ChemBioChem最新文献_第2页

Synthesis and Fluorescence Profiling of Naphthylamine Analogs 萘胺类似物的合成及荧光谱分析

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-10-09 DOI: 10.1002/cbic.70569

Cole M. Friederichs, Jackson W. Berryman, Quentin M. R. Gibaut, Inga V. Leus, Chloe F. Cox, Helen I. Zgurskaya, Adam S. Duerfeldt

{"title":"Synthesis and Fluorescence Profiling of Naphthylamine Analogs","authors":"Cole M. Friederichs, Jackson W. Berryman, Quentin M. R. Gibaut, Inga V. Leus, Chloe F. Cox, Helen I. Zgurskaya, Adam S. Duerfeldt","doi":"10.1002/cbic.70569","DOIUrl":"https://doi.org/10.1002/cbic.70569","url":null,"abstract":"N-phenyl-1-naphthylamine (NPN) has been widely used to probe the integrity of the outer membrane of gram-negative bacteria. NPN fluoresces in the hydrophobic environment of lipid bilayers, whereas its fluorescence is quenched in the aqueous extracellular milieu. Because NPN does not intrinsically accumulate in intact gram-negative bacteria, it has been broadly applied as a reporter of outer membrane permeabilization. Despite its widespread utility, systematic derivatization of this probe has remained largely unexplored. Here, we investigated the structure–fluorescence relationships of NPN through the synthesis of a diverse library featuring varied linkages to the fluorogenic naphthylamine core. Subsequent library expansion was informed by density functional theory and time-dependent density functional theory studies, which suggested possible origins of fluorescence quenching in aqueous environments. The final resulting library comprised 95 compounds, of which 49 exhibited a fluorogenic profile similar to that of NPN. A selected subset of analogs was then evaluated in a fluorescence-based accumulation assay using varied efflux and permeation strains of Escherichia coli, revealing that installed structural motifs influenced bacterial permeation. Collectively, these probes provide a foundation for further studies examining how small structural changes affect accumulation in gram-negative bacteria.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149146107","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

Chemical Biology-Based Drug Discovery Workflow Highlights Target Identification as a Key Step in Developing a Novel, Potent, and Selective GLUT1 Inhibitor 基于化学生物学的药物发现工作流程强调目标识别是开发新型、有效和选择性GLUT1抑制剂的关键步骤。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-10-06 DOI: 10.1002/cbic.70556

Hiroshi Kamiyama, Yuji Onizawa, Kenji Kubara, Yasunobu Matsumoto, Koji Sagane, Masaharu Gotoda, Takayuki Miyazaki, Yuta Suzuki, Yoshihiko Kotake, Yasutaka Takase, Yosuke Kaburagi

{"title":"Chemical Biology-Based Drug Discovery Workflow Highlights Target Identification as a Key Step in Developing a Novel, Potent, and Selective GLUT1 Inhibitor","authors":"Hiroshi Kamiyama, Yuji Onizawa, Kenji Kubara, Yasunobu Matsumoto, Koji Sagane, Masaharu Gotoda, Takayuki Miyazaki, Yuta Suzuki, Yoshihiko Kotake, Yasutaka Takase, Yosuke Kaburagi","doi":"10.1002/cbic.70556","DOIUrl":"10.1002/cbic.70556","url":null,"abstract":"Discovery of bioactive compounds with novel chemical scaffolds remains a cornerstone of drug discovery. We designed a spiro scaffold composed of a cyclic imide and a diazepane to construct a focused compound library with minimal diversity. Screening for HCT-116 cell growth inhibition, supported by growth curve analysis and structural optimization, identified compounds 1a and 2a as a chemical probe and a lead candidate, respectively. Compound 2a displayed a distinctive gene expression profile and reduced the viability of U251 cells within the JFCR39 cancer cell panel. A fluorescent probe derived from 1a, localized to the cell membrane, provided crucial information for cell lysate preparation and the affinity-based identification of facilitative glucose transporter type 1 (GLUT1) as a candidate target protein. Resistance to 2a was linked to a mutation at position N411 in GLUT1, and cells expressing the GLUT1N411K mutant showed marked attenuation of both antiproliferative and glucose-uptake inhibitory activities. In this study, we discuss the impact of an integrated approach from hit compound discovery to target identification, as well as 2a, a notable GLUT1 inhibitor that exhibits robust activity attributable solely to GLUT1 inhibition.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101450","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

