguchi, Koji Nagahama","doi":"10.1002/cbic.70323","DOIUrl":"10.1002/cbic.70323","url":null,"abstract":"The cyanine dye Cy3 has recently gained attention as a membrane potential-responsive, small-molecule mitochondrial imaging probe. However, the efficiency of Cy3 for mitochondrial imaging is relatively low, as diffusion of Cy3 leads to staining of the entire cell over time. This problem could be due to the passive diffusion-based, concentration-dependent uptake into cells and molecular diffusion inherent to small-molecule compounds. Therefore, we hypothesized that polymer chemistry approach could be applied to overcome these limitations. In this study, we designed modified dye in which biocompatible polymers were covalently attached to Cy3. This enabled control of intracellular dynamics that could not be achieved using Cy3 alone. Toward this objective, we synthesized a Cy3-modified amphiphilic dextran with phenylalanine ethyl ether side chains. The amphiphilic polymers self-assembled into nanoparticles. We then characterized the synthesized polymer in terms of intracellular uptake and the mitochondria translocation capacity of the nanoparticles using human skeletal muscle satellite cells. Our approach changed the cellular internalization process, resulting in increased cellular uptake efficiency, enhanced mitochondrial imaging capability, and improved mitochondrial retention over the long term. These nanoparticles, which can stain mitochondria regardless of cell type, have the potential to become a new type of mitochondrial imaging reagent.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70323"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715384","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

Activated Carbon-Supported Nanoscale Zero-Valent Iron for CO₂ Biomethanation: Stability, Transport in Porous Media, and Potential Reaction Pathways. 活性炭负载的纳米级零价铁用于二氧化碳生物甲烷化：稳定性，在多孔介质中的运输，和潜在的反应途径。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.202500808

Zhan-Hong Chen, Lei Zhou, Yu-Xuan Li, Jie Gao, Yi-Fan Liu, Shi-Zhong Yang, Bo-Zhong Mu

{"title":"Activated Carbon-Supported Nanoscale Zero-Valent Iron for CO2 Biomethanation: Stability, Transport in Porous Media, and Potential Reaction Pathways.","authors":"Zhan-Hong Chen, Lei Zhou, Yu-Xuan Li, Jie Gao, Yi-Fan Liu, Shi-Zhong Yang, Bo-Zhong Mu","doi":"10.1002/cbic.202500808","DOIUrl":"10.1002/cbic.202500808","url":null,"abstract":"Nanoscale zero-valent iron (nZVI) is an effective electron donor for the microbial reduction of CO2 to methane as an energy carrier. Nevertheless, the natural aggregation of nanostructures in aqueous porous media such as oil reservoirs is still a challenge in practical applications. To address this gap, iron-carbon nanocomposites (nZVI/AC) were synthesized using activated carbon (AC) as a support, and their dispersibility, transport behavior, and effects on the bioconversion of CO2 to methane were systematically investigated to explore their feasibility of serving as electron donors for the bioconversion of CO2 to methane in practical applications. Scanning electron microscopy (SEM) showed that AC effectively mitigated nZVI aggregation in aqueous solutions. Sedimentation and column experiments demonstrated that nZVI/AC exhibited improved colloidal stability and enhanced transport in porous media. In methanogenic microbial culture experiments, nZVI/AC was found to facilitate CO2 biomethanation compared with the no-addition control. Electrochemical, structural, and compositional analyses revealed that nZVI/AC possessed enhanced electron transfer capability and a higher dissolution rate, with siderite (FeCO3) identified as the primary reaction product. This study opens a new window for the design of iron-based composites with synergistic properties for CO2 biotransformation and the advancement of CO2 fixation and resource utilization in oil reservoirs.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e202500808"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727805","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

Investigation of the Linker-Length Preferences of Pantetheine Probes in the Cross-Linking Reactions Between Adenylation Enzymes and Carrier Proteins. Pantetheine探针在腺苷化酶与载体蛋白交联反应中的连接体长度偏好研究。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.70359

Iyo Arata, Kenji Nagata, Hakuto Miyoshi, Fumihiro Ishikawa, Taichi Chisuga, Toma Kashima, Genzoh Tanabe, Fumitaka Kudo, Tadashi Eguchi, Shinya Fushinobu, Akimasa Miyanaga

