JOURNAL OF HAZARDOUS MATERIALS
·
2024
·
IF 12.2
Xueping Jiang,Hao Li,Jia Kong,Yuqi li,Xiangdong Xin,Jielin Zhou,Ran Zhang,Kwang Sik Lee,Byung Rae Jin,Zhongzheng Gui
Microbial degradation of chloramphenicol (CAP) has become important for reducing the adverse impact of environmental pollution with antibiotics. Although several pathways for CAP degradation have been identified in various bacteria, multiple metabolic pathways and their respective intermediate metabolites within a single strain are rarely reported. Here, Raoultella ornithinolytica CT3 was first isolated from silkworm excrement using CAP as the sole carbon source, and 100 mg/L CAP was almost completely degraded within 48 h. The biodegradation type of CAP followed first-order kinetics. Twenty-two CAP biotransformation products were identified using high-performance liquid chromatography and ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry. The CAP biotransformation pathways were predicted mainly in the acetylation and auxiliary pathways of propionylation and butyrylation. The toxicity of CAP biotransformation products was evaluated using the ecological structure-activity relationship (ECOSAR) model and biological indicators. The results showed that the toxicity of the intermediate metabolites changed slightly, but the final metabolite was harmless to the environment. Genomic analysis predicted that genes encoding acetyltransferase, amido-linkage hydrolase, nitroreductase, haloacetate dehalogenase, and protocatechuate 3,4-dioxygenase were associated with CAP biodegradation. This study provides new insights into the microbial degradation pathway of CAP and constitutes an ecological safety assessment for CAP-contaminated environments.
研究领域:
环境微生物学
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生物降解
·
毒理学
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DOI
PubMed
高影响因子
CELL
·
2023
·
IF 64.5
Fangfei Qin,Boyuan Li,Hui Wang,Sihui Ma,Jiaofeng Li,Shanglin Liu,Linghao Kong,Huangtao Zheng,Rongfeng Zhu,Yu Han,Mingdong Yang,Kai Li,Xiong Ji,Peng R. Chen
A generalizable strategy with programmable site specificity for in situ profiling of histone modifications on unperturbed chromatin remains highly desirable but challenging. We herein developed a single-site-resolved multi-omics (SiTomics) strategy for systematic mapping of dynamic modifications and subsequent profiling of chromatinized proteome and genome defined by specific chromatin acylations in living cells. By leveraging the genetic code expansion strategy, our SiTomics toolkit revealed distinct crotonylation (e.g., H3K56cr) and β -hydroxybutyrylation (e.g., H3K56bhb) upon short chain fatty acids stimulation and established linkages for chromatin acylation mark-defined proteome, genome, and functions. This led to the identification of GLYR1 as a distinct interacting protein in modulating H3K56cr′s gene body localization as well as the discovery of an elevated super-enhancer repertoire underlying bhb-mediated chromatin modulations. SiTomics offers a platform technology for elucidating the “metabolites-modification-regulation” axis, which is widely applicable for multi-omics profiling and functional dissection of modifications beyond acylations and proteins beyond histones.
研究领域:
分子生物学
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表观遗传学
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基因组学
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蛋白质组学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Xi He,Xuezhe Liu,Jin Yang,Haibo Du,Ningwen Chai,Zhou Sha,Mengru Geng,Xiaojun Zhou,Chuanglong He
Natural polymeric hydrogel featuring multifunctional properties is more attractive as wound dressing. Herein, Tannic acid (TA)-reinforced methacrylated chitosan (CSMA)/methacrylated silk fibroin (SFMA) hydrogels were fabricated by two-step method of photopolymerization and TA solution incubating treatment. The TA in hydrogels not only served as second crosslinker improving the mechanical performance of up to a 5-fold increase (5 % TA treatment) than the pristine one, but also as functional molecule that endowed the hydrogels with enhanced adhesiveness and antioxidative properties. Besides, the introduction of TA into hydrogels further improved the antimicrobial activities against both Escherichia coli ( E. coli ) and Staphylococcus Aureus ( S. aureus ), as well as the cytocompatibility on fibroblasts. Moreover, it was demonstrated that the TA-treated CSMA/SFMA hydrogels could significantly promote wound healing in a full-thickness skin defect model. Collectively, these results showed that TA-reinforced CSMA/SFMA hydrogels could be a promising candidate as wound dressing.
