PLoS Genetics
·
2025
·Vol. 21
·期 8
·e1011815
·
IF 3.7
Qinqin Zhao,Liwei Gao,Nuo Xu,Xiuting Zhang,Yuqi Qin,Yinbo Qu,Guodong Liu
l -Fucose is a universal capping component of biomolecules found throughout all domains of life. Although fungi are renowned for their role in biomass recycling, the mechanisms by which they process l -fucose remain largely unknown. In this study, we elucidate a l -fucose-responsive system in Trichoderma reesei , a model fungus for plant cell wall degradation. Central to this system is the transcription factor FUR1, which is indispensable for growth on l -fucose. FUR1 orchestrates the expression of l -fucose catabolic enzymes, including an l -fucose dehydrogenase that exhibits distant homology to counterparts in bacteria and mammals. Through RNA sequencing and biochemical assays, we demonstrate that FUR1 also governs the enzymatic liberation of l -fucose by upregulating extracellular α- l -fucosidases. Intriguingly, FUR1 mediates l -fucose-triggered expression of a broad spectrum of enzymes that target diverse glycosidic bonds (e.g., β-glucuronidic, α-galactosidic, and β-xylosidic linkages) within complex carbohydrates. Expression of a constitutively active FUR1 mutant unlocked the production of otherwise silent glycosidases, substantially boosting the hydrolytic capacity of the fungal secretome on orange peel. These findings offer the first molecular insight into l -fucose sensing and metabolism in fungi, and advance our understanding of the fungal regulatory network for coordinated expression of biomass-degrading enzymes.
l -Fucose, is a widely present constituent of polysaccharides, glycoproteins, and glycolipids in plants, animals and bacteria. l -Fucose frequently presents itself as a terminal monosaccharide, and plays critical roles in cell communication, immunity and host-microbe interactions. While fungi are well-known for breaking down various biomass molecules (e.g., lignocellulose) in nature, their metabolic and regulatory machineries for l -fucose utilization are enigmatic. Here, we examine the transcriptional response of Trichoderma reesei to l -fucose. We discovered that an orphan transcription factor activates the expression of l -fucose catabolic enzymes as well as extracellular α- l -fucosidases. Additionally, we found that this transcription factor also mediates the cross-induction by l -fucose of a wide range of enzymes that break down different types of glycosidic bonds. These findings provide the first understanding of how a fungus senses and metabolize l -fucose, and shed light on the complex regulatory systems that allow fungi to efficiently degrade biomass. This knowledge could help improve industrial fungal strains for the production of more efficient biomass-degrading enzymes.
研究领域:
真菌学
·
分子生物学
·
生物化学
·
生物技术
·
基因组学
·
微生物生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Chemistry Frontiers
·
2016
·Vol. 1
·期 4
·660-667
·
IF 0
Xianfeng Hou,Jin Peng,Fang Zeng,Changmin Yu,Shuizhu Wu
Alpha-L-fucosidase (AFU) plays vital roles in some physiological processes that closely relate to several diseases. Herein, a ratiometric fluorescent probe for the alpha-L-fucosidase (AFU) assay based on a single fluorophore has been developed by functionalizing a new fluorophore platform (6-bromo-anthracenecarboximide) with an α-L-fucose group. AFU cleaves the α-L-fucose group from the probe molecule and remarkably alters its photophysical properties, thus realizing ratiometric detection of AFU. Due to the specificity and high efficiency of the enzymatic reaction, this probe can sensitively and selectively detect AFU in aqueous media and biological milieus with a detection limit of 0.0033 U mL−1. Moreover, the probe can be employed to monitor and spatially map endogenous AFU levels in a hepatocellular carcinoma (HCC) model of zebrafish. Hence, the probe holds significant promise for conducting pathological research on AFU-involved diseases.