Chemoenzymatic Synthesis of (4R,7R)-Zingiberene Enables Construction of nor-Sesquiterpene Semiochemical Analogs 化学酶法合成(4R,7R)-姜绿烯，构建非倍半萜半化学类似物。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-10-06 DOI: 10.1002/cbic.70534

Luke A. Johnson, Jennifer C. R. Benton, Chris Jones, Oktawia Kuzba, David J. Miller, John A. Pickett, Rudolf K. Allemann

{"title":"Chemoenzymatic Synthesis of (4R,7R)-Zingiberene Enables Construction of nor-Sesquiterpene Semiochemical Analogs","authors":"Luke A. Johnson, Jennifer C. R. Benton, Chris Jones, Oktawia Kuzba, David J. Miller, John A. Pickett, Rudolf K. Allemann","doi":"10.1002/cbic.70534","DOIUrl":"10.1002/cbic.70534","url":null,"abstract":"The wild tomato sesquiterpene (4R,7R)-zingiberene (6a) acts as a potent repellent of the economically important agricultural pest, the silverleaf whitefly (Bemisia tabaci). While its biosynthesis is catalyzed by 7-epi-zingiberene synthase from the noncanonical terpene precursor (2Z,6Z)-farnesyl pyrophosphate (5a), the precise enzymatic mechanism has remained undetermined. Using deuterated substrates generated chemoenzymatically, the 1,6-cyclization mechanism was established to proceed via a 1,3-hydride shift from the C1 position of the initial bisabolyl carbocationic intermediate. Product diversity was expanded by identifying two single residue switches within the G1/2 helix that govern enzyme fidelity, thereby redirecting product distributions to alternative C6-cyclized zingiberenols as well as γ- and β-curcumene. Applying this chemoenzymatic synthesis with alternative allyl alcohols plus isoprenol enabled the production and structural diversification of two novel nor-sesquiterpene analogs (C14/C16), 13-nor-(4R,7R)-zingiberene (23) and 12-ethyl-13-nor-(4R,7R)-zingiberene (24). Notably, these syntheses were only possible because the tomato (2Z,6Z)-farnesyl pyrophosphate synthase overcomes conventional prenyltransferase substrate selectivity to catalyze chain extension via atypical secondary allyl carbocation intermediates. The catalytic promiscuity provides opportunities to engineer terpene products with diverse methyl-branching patterns, providing the platform to investigate the molecular basis of terpene semiochemical activity needed for the development of broad-spectrum repellents to sustainably manage insect pests in agriculture.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101498","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

Recent Progress in Understanding the Mechanism of Formate Dehydrogenases 甲酸脱氢酶作用机理的研究进展。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-10-06 DOI: 10.1002/cbic.70555

Russ Hille, Dimitri Niks

引用次数: 0

The Strategies of Integrating 4-Nitro-3-trifluoromethylaniline With Photosensitizers for Combined NO Gas and Photodynamic Therapy 4-硝基-3-三氟甲基苯胺与光敏剂集成用于NO气体光动力联合治疗的策略