研究领域:
生物材料学
·
医学
·
高分子化学
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DOI
PubMed
高影响因子
Cell Death & Disease
·
2023
·Vol. 14
·期 4
·1-10
·
IF 9
Xia Kangkai,Li Shujing,Yang Yuxi,Shi Xiaoxia,Zhao Binggong,Lv Linlin,Xin Zhiqiang,Kang Jie,Ren Ping,Wu Huijian
Breast cancer is the most commonly diagnosed cancer, and its global impact is increasing. Its onset and progression are influenced by multiple cues, one of which is the disruption of the internal circadian clock. Cryptochrome 2 (Cry2) genetic dysregulation may lead to the development of some diseases and even tumors. In addition, post-translational modifications can alter the Cry2 function. Here, we aimed to elucidate the post-translational regulations of Cry2 and its role in breast cancer pathogenesis. We identified p300-drived acetylation as a novel Cry2 post-translational modification, which histone deacetylase 6 (HDAC6) could reverse. Furthermore, we found that Cry2 inhibits breast cancer proliferation, but its acetylation impairs this effect. Finally, bioinformatics analysis revealed that genes repressed by Cry2 in breast cancer were mainly enriched in the NF-κB pathway, and acetylation reversed this repression. Collectively, these results indicate a novel Cry2 regulation mechanism and provide a rationale for its role in breast tumorigenesis.
研究领域:
肿瘤学
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分子生物学
·
癌症生物学
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产品关联
DOI
PubMed
高影响因子
GENOMICS PROTEOMICS & BIOINFORMATICS
·
2022
·
IF 6.409
Jiazhen Zheng,Yue Li,Ning Liu,Jihui Zhang,Shuangjiang Liu,Huarong Tan
Streptomycetes possess numerous gene clusters and the potential to produce large amounts of natural products. Histone deacetylase (HDAC) inhibitors play an important role in the regulation of histone modifications in fungi, but little is known about the roles of HDAC in prokaryotes. Here, we described the global effects of the HDAC inhibitor, sodium butyrate (SB), on marine-derived Streptomyces olivaceus FXJ 8.021, particularly on the activation of secondary metabolites biosynthesis. antiSMASH analysis revealed 33 secondary metabolite biosynthetic gene clusters (BGCs) in strain FXJ 8.021, among which the silent lobophorin BGC was activated by SB. Transcriptomic data showed that the expression of genes involved in lobophorin biosynthesis ( ge00097–ge00139 ) and CoA-ester formation ( e.g. , ge02824 ), as well as glycolysis/gluconeogenesis pathway ( e.g ., ge01661 ), was mainly up-regulated in the presence of SB. Intracellular CoA-ester analysis confirmed that SB triggered the biosynthesis of CoA-ester, increasing the precursor supply for lobophorin biosynthesis. Further acetylome analysis revealed that the acetylation levels on 218 acetylation sites of 190 proteins were up-regulated and those on 411 sites of 310 proteins were down-regulated. These acetylated proteins were particularly enriched in transcriptional and translational machinery components ( e.g ., elongation factor GE04399), and their correlations with the proteins involved in lobophorin biosynthesis were established by protein-protein interaction network analysis, suggesting that SB might function via a complex hierarchical regulation to activate expression of lobophorin BGC. These findings provide solid evidence that acetylated proteins triggered by SB could affect the expression of genes in the biosynthesis of primary and secondary metabolites in prokaryotes.