研究领域:
生物化学
·
医学诊断
·
分子生物学
✓ 已验证
DOI
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Chen Xu,Xiang Shi,Huifang Sun,Lijuan Yu,Liang Zhang,Di Lan,Xiaolu Wu,Mengran Chen,Nanqi Cheng,Ying Pan,Jiayi He,Ronghua Yin,Lutan Zhou,Na Gao,Jinhua Zhao
Fucosylated glycosaminoglycan (FG) from Holothuroidea exhibits notable structural diversity and multiple biological activities. This study investigated the HfFG isolated from the sea cucumber Holothuria floridana , focusing on its chemical structure and biological activities. Structural analysis of eleven oligosaccharides (a-k) and a depolymerized product (dHfFG-II) using NMR identified the HfFG backbone as chondroitin sulfate E (CS-E), with various branches, including L-Fuc 2S4S , L-Fuc 3S4S , L-Fuc 4S , and the unique disaccharide D-GalNAc 4S -α1,2-L-Fuc 3S4S , attached at C-3 of GlcA. A high L-Fuc 2S4S (40 %) and disaccharide branch (35 %) content allowed their contiguous distribution within the CS-E chain, as evidenced by the predominant hexasaccharides (i, j) in size-homogeneous Fr4 and the novel nonasaccharide k in Fr5. Notably, previously unreported branches and sequences in HfFG were confirmed, offering new understanding of the natural HfFG structure. HfFG showed potent inhibitory activities on the intrinsic tenase complex (iXase), heparanase, and P-selectin binding to PSGL-1. Depolymerization selectively modulated these activities, preserving anti-iXase potency while attenuating heparanase and P-selectin inhibition. These activities were dependent on oligosaccharide chain length and sequence. Comparing the activities of FG and its oligosaccharides highlights their potential for the rational design of targeted inhibitors of heparanase or P-selectin binding to PSGL-1, with significant implications for therapeutic applications.
研究领域:
海洋生物学
·
生物化学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2019
·
IF 6.393
Xin Cheng,Yan Huang,Diying Li,Chao Yuan,Zi-Long Li,Linhao Sun,Hong Jiang,Jimei Ma
α- l -Fucosidase (AFu) is an important biomarker for early diagnosis of hepatocellular carcinoma and fucosidosis. In this study, a novel, sensitive and selective polymer dots (PDs) fluorescent sensing strategy based on inner filter effect was firstly developed for AFu activity determination. The PDs with a high quantum yield of 53.6% were synthesized by a mild one-pot method. The detection mechanism of this strategy was based on inner filter effect between PDs and p-nitrophenol (PNP) which was the hydrolyzate of 4-nitrophenyl-α- l -fucopyranoside (PNPF) catalyzed by AFu. The absorption of PNP overlapped the fluorescence excitation spectrum of the PDs, which resulted in a fluorescence quenching or weakening of PDs. The sensing system showed a good linear relationship within 0.01-0.9 U L −1 and provided a low AFu detection limit of 0.001 U L −1 (S/N = 3). This PDs sensor were successfully applied for the determination of AFu in human serum samples.
研究领域:
生物化学
·
医学诊断
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
GLYCOBIOLOGY
·
2016
·Vol. 26
·期 8
·871-879
·
IF 3.283
Liu Si,Kulinich Anna,Cai Zhi P,Ma Hong Y,Du Ya M,Lv Yong M,Liu Li,Voglmeir Josef
Three novel bacterial α-l-fucosidases, which cleave terminal fucosyl residues from glycoconjugates are reported in this work. Originating from the recently discovered bacterium Emticicia oligotrophica, recombinant fucosidase isoforms designated as Eo0918, Eo3066 and Eo3812 were shown to have the highest activity between pH 6.0 and 7.0 and temperature optima between 30 and 45°C. All enzymes catalyzed the hydrolysis of the model substrate pNP-α-l-fucose and revealed significantly different regiospecificities towards fucose-containing oligosaccharides: Eo0918 liberated exclusively α1,6-linked fucose and Eo3812 released only α1,3-fucosyl residues, whereas Eo3066 showed broader substrate promiscuity. The enzymatic activity of Eo0918 and Eo3812 increased upon the addition of Ca2+, Mn2+ and Zn2+ ions, whereas the activity of Eo3066 was significantly decreased in the presence of these metal ions. In addition, Eo0918 also catalyzed the transfer of fucose from pNP-α-l-fucose to the 7-hydroxyl group of 4-methylumbelliferone with up to 15% transglycosylation yield. Facile recombinant expression in E. coli, distinct substrate specificities and the transglycosylation ability of Eo0918 presented herein make these newly discovered fucosidases valuable candidates for bioanalytical and biotechnological applications.