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-30 DOI: 10.1002/cbic.70538

Tong Sun, Shaoqi Xie, Mengqi Liu, Yuqing Liu, Jiachen Xia, Bing Lu

{"title":"The Strategies of Integrating 4-Nitro-3-trifluoromethylaniline With Photosensitizers for Combined NO Gas and Photodynamic Therapy","authors":"Tong Sun, Shaoqi Xie, Mengqi Liu, Yuqing Liu, Jiachen Xia, Bing Lu","doi":"10.1002/cbic.70538","DOIUrl":"10.1002/cbic.70538","url":null,"abstract":"Nowadays, an increasing number of emerging therapeutic modalities are flourishing due to the high recurrence and intractability of cancer. Among them, NO gas therapy (NO GT) relies on NO donors that release NO radicals upon external or internal stimulation. Photodynamic therapy (PDT) is realized by the specific photosensitizers and light source. However, the clinical translation of NO is limited by its gaseous nature and the need for precise control over dosage and spatiotemporal distribution. Meanwhile, the efficacy of PDT is often compromised by tumor hypoxia. Consequently, the synergistic integration of PDT and NO GT has emerged as a cutting-edge paradigm in cancer treatment. Among the various NO donors, 4-nitro-3-trifuoromethylaniline (NTA) and its derivatives, as a prominent class of NO photodonors, have garnered sustained attention, which displayed various advantages such as high and controllable NO release ability and outstanding structural modification. In this review, we highlight the design of such bimodal therapeutic systems based on two methods of the combination of NTA and photosensitizers, namely, nanoassembly and molecular hybridization. By elucidating the design principles and synergistic antitumor effects of these two strategies, we summarize future development directions and remaining bottlenecks to provide rational guidelines for subsequent molecular design and biomedical research.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101466","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

Mechanistic Analysis of Albumin–Ruthenium Conjugates Reveals Redox-Sensitive Catalytic Persistence for Extracellular Prodrug Uncaging 白蛋白-钌偶联物的机制分析揭示了细胞外前药溶出的氧化还原敏感催化持久性。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-30 DOI: 10.1002/cbic.70560

Prabhat Neupane, Parastoo Pourali, Lily F. Garrett, Huong Giang Pham, Alexander R. French, Elliott B. Hulley, Timothy D. Eubank, Takashi L. Suyama

{"title":"Mechanistic Analysis of Albumin–Ruthenium Conjugates Reveals Redox-Sensitive Catalytic Persistence for Extracellular Prodrug Uncaging","authors":"Prabhat Neupane, Parastoo Pourali, Lily F. Garrett, Huong Giang Pham, Alexander R. French, Elliott B. Hulley, Timothy D. Eubank, Takashi L. Suyama","doi":"10.1002/cbic.70560","DOIUrl":"10.1002/cbic.70560","url":null,"abstract":"Selective use of cytotoxic agents remains limited by systemic exposure and heterogeneous delivery in solid tumors. Extracellular catalytic prodrug activation offers a complementary strategy in which a pericellular catalyst activates a diffusible caged payload without requiring carrier internalization. This approach requires catalysts that retain activity under extracellular redox conditions and concentrate near cells through local binding environments. Here, we use albumin–ruthenium conjugates (ARCs) to define how redox environment and secreted protein acidic and rich in cysteine (SPARC), an albumin-binding extracellular matrix glycoprotein, shape extracellular catalyst persistence and local albumin association. ARCs uncaged alloc-protected fluorescent and doxorubicin substrates at low micromolar concentrations with limited intrinsic cytotoxicity. Catalytic activity was attenuated under ambient oxygen but preserved under oxygen-limited or antioxidant conditions, consistent with oxygen/redox-associated catalyst deactivation. ARC retained uncaging activity after SPARC capture and washing, indicating that SPARC association does not block catalyst accessibility. In cell-based assays, SPARC-expressing 4T1 and BT-549 cells showed rapid albumin association, whereas low-SPARC MCF10A cells exhibited weaker early association enhanced by exogenous SPARC. Fluorescence imaging, trypan blue quenching, and washed-cell uncaging assays support a predominantly extracellular/pericellular mechanism that does not require carrier internalization. Together, these results identify redox-sensitive catalytic persistence and SPARC-enhanced albumin capture as mechanistic parameters governing extracellular albumin-based artificial metalloenzyme function.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101474","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

A Gas Chromatography-Based Workflow Leads to the Detection of Hydrogenase Activity in Native Bacteria 基于气相色谱的工作流程可用于检测天然细菌中的氢化酶活性。

