ChemBioChem最新文献_第10页

How Clavulanic Acid Inhibits Serine β-Lactamases. 克拉维酸如何抑制丝氨酸 β-内酰胺酶？

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-25 DOI: 10.1002/cbic.202400280

Pauline Lang, Mariska de Munnik, Abraham Oluwole, Timothy Claridge, Carol Robinson, Jurgen Brem, Christopher Schofield

{"title":"How Clavulanic Acid Inhibits Serine β-Lactamases.","authors":"Pauline Lang, Mariska de Munnik, Abraham Oluwole, Timothy Claridge, Carol Robinson, Jurgen Brem, Christopher Schofield","doi":"10.1002/cbic.202400280","DOIUrl":"https://doi.org/10.1002/cbic.202400280","url":null,"abstract":"Clavulanic acid is a medicinally important inhibitor of serine β-lactamases (SBLs). We report studies on the mechanisms by which clavulanic acid inhibits representative Ambler class A (TEM-116), C (Escherichia coli AmpC), and D (OXA-10) SBLs using denaturing and non-denaturing mass spectrometry (MS). Similarly to observations with penam sulfones, most of the results support a mechanism involving acyl enzyme complex formation, followed by oxazolidine ring opening without efficient subsequent scaffold fragmentation (at pH 7.5). This observation contrasts with previous MS studies, which identified clavulanic acid scaffold fragmented species as the predominant SBL bound products. In all the SBLs studied here, fragmentation was promoted by acidic conditions, which are commonly used in LC‑MS analyses. Slow fragmentation was, however, observed under neutral conditions with TEM-116 on prolonged reaction with clavulanic acid. Although our results imply clavulanic acid scaffold fragmentation is likely not crucial for SBL inhibition in vivo, development of inhibitors that fragment to give stable covalent complexes is of interest.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141755935","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

pH sensitivity of YFPs is reduced upon AlphaRep binding: proof of concept in vitro and in living cells. 与 AlphaRep 结合后，YFP 的 pH 敏感性降低：体外和活细胞中的概念证明。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-24 DOI: 10.1002/cbic.202400287

Yasmina Bousmah, Magali Noiray, Hadrien Jalaber, Hélène Pasquier, Marie Béatrice Valerio-Lepiniec, Agathe Urvoas, Marie Erard

{"title":"pH sensitivity of YFPs is reduced upon AlphaRep binding: proof of concept in vitro and in living cells.","authors":"Yasmina Bousmah, Magali Noiray, Hadrien Jalaber, Hélène Pasquier, Marie Béatrice Valerio-Lepiniec, Agathe Urvoas, Marie Erard","doi":"10.1002/cbic.202400287","DOIUrl":"https://doi.org/10.1002/cbic.202400287","url":null,"abstract":"Yellow fluorescent proteins (YFPs) are commonly used in biology to track cellular processes, particularly as acceptors in experiments using the Förster Resonant Energy Transfer (FRET) phenomenon. However, their fluorescence intensity is strongly pH-dependent, limiting their utility in acidic environments. Here, we explore the pH sensitivity of YFPs upon binding with an artificial repeat protein (αRep) both in vitro and in living cells. We show that αRep binds to Citrine, with high affinity in the nanomolar range at physiological and acidic pHs, leading to increased thermal stability of the complex. Moreover, αRep binding reduces Citrine's pKa by 0.75 pH units, leading to a decreased sensitivity to pH fluctuations. This effect can be generalized to other YFPs as Venus and EYFP in vitro. An efficient binding of αRep to Citrine has also been observed in living cells both at pH 7.4 and pH 6. This interaction leads to reduced variations of Citrine fluorescence intensity in response to pH variations in cells. Overall, the study highlights the potential of αReps as a tool to modulate the pH sensitivity of YFPs, paving the way for future exploration of biological events in acidic environments by FRET in combination with a pH-insensitive cyan donor.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141750589","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