研究领域:
微生物学
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分子生物学
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生物化学
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基因组学
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DOI
PubMed
高影响因子
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
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2017
·
IF 2.24
Jie Sun,Liang Chen,Bo Lou,Yanbing Bai,Xinjun Yu,Man Zhao,Zhao Wang
Sucralose is a non-nutritive artificial sweetener used in a broad range of foods and beverages. In the present study, Bacillus amyloliquefaciens WZS01 was isolated, identified, and used as a catalyst both in regioselective acylation and deacetylation for sucralose preparation. Bacterial cells were immobilized on polyurethane foam and utilized to synthesize sucrose-6-acetate regioselectively. The yield of sucrose-6-acetate was >95% with 60 mM sucrose after 22 h of reaction. Free cells could hydrolyze 75 mM sucralose-6-acetate to produce sucralose with >99% yield after 24 h of reaction. B. amyloliquefaciens WZS01 could be considered a potential biocatalyst for sucralose preparation.
研究领域:
微生物学
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食品科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2018
·
IF 4.946
Yongsheng Chen,Jiangwei Liu,Sheng Geng,Yonglan Liu,Hanjun Ma,Jie Zheng,Benguo Liu,Guizhao Liang
Herein, we perform the regioselective acetylation of phloridzin catalyzed by immobilized Candida antarctica lipase B (CALB). We show that the enzyme amount and reaction time can significantly influence the composition of mono-, di- and tri-acetylated phloridzin in the product. The last acetylated derivative of phloridzin is isolated and identified as 4, 3″, 6″-3-O-acetyl-phloridzin by HPLC, UV, IR, MS and NMR. Molecular docking suggests that the first acetylation of phloridzin catalyzed by CALB occurs in 6″-OH, followed by 3″-OH, then 4-OH. During this process, hydrogen bond and hydrophobic forces play an important role in maintaining the binding interaction of CALB with phloridzin or its acetylated derivatives. Although, tri-acetylated phloridzin has moderate to minimal adverse-effects on LO-2, its anti-proliferative activity against human HepG2 cancer cells is superior to that of phloridzin, which attributes to its high capacity of inducing cell apoptosis, retarding cell cycle, lowering mitochondrial membrane potential and scavenging intracellular ROS.
研究领域:
生物化学
·
药物化学
·
肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Zhiqiang Lu,Xiaomeng Xu,Dongmei Li,Na Sun,Songyi Lin
Memory impairment is becoming a potential health issue with the delicacy of diet and social stress. Sea cucumber peptides (SCP) prevent memory impairment, as previously reported. In this study, further research was performed using hippocampal lysine-acetylome to explore molecular regulation mechanisms. C57BL/6 mice were treated with scopolamine via intraperitoneal injection to simulate memory impairment. To determine the influence of SCP on the total acetylated-protein level of the hippocampus, acetylated-proteomics was performed. SCP increased the acetylation level of histone (H3 and H4). Meanwhile, for non-histones, the differentially acetylated proteins were involved in multiple memory-related pathways, as shown by KEGG enrichment analysis. Additionally, long-term potentiation was confirmed by western blotting. Finally, a combined analysis of proteome and lysine acetylome revealed that SCP contributed to synaptic vesicle cycle regulation and dopamine metabolism. Consequently, our findings revealed that SCP was potentially neuroprotective by regulating post-transcriptional hippocampal protein acetylation.