研究领域:
微生物学
·
生物化学
·
生物技术
✓ 已验证
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2024
·
IF 4.5
Muhammad Waheed Iqbal,Xinrui Tang,Tahreem Riaz,Shahid Mahmood,Yufei Zhang,Mei Zhao,Junhua Yun,Jia Li,Xianghui Qi
6-Deoxy- l -sorbose (6-DLS) is an imperative rare sugar employed in food, agriculture, pharmaceutical and cosmetic industeries. However, it is a synthetic and very expensive rare sugars, previously synthesized by chemo-enzymatic methods through a long chain of chemical processes. Recently, enzymatic synthesis of rare sugars has attracted a lot of attention due to its advantages over synthetic methods. In this work, a promising approach for the synthesis of 6-DLS from an inexpensive sugar l -fucose was identified. The genes for l -fucose isomerase from Paenibacillus rhizosphaerae (Pr-LFI) and genes for d -tagatose-3-epimerase from Caballeronia fortuita (Cf-DTE) have been used for cloning and co-expression in Escherichia coli , developed a recombinant plasmid harboring pANY1-Pr-LFI/Cf-DTE vector. The recombinant co-expression system exhibited an optimum activity at 50 °C of temperature and pH 6.5 in the presence of Co 2+ metal ion which inflated the catalytic activity by 6.8 folds as compared to control group with no metal ions. The recombinant co-expressed system was stable up to more than 50 % relative activity after 12 h and revealed a melting temperature (T m ) of 63.38 °C exhibiting half-life of 13.17 h at 50 °C. The co-expression system exhibited, 4.93, 11.41 and 16.21 g/L of 6-DLS production from initial l -fucose concentration of 30, 70 and 100 g/L, which equates to conversion yield of 16.44 %, 16.30 % and 16.21 % respectively. Generally, this study offers a promising strategy for the biological production of 6-DLS from an inexpensive substrate l -fucose in slightly acidic conditions with the aid of co-expression system harboring Pr-LFI and CF-DTE genes.
研究领域:
生物技术
·
酶学
·
生化工程
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Juan Qiao,Qian Ma,Xiangfei Li,Li Qi
Expanding the category of redox-responsive monomers suitable for enzymolysis efficiency regulation and application to living biosystems is a prerequisite to complementing the fabrication of stimuli-responsive polymer nanoreactors. However, the development of redox-responsive monomers is severely limited by chemical oxidation and low biocompatibility. This work presents a protocol for overcoming this problem by the self-assembly of redox-responsive polymer nanoreactors containing segments of water-soluble methionine sulfoxide residues and poly(styrene-co-maleic anhydride-l-methionine), and by immobilizing α-l-fucosidase into the nanoreactors. These nanoreactors demonstrate highly selective responses to a mild redox triggered by H2O2 from the initial state (VO) to an oxidation state (VO1), and are reduced by methionine sulfoxide reductase A to mold the VO’ state. It resulted in significantly enhanced enzymolysis efficiency and maximal reaction rates 8.1-fold (VO) and 23.3-fold (VO1) higher than those of the free enzyme. Moreover, cell adhesion was evaluated by the highly selective determination of l-fucose on cell surfaces. Using a combination of chemical oxidation and enzymatic reduction, this work achieves reiterative enzymolysis efficiency regulation of polymer nanoreactors, which has great potential for the construction of redox-responsive nanoreactors and for monitoring cell adhesion.
研究领域:
聚合物化学
·
生物医学工程
·
生物化学
·
纳米技术
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shuangyu Shao,Xiali Si,Yingtao Zhang,Jun Li,Pengfei Tu,Qingying Zhang
Quality analysis of edible mushrooms based on polysaccharides is generally difficult due to their complicated structures and hard separation. Here, multiple fingerprint analysis of polysaccharides based on chromatographic and spectrometric techniques were developed, and then applied in comparative analysis of Auricularia heimuer (AH), Auricularia cornea (AC), Auricularia cornea ʻYu Muerʼ (ACY) and Tremella fuciformis (TF). Firstly, polysaccharides were obtained with the molecular weights between 1.783 × 10 6 and 6.774 × 10 6 Da. Then, complete hydrolysis by TFA and enzyme digestion by cellulase were employed and subsequently analyzed by HPLC-UV, GC–MS, HILIC-HPLC-ELSD and HILIC-HPLC-ESI − -HCD-MS/MS, and ATR-FT-IR were used to characterize the functional groups of intact polysaccharides. By chemometric analysis, differential markers of d -xyl, l -fuc, l -arb, d -glc, disaccharide and hexasaccharide were selected, and AC and ACY were proved to be same species from the viewpoint of polysaccharides firstly. Furthermore, the structures of oligomers with DPs of 2–8 and →4)- β - d -Glc p -(1→ unit with different contents were inferred by combinatory analysis of ESI − -MS/MS, glycosidic linkage, monosaccharide compositions and functional groups. In conclusion, the combinatory method of multiple fingerprint and pattern recognition is powerful not only for structural elucidation of polysaccharides, but also for quality analysis and species differentiation of edible mushrooms from the perspective of biological polysaccharides.