{"title":"Investigation of the Linker-Length Preferences of Pantetheine Probes in the Cross-Linking Reactions Between Adenylation Enzymes and Carrier Proteins.","authors":"Iyo Arata, Kenji Nagata, Hakuto Miyoshi, Fumihiro Ishikawa, Taichi Chisuga, Toma Kashima, Genzoh Tanabe, Fumitaka Kudo, Tadashi Eguchi, Shinya Fushinobu, Akimasa Miyanaga","doi":"10.1002/cbic.70359","DOIUrl":"10.1002/cbic.70359","url":null,"abstract":"Adenylation enzymes transfer acyl substrates selectively onto carrier proteins (CPs) in natural product biosynthesis. Despite the importance of adenylation enzyme-CP interactions, structural information on these transient complexes remains limited. Previously, we developed a pantetheine cross-linking probe (named C2Br), which contains an ethylenediamine linker with a reactive bromoacetamide group, and determined the structure of the cross-linked complex of the adenylation enzyme HitB with the CP HitD. Here, we investigated the linker-length effects of pantetheine probes in the cross-linking reactions of two adenylation enzymes, HitB and EntE, with CPs using probes with different diamine linkers, such as C2Br and C4Br, the latter containing a longer butanediamine linker moiety. Both adenylation enzymes formed cross-linked complexes with CPs irrespective of the probe used, but the reaction efficiencies depended on the linker length. Crystal structural analysis showed that the HitB-HitD interface interactions in the HitB-C4Br-HitD complex are essentially identical to those in the HitB-C2Br-HitD complex. In contrast, the diamine moieties of probes adopt different interaction modes, accounting for the observed variations in cross-linking efficiencies. A repertoire of pantetheine probes with varying linker lengths will facilitate structural studies on adenylation enzyme-CP interactions by enabling optimization for each adenylation enzyme.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70359"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727844","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

Quantifying Ligand-to-Protein Distances in Complex Environments Using Intermolecular ¹⁹F PRE NMR Spectroscopy. 利用分子间19F PRE核磁共振光谱定量复杂环境中配体到蛋白质的距离。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.70309

Yannick Werle, Martha-Louise Inderfurth, Christopher J Lang, Michael Kovermann

{"title":"Quantifying Ligand-to-Protein Distances in Complex Environments Using Intermolecular 19F PRE NMR Spectroscopy.","authors":"Yannick Werle, Martha-Louise Inderfurth, Christopher J Lang, Michael Kovermann","doi":"10.1002/cbic.70309","DOIUrl":"10.1002/cbic.70309","url":null,"abstract":"The determination of structural features is crucial to understand the interplay between structure and function of biomolecules and biomolecular complexes. In this context, nuclear magnetic resonance (NMR) spectroscopy provides experimental approaches, one of which is paramagnetic relaxation enhancement (PRE). Thus, placing a paramagnetic center and fluorine at strategic sites within (bio)molecules forming a complex enables the determination of distances through a straightforward, one-dimensionally guided NMR spectroscopic setup. Moreover, the almost absence of fluorine in biomolecules found in nature allows performing experimental work using cell-like or in cell conditions. Here, we made use of a single-cysteine mutant of Bacillus subtilis cold shock protein B (BsCspB) equipped with a paramagnetic spin label in complex with a fluorine-labeled variant of singly stranded DNA ligand dT4 to acquire intermolecular, 19F-based PREs. The distance between BsCspB and fluorine in dT4 has then been probed using three different experimental settings: in vitro, molecular crowding, and cell lysate conditions. Our data suggests that the intermolecular distance between the paramagnetically spin-labeled protein and the fluorine-labeled ligand does not change significantly using the three different conditions. This matches results regarding the conservation of binding affinities determined for this biomolecular complex using the three different conditions.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70309"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13089942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715318","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

Specific and Multi-Product Clade I and Clade IV Sesquiterpene Synthases Contribute to the Psilocybe cubensis Volatilome. 特异性和多产物分支I和分支IV倍半萜合成酶有助于裸盖菇挥发物。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.70318

Sebastian Schober, Lisa Dorfmann, Karl Walther, Felix Blei, Andrew R Chadeayne, Markus Gressler, Stefan Bartram, Sarah E O'Connor, Dirk Hoffmeister