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-30 DOI: 10.1002/cbic.70545

Marius Stoeckle, Kersten S. Rabe, Christof M. Niemeyer

{"title":"A Gas Chromatography-Based Workflow Leads to the Detection of Hydrogenase Activity in Native Bacteria","authors":"Marius Stoeckle, Kersten S. Rabe, Christof M. Niemeyer","doi":"10.1002/cbic.70545","DOIUrl":"10.1002/cbic.70545","url":null,"abstract":"Functional assessment of hydrogenase activity in native bacterial systems is often complicated by the requirements associated with enzyme purification, heterologous expression, and cofactor maturation. Here, we present a standardized gas chromatography-based workflow for the direct assessment of hydrogenase activity in crude membrane and lysate fractions without enzyme purification or genetic manipulation. The workflow was applied to a defined panel of phylogenetically distinct bacterial strains. Hydrogen oxidation activity was detected in Shewanella acanthi and Insolitispirillum peregrinum. Burkholderia plantarii exhibited low but reproducible hydrogen oxidation activity despite the absence of a clear hydrogenase candidate in the annotation-based search applied here. This observation prompted further screening of Paraburkholderia mimosarum, P. xenovorans, P. kururiensis, P. phenoliruptrix, and P. phymatum, revealing hydrogen oxidation activity across these related strains. Among the initially investigated nonmodel organisms, I. peregrinum exhibited the highest hydrogen oxidation activity and showed prolonged activity, partial oxygen tolerance, and substantial activity at elevated temperatures. Hydrogen production was consistently lower than hydrogen oxidation under the applied assay conditions. Overall, the workflow provides a practical approach for comparative screening of hydrogen-converting activity in native bacterial fractions and can support the selection of candidate systems for further biochemical characterization.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101489","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

Decoupling Photophysical Brightness and Cellular Imaging Efficiency in 4-ANI-Based Fluorophores: The Critical Role of Sterically Hindered N-Substituents 4- ani基荧光团的解耦光物理亮度和细胞成像效率：位阻n取代基的关键作用

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-29 DOI: 10.1002/cbic.70553

Laurane Michel, Sophia Godel-Pastre, Narjis Ouazzani, Mélina Fabe, Siham El Mounquad, Mickaël Bourge, Stéphanie Deville-Foillard, Arnaud Chevalier

{"title":"Decoupling Photophysical Brightness and Cellular Imaging Efficiency in 4-ANI-Based Fluorophores: The Critical Role of Sterically Hindered N-Substituents","authors":"Laurane Michel, Sophia Godel-Pastre, Narjis Ouazzani, Mélina Fabe, Siham El Mounquad, Mickaël Bourge, Stéphanie Deville-Foillard, Arnaud Chevalier","doi":"10.1002/cbic.70553","DOIUrl":"https://doi.org/10.1002/cbic.70553","url":null,"abstract":"In this article, we report the screening of a library of twenty-one 4-ANI-based fluorophores, leading to the identification of a novel cycloheptylamine-containing derivative with outstanding performance for cellular imaging. This compound exhibits fluorescence intensities more than tenfold higher than those of most analogs, enabling its use at submicromolar concentrations with minimal perturbation of cellular function. Beyond this lead discovery, our results highlight a critical disconnect between photophysical properties in aqueous media and imaging efficiency in biological systems. By combining multiple analytical techniques, including photophysics, fluorescence microscopy, and flow cytometry as well as computational DFT calculations, we demonstrate that sterically hindered N-substituents play a critical role by combining efficient cellular uptake and good solubility, two essential features that govern probe performance for cell imaging. These findings challenge the conventional reliance on intrinsic brightness as a design criterion and emphasize the necessity of integrating biological context into the evaluation and development of fluorescent imaging agents.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072521","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

Nickel-Substituted Rubredoxin Undergoes Demetallation Upon Reaction With Nitric Oxide and Nitroxyl 镍取代红霉素与一氧化氮和硝基反应脱金属

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-29 DOI: 10.1002/cbic.70548

Eduardo H. S. Sousa, Thiago Maciel Bastos, Ana C. S. Gondim, Wellinson G. Guimarães, Marcelo H. M. da Silva, Marta S. P. Carepo, Sofia R. Pauleta, Isabel Moura, José J. G. Moura