研究领域:
食品科学
·
分析化学
·
真菌学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·
IF 5.5
Tianqi Wang,Chunpei Li,Yu Ma,Hao Zhou,Xiaonan Du,Yingfeng Li,Shasha Long,Yifeng Ding,Guoping Lu,Weiming Chen,Yuanfeng Zhou,Lifei Yu,Ji Wang,Yi Wang
Aims Status epilepticus (SE) is the most common neurological emergency in pediatric patients. This study aimed to screen for prognostic biomarkers of SE in the cerebrospinal fluid (CSF) using metabolomics. Methods Ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was conducted to identify prognostic biomarkers in CSF metabolomics by comparing the poor outcome group ( N = 13) with the good outcome group ( N = 15) of children with SE. Differentially expressed metabolites were identified using Mann–Whitney U test corrected by Benjamini-Hochberg and partial least squares discriminant analysis (PLS-DA). Results The PLS-DA model identified and validated significant metabolic differences between the poor and good outcome groups of children with SE (PLS-DA with R 2 Y = 0.992 and Q 2 = 0.798). A total of 49 prognosis-related metabolites were identified. Of these metabolites, 20 including glutamyl-glutamine, 3-iodothyronamine, and L-fucose had an area under the curve (AUC) ≥ 80% in prognostic prediction of SE. The logistic regression model combining glutamyl-glutamine and 3-iodothyronamine produced an AUC value of 0.976, with a sensitivity of 0.863 and specificity of 0.956. Pathway analysis revealed that dysregulation of the citrate cycle (TCA) and arginine biosynthesis may contribute to poor SE prognosis. Conclusions This study highlighted the prognosis-related metabolomic disturbances in the CSF of children with SE and identified potential prognostic biomarkers. A prognostic prediction model combining glutamyl-glutamine and 3-iodothyronamine with high predictive value was established.
研究领域:
神经病学
·
儿科
·
代谢组学
·
临床化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1385
·
IF 7.5
Gong Jiaxin,Wei Feng,Wu Tianyu,Zhang Ningzhi,Zhang Yongqiao,Cui Zhaoqiang,Ge Junbo
Background Obesity-related cardiac injury is a serious global condition associated with excessive fat intake, which is strongly linked to chronic low-degrade inflammation. Pyroptosis, a pro-inflammatory form of cell death, has been implicated in obesity recently. L-Fucose (Fuc), a sulfated polysaccharide with anti-inflammatory and antioxidant properties, remains unexplored in the area of pyroptosis and obesity-related cardiac injury. Methods Six-week-old wide type C57BL/6 mice were subjected to high-fat diet (HFD) feeding for 20 weeks to induce obesity with or without Fuc gavaging, followed by assessment of metabolic related indicators. Echocardiography, histopathological analysis and enzymatic assays were used to assess cardiac function. The level of pro-inflammatory cytokines was detected by ELISA, qRT-PCR and CD68 staining. Pyroptosis-related protein including NLRP3, GSDMD, pro-caspase-1, cleaved-caspase-1, IL-1β, and ASC were evaluated by western blot. Oxidative stress was detected by ROS level. Cardiac mitochondrial structure was assessed by electron microscopy and mitotracker staining. Mitochondrial function was measured by mitochondrial membrane potential (MMP) and oxygen consumption rate (OCR) assay. Molecular docking and molecular dynamics (MD) simulations were conducted to look for the potential target of Fuc. Cellular thermal shift assay (CETSA) and western blot were used to investigate the interaction between Fuc and its target. Palmitic acid (PA) induced lipotoxicity model in AC16 cells was used to further confirm the protective effects of Fuc and its downstream signaling pathway against inflammation, pyroptosis and mitochondrial injury in vitro. Results In vivo, Fuc treatment alleviated obesity-related weight gain, hyperlipidemia, elevated systolic blood pressure and cardiac diastolic dysfunction. It also reduced the expression of pro-inflammatory cytokines and pyroptosis-related proteins, the level of oxidative stress, and mitochondrial abnormalities in the myocardium. Moreover, the vitro lipotoxicity model further confirmed the protective effect of Fuc. The molecular docking analysis identified TLR4 as the key target of Fuc. Fuc reduced the level of TLR4 and its downstream proteins MyD88 and p-NF-κB, while activating TLR4/MyD88/NF-κB pathway by TLR4 agonist Neoseptin3 reversed the protective function of Fuc in vitro. Conclusions These findings demonstrated that Fuc mitigated cardiac inflammation, pyroptosis and mitochondrial injury by inhibiting the TLR4/MyD88/NF-κB pathway, highlighting its potential as a therapeutic agent for obesity-associated cardiac injury.