{"title":"Specific and Multi-Product Clade I and Clade IV Sesquiterpene Synthases Contribute to the Psilocybe cubensis Volatilome.","authors":"Sebastian Schober, Lisa Dorfmann, Karl Walther, Felix Blei, Andrew R Chadeayne, Markus Gressler, Stefan Bartram, Sarah E O'Connor, Dirk Hoffmeister","doi":"10.1002/cbic.70318","DOIUrl":"10.1002/cbic.70318","url":null,"abstract":"Apart from the psychedelic psilocybin, the metabolite spectrum of Psilocybe \"magic mushrooms\" comprises sesquiterpenes, a class of natural products known to exhibit receptor-modulating bioactivities. However, the composition of the sesquiterpene profile has largely remained an open question. Here, we report the characterization of five Psilocybe cubensis sesquiterpene synthases, both in vitro using recombinantly produced enzymes and in vivo in Aspergillus niger. CubF is a clade I α-muurolol synthase. The investigated clade IV synthases were the near-identical CubG1 and CubG2 synthases, which catalyze mainly epi-isozizaene and β-duprezianene formation. Furthermore, CubH and CubI were identified as primarily making dauca-4(11),8-diene and β-barbatene, respectively. Gas chromatographic analyses of the headspaces of P. cubensis vegetative mycelium and fruiting bodies showed qualitative and quantitative differences, with sterpurene being among the major compounds in mycelium and dauca-4(11),8-diene in fruiting bodies. This fundamental knowledge of the P. cubensis terpenome may help distinguish the pharmacological effects of magic mushrooms versus pure psilocybin.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e70318"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727707","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

Molecular Dynamics Study of the Binding of Cationic, Anionic, and Neutral Luminescent Conjugated Ligands to the Alzheimer Folds of Aβ(1-42) and Tau Fibrils. 阳离子、阴离子和中性发光共轭配体与Aβ(1-42)和Tau原纤维阿尔茨海默折叠结合的分子动力学研究。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-04-28 DOI: 10.1002/cbic.202500902

Yogesh Todarwal, Mathieu Linares, Patrick Norman

{"title":"Molecular Dynamics Study of the Binding of Cationic, Anionic, and Neutral Luminescent Conjugated Ligands to the Alzheimer Folds of Aβ(1-42) and Tau Fibrils.","authors":"Yogesh Todarwal, Mathieu Linares, Patrick Norman","doi":"10.1002/cbic.202500902","DOIUrl":"https://doi.org/10.1002/cbic.202500902","url":null,"abstract":"Unbiased atomistic molecular dynamics simulations have been employed to examine the binding interactions between amyloid fibrils (Aβ(1-42) and tau) with various ligands: anionic pFTAA, qFTAA-CN, neutral HS-276, and cationic bTVBT4. The ligand-fibril interactions were analyzed in a two-step approach. First, an analysis of the spatial distributions of the ligands around the amyloid fibril protofilaments was carried out to identify prospective binding sites. Second, the associated ligand-fibril binding energies at these sites were determined using umbrella sampling. The results reveal that pFTAA and qFTAA-CN share common binding sites in both Aβ(1-42) and tau fibrils. Ligands bTVBT4 and HS-276, on the other hand, are found to have different binding sites in Aβ(1-42) but share the same site in tau fibrils. An analysis of the spatial distributions of all ligand-fibril pair combinations under comparable conditions shows the lowest densities when bTVBT4 interacts with Aβ(1-42) and HS-276 with the tau fibril. These findings are corroborated by fluorescence costaining experiments, in which bTVBT4 and HS-276 show no correlation with Aβ-specific and tau-specific antibody markers, respectively. Further structural analysis reveals significant changes in the conformations of all ligands upon binding to the proteins compared to their conformations in aqueous solution. The binding of the anionic ligands (multiple localized negative charges) to fibrils is primarily driven by Coulombic forces, whereas the binding of the neutral HS-276 and cationic bTVBT4 (single delocalized positive charge) is governed by Lennard-Jones interactions. This highlights the influence of charges on binding, providing insights for the design of future ligands targeting Aβ(1-42) and tau fibrils.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 8","pages":"e202500902"},"PeriodicalIF":2.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147758138","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