研究领域:
神经科学
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蛋白质组学
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 17
·e70815
·
IF 4.2
Yang Tian,Wei Li,Qing Zhai,Ying Yu,Jiaxin Yuan,Yan Ma,Jingjing Yang,Mingyue Li,Wenwen Chang,Wenjing Li,Keke Huang,Chongran Sun,Chen Zeng,Yingdi Sun,Jiabao Gu,Huilin Zhang,Dameng Li,Yanan Yu,Lu Hu,Peng Zhang,Bo Ma,Junnian Zheng,Pan Li,Feng Guo,Yang Sun
Protein S‐palmitoylation, a dynamic and reversible post‐translational modification involving the attachment of palmitate to cysteine residues, is a key regulator of protein functionality and cellular signalling. Dysregulation of this modification has emerged as a critical driver of cancer progression. Among the 23 DHHC palmitoyl transferases responsible for catalysing S‐palmitoylation, aberrant expression of specific members is linked to tumorigenesis and development, underscoring their potential as promising therapeutic targets. However, the cancer‐specific roles and substrates of individual DHHC enzymes remain poorly characterised. In this study, we identified DHHC9 as a crucial regulator of adenocarcinoma progression, including colorectal and lung cancers. Functional studies demonstrated that DHHC9 knockdown profoundly inhibited cell migration in vitro and tumour metastasis in vivo. Proteomic and functional analyses revealed that STRN4, a core component of the STRIPAK complex, was palmitoylated by DHHC9 at cysteine 701. The STRN4 palmitoylation reduced YAP phosphorylation, promoted nuclear translocation of YAP and activated downstream Hippo pathway transcriptional targets—including CCN1, CCN2 and ANKRD1—thereby driving cancer cell migration. Notably, we discovered two small molecules, Treprostinil and 10‐HCPT, as potent DHHC9 inhibitors that effectively suppressed adenocarcinoma cell migration. Our findings define the DHHC9‐STRN4‐YAP axis as a novel mechanism linking palmitoylation to phosphatase regulation and Hippo pathway dysregulation, unveiling DHHC9 as a highly promising therapeutic target in cancer treatment.
研究领域:
癌症生物学
·
生物化学
·
分子生物学
·
药理学
·
细胞信号传导
·
蛋白质组学
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产品关联
DOI
PubMed
高影响因子
PLoS Pathogens
·
2024
·Vol. 20
·期 10
·e1012675
·
IF 5.5
Lijun Wang,Zhe Wang,Hua Zhang,Qian Jin,Shuaihua Fan,Yanni Liu,Xueting Huang,Jun Guo,Chao Cai,Jing-ren Zhang,Hui Wu
Klebsiella pneumoniae , an emerging multidrug-resistant pathogen, exhibits hypermucoviscosity (HMV) as a critical virulence trait mediated by its capsular polysaccharide (CPS). Recent discoveries have determined acetylation as a significant modification for CPS, although its impact on HMV and virulence was previously unknown. This study elucidates the roles of two enzymes: K lebsiella p neumoniae A cetylated C PS E sterase (KpACE), an esterase that removes acetyl groups from CPS, and WcsU, an acetyltransferase that adds acetyl groups to CPS. KpACE is highly upregulated in an ompR -deficient mutant lacking HMV, and its overexpression consistently reduces HMV and diminishes virulence in a mouse model of pneumonia. The esterase domain-containing KpACE effectively deacetylates model sugar substrates and CPS-K2. Site-directed mutagenesis of the conserved catalytic histidine residue at position 370 significantly reduces its enzymatic activity. This reduction correlates with decreased HMV, affecting key virulence traits including biofilm formation and serum resistance. Similarly, a deficiency in the wcsU gene abolishes CPS acetylation, and reduces HMV and virulence. These results highlight the importance of the delicate balance between CPS acetylation by WcsU and deacetylation by KpACE in regulating the pathogenicity of K . pneumoniae . Understanding this balance provides new insights into the modulation of virulence traits and potential therapeutic targets for combating K . pneumoniae infections.
Klebsiella pneumoniae is an antibiotic-resistant pathogen known for its virulence factor, hypermucoviscosity (HMV), which relies on the production of capsular polysaccharides (CPS). This study highlights the roles of two key enzymes: KpACE, an esterase that removes acetyl groups from CPS, and WcsU, an acetyltransferase that adds acetyl groups to CPS. Overexpression of KpACE reduces HMV and decreases virulence in a mouse pneumonia model by deacetylating CPS. Conversely, a deficiency in the wcsU gene, which is responsible for acetylating CPS, also results in decreased HMV and virulence. The balance between CPS acetylation by WcsU and deacetylation by KpACE is crucial in regulating K . pneumoniae pathogenicity. This balance affects various virulence factors, including biofilm formation and serum resistance, highlighting the importance of CPS acetylation dynamics in the pathogen’s fitness and virulence. Understanding these mechanisms offers insights into potential therapeutic targets to mitigate the virulence and antibiotic resistance of K . pneumoniae .
