ACS Publications最新文献

{"title":"Synthesis and Antimicrobial Specificities of Halogenated Tryptophan-Containing Nisin Variants.","authors":"Chenhui Wang, Sanne Tervoort, Oscar P Kuipers, Jaap Broos","doi":"10.1021/acschembio.5c00632","DOIUrl":"https://doi.org/10.1021/acschembio.5c00632","url":null,"abstract":"<p><p>Antimicrobial peptides, and in particular ribosomally produced and post-translationally modified peptides (RiPPs), are a potentially important class of candidate antibiotics for combating multidrug-resistant bacteria. Introduction of a halogenated Trp residue into a RiPP can possibly enhance antimicrobial efficacy and alter specificity, but this modification has hardly been explored. This study employs an efficient expression system utilizing a tryptophan auxotrophic <i>Lactococcus lactis</i> strain to biosynthetically and efficiently incorporate halogenated tryptophan analogues, namely 5-fluoro-tryptophan (5FW), 5-chloro-tryptophan (5CW), 5-bromo-tryptophan (5BW), as well as 5-methyl-tryptophan (5MW) at position 1 of I1W nisin A. Wild-type nisin and Trp-containing I1W nisin show a high and broad activity against four tested pathogens. However, the activity spectrum of the three different halogen atom containing nisin variants became more strain specific, as both increased and decreased activities were measured against the four tested pathogens. No trend between the chemical properties of the halogen atom (e.g., electronegativity, size) and the bioactivity of the nisin variants toward each of the four pathogens could be detected, suggesting strain specific antimicrobial activity mechanisms. These findings demonstrate that halogenated tryptophan analogues can be successfully incorporated into a bioactive RiPP produced by an auxotrophic <i>L. lactis</i> strain and underscore the utility of peptide halogenation for discovering novel antimicrobial agents with tailored pathogen specificity.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051387","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}

{"title":"Photocatalytic Conversion of <i>p</i>-Xylene into <i>p</i>-Tolualdehyde with Near 100% Selectivity via a Novel Hydroxyl Radical-Mediated Oxygenation Route.","authors":"Yuan Lu, Seungho Yu, Jie Jin, Zhonghao Wang, Tae-Kyung Liu, Ki Chul Kim, Kan Zhang, Jong Hyeok Park","doi":"10.1021/jacs.5c10960","DOIUrl":"https://doi.org/10.1021/jacs.5c10960","url":null,"abstract":"<p><p><i>p</i>-Tolualdehyde (<i>p</i>-TALD) is an important chemical intermediate that is widely used in the fragrance and pharmaceutical industries. Photocatalytic upgrading of <i>p</i>-xylene into <i>p</i>-TALD is a promising route but suffers from undesired overoxidation via conventional molecular oxygen-mediated oxygenation due to difficulties associated with desorbing the products from catalyst active sites. In this work, a novel photocatalytic hydroxyl radical (·OH)-mediated oxygenation route is reported for <i>p</i>-xylene to <i>p</i>-TALD conversion, in which the ·OH serves as oxygen donors to generate intermediates containing hydroxyl functional groups that readily form hydrogen bonds with surface hydroxyl groups of the P25 photocatalyst. This hydrogen bonding interaction effectively regulates the adsorption-desorption behavior of intermediates and products, thereby significantly enhancing the selectivity toward <i>p</i>-TALD from 45.25% to nearly 100%, delivering an impressive <i>p</i>-TALD production rate of 3568.8 μmol g^-1 h^-1. This work provides a promising strategy for overcoming the common issue of severe overoxidation encountered during photocatalytic upgrading of organic substrates.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme-Activated Sugar-Coated Bifunctional Degraders.","authors":"Qian Zhu, Gerhard Fischer, Steven S Cheng, N Connor Payne, Daniel Peter, Alison C Mody, Silvia Arce-Solano, Dacheng Shen, Zhi Lin, Ralph Mazitschek, Dirk Kessler, Christina M Woo","doi":"10.1021/jacs.5c09843","DOIUrl":"https://doi.org/10.1021/jacs.5c09843","url":null,"abstract":"<p><p>Targeted protein degradation with compounds like proteolysis targeting chimeras (PROTACs) directs disease-associated proteins to the E3 ligase ubiquitin-proteasome system for removal. However, commonly employed E3 ligases such as cereblon (CRBN) are broadly expressed. To metabolically gate PROTAC activity, we developed an enzymatic activation strategy by integrating an O-GlcNAc modification to the cyclimids, ligands derived from the natural motifs recognized by CRBN. These sugar-coated PROTACs (SCPs) were designed using structural analyses of representative cyclimid degraders complexed with CRBN and target protein BRD4. We found that glycosylation of the cyclimid reduced CRBN binding and complex formation with BRD4 until enzymatic removal of the O-GlcNAc moiety by O-GlcNAcase (OGA). The requirement for enzymatic activation is demonstrated by <i>in vitro</i> biochemical binding, cellular degradation, and cell viability assays in engineered and native cell lines. O-GlcNAc is thus an effective mechanism to gate targeted protein degradation modalities that motivates the development of similar strategies to enhance selectivity with other protein modifications.