Engineering of a Malonyl-CoA Ligase for Production of Fluorinated Polyketide Extender Units. 工程化丙二酰-CoA 连接酶用于生产含氟多酮扩展单元。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-22 DOI: 10.1002/cbic.202400532

Thaddeus Q Paulsel, Gavin John Williams

引用次数: 0

Biosynthesis of Arcyriaflavin F from Streptomyces venezuelae ATCC 10712. 委内瑞拉链霉菌 ATCC 10712 的 Arcyriaflavin F 生物合成。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-22 DOI: 10.1002/cbic.202400357

Hung-En Lai, Agata Kennedy, Lewis Tanner, Emma Bartram, Soo Mei Chee, Paul Freemont, Simon Moore

引用次数: 0

Regioselective Deacetylation in Nucleosides and Derivatives. 核苷及其衍生物中的区域选择性去乙酰化。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-22 DOI: 10.1002/cbic.202400360

Charis Grabbe, Li Cai

引用次数: 0

OsO2 as the Contrast-Generating Chemical Species of Osmium-Stained Biological Tissues in Electron Microscopy. OsO2 作为电子显微镜下含锇生物组织的对比生成化学物。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-22 DOI: 10.1002/cbic.202400311

Ruiyu Li, Gregg Wildenberg, Kevin Boergens, Yingjie Yang, Kassandra Weber, Janek Rieger, Ashley Arcidiacono, Robert Klie, Narayanan Kasthuri, Sarah B King

{"title":"OsO2 as the Contrast-Generating Chemical Species of Osmium-Stained Biological Tissues in Electron Microscopy.","authors":"Ruiyu Li, Gregg Wildenberg, Kevin Boergens, Yingjie Yang, Kassandra Weber, Janek Rieger, Ashley Arcidiacono, Robert Klie, Narayanan Kasthuri, Sarah B King","doi":"10.1002/cbic.202400311","DOIUrl":"https://doi.org/10.1002/cbic.202400311","url":null,"abstract":"Electron imaging of biological samples stained with heavy metals has enabled visualization of subcellular structures critical in chemical-, structural-, and neuro-biology. In particular, osmium tetroxide OsO4 has been widely adopted for selective lipid imaging. Despite the ubiquity of its use, the osmium speciation in lipid membranes and the process for contrast generation in electron microscopy (EM) have continued to be open questions, limiting efforts to improve staining protocols and therefore high-resolution nanoscale imaging of biological samples. Following our recent success using photoemission electron microscopy (PEEM) to image mouse brain tissues with synaptic resolution, we have used PEEM to determine the nanoscale electronic structure of Os-stained biological samples. Os(IV), in the form of OsO2, generates nanoaggregates in lipid membranes, leading to a strong spatial variation in the electronic structure and electron density of states. OsO2 has a metallic electronic structure that drastically increases the electron density of states near the Fermi level. Depositing metallic OsO2 in lipid membranes allows for strongly enhanced EM signals and conductivity of biological materials. The identification of the chemical species and understanding of the membrane contrast mechanism of Os-stained biological specimens provides a new opportunity for the development of staining protocols for high-resolution, high-contrast EM imaging.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746907","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

Bio-electrocatalytic alkene reduction using ene-reductases with methyl viologen as electron mediator. 以甲基紫精为电子媒介，利用烯还原酶进行生物电催化烯还原。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-22 DOI: 10.1002/cbic.202400458

Zheng Wei, Tanja Knaus, Matteo Damian, Yuxin Liu, Cássia S Santana, Ning Yan, Gadi Rothenberg, Francesco Mutti