{"title":"Nickel-Substituted Rubredoxin Undergoes Demetallation Upon Reaction With Nitric Oxide and Nitroxyl","authors":"Eduardo H. S. Sousa, Thiago Maciel Bastos, Ana C. S. Gondim, Wellinson G. Guimarães, Marcelo H. M. da Silva, Marta S. P. Carepo, Sofia R. Pauleta, Isabel Moura, José J. G. Moura","doi":"10.1002/cbic.70548","DOIUrl":"https://doi.org/10.1002/cbic.70548","url":null,"abstract":"Nitric oxide (NO) and nitroxyl (HNO) are closely related reactive nitrogen species with distinct biological functions, yet differentiating their chemistry remains challenging because of their high reactivity and overlapping reaction pathways. Developing simple protein-based platforms to study their reactivity is therefore of considerable interest. Rubredoxins are small, stable iron–thiolate proteins widely used as model systems for investigating metal–thiolate coordination and electron transfer. Here, we investigated the reactivity of native iron-rubredoxin (Fe-Rd) and its nickel-substituted analog (Ni-Rd) toward NO and HNO to determine whether cysteine ligand modification could disrupt metal–thiolate coordination and induce demetallation. Electronic absorption and fluorescence spectroscopy showed that Fe-Rd is highly resistant to both species, whereas Ni-Rd exhibited pronounced spectral changes consistent with metal release, including loss of the Ni─S ligand-to-metal charge-transfer band and increased intrinsic fluorescence. Inductively coupled plasma atomic emission spectroscopy confirmed partial nickel release following treatment with both NO and HNO donors. Despite demetallation, circular dichroism, thermal denaturation, and size-exclusion chromatography demonstrated that Ni-Rd largely retains its secondary structure, thermal stability, and monomeric state. These findings establish Ni-Rd as a robust minimal metalloprotein platform for probing reactive nitrogen species-induced thiolate chemistry.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70548","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072517","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

Functional Heterogeneity of the Autism Spectrum Disorder-Associated Gut Microbial Ecosystem Revealed by Fecal Lipopolysaccharides and Bacterial Proteomic Profiling 粪便脂多糖和细菌蛋白质组学分析揭示自闭症谱系障碍相关肠道微生物生态系统的功能异质性

IF 2.8 4区生物学

ChemBioChem Pub Date : 2026-09-29 DOI: 10.1002/cbic.70557

Stefania De Chiara, Angela Di Somma, Valentina Mazziotti, Serena Coppola, Franca Oglio, Lidia Tammaro, Maria Pia Riccio, Carmela Bravaccio, Antonio Molinaro, Roberto Berni Canani, Flaviana Di Lorenzo

{"title":"Functional Heterogeneity of the Autism Spectrum Disorder-Associated Gut Microbial Ecosystem Revealed by Fecal Lipopolysaccharides and Bacterial Proteomic Profiling","authors":"Stefania De Chiara, Angela Di Somma, Valentina Mazziotti, Serena Coppola, Franca Oglio, Lidia Tammaro, Maria Pia Riccio, Carmela Bravaccio, Antonio Molinaro, Roberto Berni Canani, Flaviana Di Lorenzo","doi":"10.1002/cbic.70557","DOIUrl":"https://doi.org/10.1002/cbic.70557","url":null,"abstract":"The etiology of pediatric autism spectrum disorder (ASD) has been increasingly linked to alterations in the gut-brain axis, highlighting the intricate bidirectional communication between gut microbiota and central nervous system. The molecular mechanisms of this communication are poorly understood. Here we investigated whether ASD-associated gut microbiota could exhibit altered inflammatory molecular outputs by integrating chemistry-driven profiling of fecal lipopolysaccharides (LPS), functional bacterial proteomics, and neuroimmune cellular assays. Structural analyses revealed that LPS from non-autistic healthy donors (NASD) displayed highly conserved carbohydrate and lipid A signatures dominated by hypo-acylated mono-phosphorylated species typically associated with immunomodulatory Bacteroides-derived LPS. In contrast, LPS from ASD children exhibited increased structural heterogeneity. These molecular alterations were functionally reflected in human HMC3 microglial cells, where ASD-derived fecal LPS induced stronger IL-6 and IL-8 release compared with NASD-derived LPS, indicating enhanced neuroinflammatory potential. Functional proteomic profiling disclosed broadly comparable microbial compositions but marked metabolic divergence. These findings suggest that gut microbiota in ASD children are associated with a functionally heterogeneous microbial ecosystem characterized by altered immunostimulatory molecular outputs despite the absence of massive taxonomic shifts, with potential relevance for neuroimmune dysregulation.","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":"27 19","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cbic.70557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072523","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