</p>","PeriodicalId":49,"journal":{"name":"Journal of the American Chemical Society","volume":" ","pages":""},"PeriodicalIF":15.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure of Bovine Glycine <i>N</i>-Acyltransferase Clarifies Its Catalytic Mechanism.","authors":"Ana C Ebrecht, Christoffel P S Badenhorst, Uwe T Bornscheuer, Randy J Read, Diederik J Opperman, Alberdina A van Dijk","doi":"10.1021/acs.biochem.5c00315","DOIUrl":"https://doi.org/10.1021/acs.biochem.5c00315","url":null,"abstract":"<p><p>Glycine <i>N</i>-acyltransferase (GLYAT; EC 2.3.1.13, Accession ID: AAI12537) is a key enzyme in mammalian homeostasis that has been linked to several pathologies in humans, including cancer. Here we report the first crystal structure of a member of the GLYAT family, both in the apo form as well as bound to benzoyl-CoA. Binding of glycine could be inferred from an acetate molecule from the crystallization solution. A detailed analysis of its structure and the effects of mutations of key residues helped elucidate the catalytic mechanism, showing a general base-catalyzed reaction driven by a potential low-barrier hydrogen bond (LBHB) formed between the catalytic Glu-His dyad. This work will aid further studies of GLYAT and other members of the family.</p>","PeriodicalId":28,"journal":{"name":"Biochemistry Biochemistry","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Larval Ascariasis Triggers Unresolved Anemia, Persistent Inflammation, and Chronic Pulmonary Disease after Single and Reinfection in a Dose-Dependent Manner in Mice.","authors":"Jorge Lucas Nascimento Souza, Chiara Cássia Oliveira Amorim, Camila de Almeida Lopes, Flaviane Vieira-Santos, Ana Rafaela Antunes-Porto, Fernanda Rezende Souza, Evelyn Ane Oliveira, Thaynan Cunha Vieira, Lucas Kraemer, Marcelo Eduardo Cardozo, Ramayana Morais de Medeiros Brito, Luisa Mourão Dias Magalhães, Geovanni Dantas Cassali, Ricardo Toshio Fujiwara, Remo Castro Russo, Lilian Lacerda Bueno","doi":"10.1021/acsinfecdis.5c00477","DOIUrl":"https://doi.org/10.1021/acsinfecdis.5c00477","url":null,"abstract":"<p><p>Although different studies have investigated the pathophysiological aspects of ascariasis using experimental models, the long-term effects following the peak of larval migration in the lungs remain poorly understood, especially in different doses of infection, such as those that mimic better the natural infection scenario. In this study, we evaluated the impact of different infection doses (250, 1250, and 2500 eggs) and amount of exposure (single vs reinfection) on the host's immune response over an extended period. Our findings demonstrate that even the lowest dose (250 eggs) can induce persistent, though less severe, pathological damages compared to higher doses. These include anemia resulting from alveolar hemorrhage and the development of chronic pulmonary disease. Notably, while lower doses elicit a milder immune response, clinical manifestations tend to appear later, indicating a delayed pathological impact. Importantly, inflammatory infiltrates and altered cytokine levels (including Th1/Th2/Th17) were still observed in the lungs more than 100 days postinfection, even after larval clearance. The humoral immune response against <i>Ascaris suum</i> remained active for at least 100 days postinfection, with the potential for longer persistence. Notably, even with lower doses, only two exposures were sufficient to trigger an immune pattern similar to that observed at higher doses. These findings highlight the need for further investigation into the chronic inflammatory effects of <i>Ascaris</i> infection, including its impact on distant organs and its potential contribution to the development of noncommunicable diseases and comorbidities. A better understanding of these mechanisms is essential for developing improved strategies to control ascariasis in endemic areas.