研究领域:
微生物学
·
传染病学
·
分子生物学
·
致病机制
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产品关联
DOI
PubMed
高影响因子
CELLULAR SIGNALLING
·
2024
·
IF 4.4
Yun Zhou,Song Yue,Lihua Li,Jiahua Zhang,Lei Chen,Jun Chen
Abnormal inflammation of vascular endothelial cells occurs frequently in diabetic retinopathy (DR). Sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B) is a lipid raft enzyme and plays an anti-inflammatory role in various diseases but its function in DR-related vascular endothelial dysfunction remains unknown. We first found that SMPDL3B expression was upregulated from week 10 to 18 in the retinal tissues of db/db mice. Particularly, the high expression of SMPDL3B was mainly observed in retinal vascular endothelium of DR mice. To interfere retinal SMPDL3B expression, adeno-associated viruses 2 (AAV-2) containing SMPDL3B specific shRNA (1233–1253 bp) were injected into the vitreous cavity of db/db mice. SMPDL3B silencing exacerbated the spontaneous DR by further activating the NF-κB/NLRP3 pro-inflammatory pathway. In vitro , human retinal microvascular endothelial cells (HRVECs) were infected with SMPDL3B-shRNA lentiviruses and then stimulated with 30 mM glucose (HG) for 24 h. SMPDL3B-silenced HRVECs secreted more interleukin-1β and had enhanced nuclear p65 translocation. Notably, HG treatment induced the palmitoylation of SMPDL3B. Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a palmitoyltransferase that catalyzes the palmitoylation of its substrates, HG exposure increased the interaction between ZDHHC5 and SMPDL3B in HRVECs. 2-BP, a palmitoylation inhibitor, accelerated the protein degradation of SMPDL3B, whereas palmostatin B, a depalmitoylation inhibitor, decreased its turnover rate in HRVECs. Collectively, the present study suggests a compensatory increase of SMPDL3B in HG-treated HRVECs and the retinal tissues of DR mice, indicating that SMPDL3B may be a potential target for DR treatment.
研究领域:
糖尿病
·
视网膜疾病
·
分子生物学
·
细胞生物学
·
炎症
·
基因治疗
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF INVESTIGATIVE DERMATOLOGY
·
2020
·
IF 7.143
Xiaoxuan Yu,Hui Li,Mengyuan Zhu,Po Hu,Xiao Liu,Yingjie Qing,Xiangyuan Wang,Hongzheng Wang,Zhanyu Wang,Jingyan Xu,Renxiang Tan,Qinglong Guo,Hui Hui
Cutaneous T-cell lymphomas (CTCLs) represent a rare form of non-Hodgkin lymphomas characterized by an accumulation of malignant CD4 + T cells in the skin. TP53 genetic alteration is one of the most prevalent genetic abnormalities in CTCLs. Therefore, it is a promising target for innovative therapeutic approaches. We found that p53 could physically interact with histone deacetylase (HDAC) 1 and HDAC8, and was subsequently deacetylated to lose its function in CTCL cells, and the p53 downstream apoptosis-associated genes were repressed. Thus, the anti-CTCL activity displayed by HDAC inhibitors depends on p53 status. However, recent studies have reported that HDAC inhibitors could induce a wide variety of drug-resistant characteristics in cancer cells by regulating ATP-binding cassette transporters. Moreover, we discovered that Baicalein, a natural product, exhibited an inhibitory effect on HDAC1 and HDAC8. Though the inhibition of HDAC1 was mild, Baicalein could induce the degradation of HDAC1 through the ubiquitin proteasome pathway, thereby markedly upregulating the acetylation of histone H3 without promoting ATP-binding cassette transporter gene expression. In terms of the mechanism, Baicalein showed better growth inhibition than traditional HDAC inhibitors in CTCLs. This study indicates a special mechanism of HDAC1 and HDAC8 and p53 in T-cell lymphoma cells and identifies a potential and safe natural HDAC inhibitor for the treatment of CTCLs.
研究领域:
肿瘤学
·
分子生物学
·
药理学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）