{"title":"Bio-electrocatalytic alkene reduction using ene-reductases with methyl viologen as electron mediator.","authors":"Zheng Wei, Tanja Knaus, Matteo Damian, Yuxin Liu, Cássia S Santana, Ning Yan, Gadi Rothenberg, Francesco Mutti","doi":"10.1002/cbic.202400458","DOIUrl":"https://doi.org/10.1002/cbic.202400458","url":null,"abstract":"Asymmetric hydrogenation of alkene moieties is important for the synthesis of chiral molecules, but achieving high stereoselectivity remains a challenge. Biocatalysis using ene-reductases (EReds) offers a viable solution. However, the need for NAD(P)H cofactors limits large-scale applications. Here, we explored an electrochemical alternative for recycling flavin-containing EReds using methyl viologen as a mediator. For this, we built a bio-electrocatalytic setup with an H-type glass reactor cell, proton exchange membrane, and carbon cloth electrode. Experimental results confirm the mediator's electrochemical reduction and enzymatic consumption. Optimization showed increased product concentration at longer reaction times with better reproducibility within 4-6 h. We tested two enzymes, Pentaerythritol Tetranitrate Reductase (PETNR) and the Thermostable Old Yellow Enzyme (TOYE), using different alkene substrates. TOYE showed higher productivity for the reduction of 2-cyclohexen-1-one (1.20 mM h-1), 2-methyl-2-cyclohexen-1-one (1.40 mM h-1) and 2-methyl-2-pentanal (0.40 mM h-1), with enantiomeric excesses ranging from 11% to 99%. PETNR outperformed TOYE in terms of enantioselectivity for the reduction of 2-methyl-2-pentanal (ee 59±7% (S)). Notably, TOYE achieved promising results also in reducing ketoisophorone, a challenging substrate, with similar enantiomeric excess compared to published values using NADH.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141746906","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

Research Progress of Cyanine-based Near-Infrared Fluorescent Probes for Biological Application. 用于生物应用的基于蓝素的近红外荧光探针的研究进展。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-22 DOI: 10.1002/cbic.202400467

Chusen Huang, Jigao Xuan, Jiajun Yu

引用次数: 0

Conformational Selection in Enzyme-Catalyzed Depolymerization of Bio-based Polyesters. 酶催化生物基聚酯解聚过程中的构象选择。

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-22 DOI: 10.1002/cbic.202400456

Ximena Lopez-Lorenzo, Ganapathy Ranjani, Per-Olof Syrén

{"title":"Conformational Selection in Enzyme-Catalyzed Depolymerization of Bio-based Polyesters.","authors":"Ximena Lopez-Lorenzo, Ganapathy Ranjani, Per-Olof Syrén","doi":"10.1002/cbic.202400456","DOIUrl":"https://doi.org/10.1002/cbic.202400456","url":null,"abstract":"Enzymatic degradation of polymers holds promise for advancing towards a bio-based economy. However, bulky polymers presents challenges in accessibility for biocatalysts, hindering depolymerization reactions. Beyond the impact of crystallinity, polymer chains can reside in different conformations affecting binding efficiency to the enzyme. We previously showed that the gauche and trans chain conformers associated with crystalline and amorphous regions of the synthetic polyethylene terephthalate (PET) display different affinity to PETase, thus affecting the depolymerization rate. However, structural-function relationships for biopolymers remain poorly understood in biocatalysis. In this study, we explored biodegradation of by-us previously synthesized bio-polyesters made from a rigid bicyclic chiral terpene-based diol and copolymerized with various renewable diesters. Herein, four of those polyesters spanning from semi-aromatic to aliphatic were subjected to enzymatic degradations in concert with induced-fit docking (IFD) analyses. Our findings demonstrate the importance of conformational selection in enzymatic depolymerization of biopolymers. A straight or twisted conformation of the polymer chain is crucial in biocatalytic degradation by showing different affinities to enzyme ground-state conformers. This work highlights the importance of considering the conformational match between the polymer and the enzyme to optimize the biocatalytic degradation efficiency of biopolymers, providing valuable insights for the development of sustainable bioprocesses.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141732881","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

Biochemical and Structural Consequences of NEDD8 Acetylation. NEDD8 乙酰化的生化和结构后果

IF 2.6 4区生物学

ChemBioChem Pub Date : 2024-07-18 DOI: 10.1002/cbic.202400478

Simon Maria Kienle, Tobias Schneider, Christine Bernecker, Janina Bracker, Andreas Marx, Michael Kovermann, Martin Scheffner, Katrin Stuber

引用次数: 0