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Coronavirus-229E Hijacks Key Host-Cell RNA-Processing Complexes for Replication.","authors":"Snigdha Sarkar, Song Feng, Hugh D Mitchell, Madelyn R Berger, Tong Zhang, Isaac K Attah, Chelsea M Hutchinson-Bunch, Victoria N Prozapas, Kristin Engbrecht, Stephanie King, Amy C Sims, John T Melchior","doi":"10.1021/acs.jproteome.5c00400","DOIUrl":"https://doi.org/10.1021/acs.jproteome.5c00400","url":null,"abstract":"<p><p>The recent rise in zoonotic coronavirus outbreaks underscores the urgency to understand virus-host interactions to develop potent antiviral therapeutics. Systems biology approaches, particularly proteomics, have been invaluable in providing a global overview of such interactions. However, these conventional approaches rely on measuring protein abundance changes that do not capture all molecular changes associated with altered regulatory pathways. In this study, we employed a high-throughput structural proteomics approach called limited proteolysis-based mass spectrometry (LiP-MS) to capture protein conformational changes, which we demonstrate are better proxies for functional alterations. We applied this tool to profile the molecular landscape of different human lung cells following human coronavirus-229E (HCoV-229E) infection. We found that HCoV-229E uses a multipronged approach to hijack key RNA-processing pathways and assemblies as part of a host-shutoff strategy to achieve effective replication. We confirm our results with structural data derived from changes in the assemblies after infection. We go on to show that modulation of two of these assemblies, the Nop56-associated pre-rRNA complex and the spliceosome C-complex, can attenuate HCoV-229E replication, indicating that we have identified viable host-cell therapeutic targets with potential to provide broad efficacy against coronavirus infection.</p>","PeriodicalId":48,"journal":{"name":"Journal of Proteome Research","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038754","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}

{"title":"Dual Action Nitric Oxide-Releasing Polydimethylsiloxane Sponge: Preventing Infection in Needleless Connectors.","authors":"Adam Brooks Goodman, Manjyot Kaur Chug, Natalie Crutchfield, Mark Garren, Hitesh Handa, Elizabeth J Brisbois","doi":"10.1021/acsabm.5c01100","DOIUrl":"https://doi.org/10.1021/acsabm.5c01100","url":null,"abstract":"<p><p>Catheter-related bloodstream infections (CRBSIs) are a prevalent concern, often resulting from suboptimal disinfection practices of needleless connectors. Although alcohol-based disinfectants have demonstrated efficacy, there is growing concern about developing microbial resistance. Similar to antibiotics in recent decades, microbes have the potential to develop resistance to these alcohol-based therapies. Therefore, this study delves into the antimicrobial potential of nitric oxide (NO), an endogenous gas molecule with broad-spectrum antimicrobial properties, in combination with the widely used disinfectant 70% isopropanol (IPA). Due to its short half-life, NO presents minimal risk of microbial resistance development. By incorporating <i>S</i>-nitroso-<i>N</i>-acetylpenicillamine (SNAP), a synthetic NO donor, into hydrophilic-modified polydimethylsiloxane (PDMS-PEO) sponges using 70% IPA, the sponge functions as an antimicrobial reservoir, effectively sterilizing the hub region of needleless connectors. Formulation-dependent effects on sponge porosity were observed, affecting compressive strength, absorption capacity, SNAP retention, and NO release kinetics. Up to 30% variation in sponge porosity coincided with a tunable compressive modulus, increased absorption capacity of 70% IPA, and enhanced SNAP loading after 15 min. These properties enable significantly greater SNAP release within 30 min. Zone of inhibition demonstrated higher porosity leads to more significant inhibition of <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i>, <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, and <i>Candida albicans</i>. The disinfection of needleless connectors demonstrated a 2.91-, 7.04-, 2.02-, 3.21-, and 5.65-log reduction in <i>E. coli</i>, <i>P. aeruginosa</i>, <i>S. aureus</i>, <i>S. epidermidis</i>, and <i>C. albicans</i> viability after 30 min. These findings highlight the potential of this approach for efficient microbial decontamination in healthcare settings while offering adaptability for diverse biomedical applications.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":" ","pages":""},"PeriodicalIF":4.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combating Counterfeit Drugs via Machine Learning-Enabled Array Screening of Multilayer Evolutionary Combinatorial Libraries.","authors":"Huihai Li, Hao Chen, Weiwei Ni, Yutao Jin, Shen Wang, Sirong Liu, Qinxin Xia, Xu Gao, Shuang Du, Meng Zhang, Hui Huang, Fei Li, Jinsong Han, Yanliang Zhang","doi":"10.1021/acsami.5c13525","DOIUrl":"https://doi.org/10.1021/acsami.5c13525","url":null,"abstract":"<p><p>Counterfeit drugs are a global issue that has a serious impact on patient morbidity and mortality. Driven by nonspecific cross-reactivity, sensor arrays enable the concurrent discrimination of structurally related drug molecules. Nevertheless, rapidly generating sensor element libraries without a labor-intensive synthesis remains a major challenge. Herein, we present a machine learning-guided, three-layer screening strategy to identify the minimal optimal combination of sensing elements to combat counterfeit nonsteroidal anti-inflammatory drugs (NSAIDs), using a combinatorially designed library with 100 candidates. Following screening, a pruned 5-element array was successfully constructed, achieving 100% accuracy in distinguishing among nine NSAIDs and their analogs. Furthermore, the pruned arrays successfully achieved quantitative and multiplexed differentiation of two key NSAIDs. Notably, this strategy accurately discriminated five commercially available over-the-counter (OTC) NSAIDs from two counterfeit counterparts, achieving 100% accuracy within 5 min. These findings pave the way for constructing combinatorial sensing libraries for array-based screening and establish a foundation for a wide range of drug authenticity verification.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atomic Layer Deposition of Zinc-Oxide Layers for Photoassisted Lithium Metal Batteries.","authors":"Weizhai Bao, Hao Shen, Ronghao Wang, Chengfei Qian, Yaoyu Wang, Yangyang Zhang, He Liu, Cong Guo, Feng Yu, Bin Quan, Jingfa Li, Kaiwen Sun","doi":"10.1021/acsami.5c11206","DOIUrl":"https://doi.org/10.1021/acsami.5c11206","url":null,"abstract":"<p><p>The lithium metal anode offers a high theoretical capacity (3860 mAh g^-1) and a low electrochemical potential (-3.040 V vs SHE). These properties make it a promising candidate for use as an anode in next-generation lithium-ion batteries. However, the uneven deposition and stripping of lithium lead to dendrite growth and instability of the solid electrolyte interface. These problems seriously hinder the practical application of lithium metal batteries. Stable Li anodes enabled by a uniform lithiophilic nucleation layer and photoassisted current collectors are highly desirable. However, only a few studies have explored this approach. In this work, a thin ZnO layer was conformally deposited onto a 3D current collector via atomic layer deposition (ALD) to achieve uniform and stable lithium metal growth. The ZnO layer serves as a lithium nucleation layer and provides photoresponsiveness, thereby facilitating subsequent photoassisted deposition. This modification induced local carrier redistribution, reduced the overpotential by 25.5 mV, and significantly enhanced the lithium deposition kinetics. A high Coulombic efficiency of 96.56% was achieved at 3 mA cm^-2 after 300 cycles. These findings provide valuable insights into the development of next-generation photoassisted Li metal anodes, highlighting their potential for improved performance and stability.</p>","PeriodicalId":5,"journal":{"name":"ACS Applied Materials & Interfaces","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward Sustainable Scaled-Up Synthesis of Lignin-Derived Carbon Nanoparticles Using a Furnace Aerosol Reactor: Insights from a Life Cycle Assessment.","authors":"Sujit Modi, Yash Shah, Onochie Okonkwo, Leanne M Gilbertson, Pratim Biswas","doi":"10.1021/acs.est.5c06572","DOIUrl":"https://doi.org/10.1021/acs.est.5c06572","url":null,"abstract":"<p><p>A key aspect of circular economies is using sustainable pathways for processing advanced materials. While significant advances have been made in the discovery of novel materials that have innovative functionalities, rarely is attention provided to a holistic analysis to ensure that processes are sustainable. Rigorous analysis methodologies must be used to compare alternative processing methods. In this study, a comprehensive life cycle assessment (LCA) is conducted to evaluate a continuous and single-step aerosol synthesis approach in comparison to conventional batch pyrolysis methods for producing high-surface-area (porous) carbon materials. First, porous carbon nanoparticles (CNPs) are synthesized using a lab-scale aerosol reactor, and LCA is conducted to identify the key processing parameters contributing to their environmental impact. These results are then successfully used to guide the design of an optimized scaled-up aerosol reactor, achieving up to 75% reduction in global warming potential compared to conventional scaled-up batch pyrolysis techniques. Finally, the role of particle size and pyrolysis energy source in the environmental impact of CNP synthesis is systematically investigated. Overall, the simple (single-step, continuous, and rapid) operation and promising sustainability of the aerosol technique highlight its significant potential for the scalable synthesis of carbon nanomaterials from lignin.</p>","PeriodicalId":36,"journal":{"name":"环境科学与技术","volume":" ","pages":""},"PeriodicalIF":11.3,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}