研究领域:
心脏病学
·
分子生物学
·
免疫学
·
代谢性疾病
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Jie Bai,Yongchun Huang,Yuling Zhao,Lirong Zhang,Fuli Zhu,Yixizhuoma,Yuxin Weng,Shoude Zhang
The structural characterization of polysaccharides requires precise determination of their monosaccharide composition, including the differentiation of D- and L-configurations. Current analytical methods can identify monosaccharide types but often fail to distinguish between enantiomeric configurations, posing a significant challenge for accurate polysaccharide structural elucidation. This study introduces a robust, accurate, and reproducible ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) method to address this limitation. By utilizing ( S )-(−)-1-phenylethylamine (S-PEA) as a chiral derivatizing reagent, monosaccharide enantiomers are converted into diastereomers through the introduction of a new chiral center. This approach enables the simultaneous determination of D/L configurations for aldoses, amino sugars, alditols, and uronic acids, achieving excellent chromatographic baseline separation. Method validation demonstrated excellent linearity (R 2 > 0.9900) within the range of 2.5–160 μg/mL. The limits of detection (LOD) and quantification (LOQ) ranged from 0.04 to 0.11 μg/mL and 0.13–0.35 μg/mL, respectively, indicating high sensitivity. Accuracy was confirmed with recovery rates between 97.23% and 100.67%, while intra- and inter-day precision RSDs were below 3.54%. The method was successfully applied to characterize the monosaccharide composition of six plant-derived polysaccharides, demonstrating its efficacy in identifying both structural types and absolute configurations. These findings establish the proposed method as a valuable tool for advancing the comprehensive structural analysis of polysaccharides.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2026
·
IF 12.5
Qingxia Yuan,Zidong Liu,Yue Yao,Haiqiong Ma,Jiewen Fu,Xiang Shi,Jinying Huang,Yonghong Liu,Longyan Zhao
Safe, potent, and low-bleeding anticoagulants remain an unmet medical need. Here we report a homogeneous glycosaminoglycan (GAG), designated TPG, isolated from the brittlestar Trichaster palmiferus . TPG (30.3 kDa, 32% sulfate) is composed of an almost equimolar ratio of L-Iduronic acid (IdoA) and N -acetyl-D-galactosamine (GalNAc) together with minor D-glucosamine (GlcN), D-galacturonic acid (GalA), and D-galactose (Gal). These physicochemical properties are distinct from heparin, dermatan sulfate, and chondroitin sulfate. Using one- and two-dimensional NMR of its desulfated derivative, free-radical depolymerized fragments, and oligosaccharide fractions generated by partial N -deacetylation-deamination cleavage, we established that the polymer backbone is built from four repeating disaccharides: L-IdoA 2S3S -α-1,3-D-GalNAc 4S/6S -β-1,4-, L-IdoA 2S -α-1,3-D-GalNAc 4S/6S -β-1,4-, D-GalA-α-1,3-D-GalNAc 4S -β-1,4-, and D-GalNAc 4S -β-1,4-GlcN 0S/6S -α-1,3-. The IdoA 2S3S and GalA residues and the D-GalNAc 4S -β-1,4-GlcN 0S/6S -α-1,3- unit are rare in natural GAGs, rendering TPG resistant to chondroitinase ABC. NMR detected terminal Gal in desulfated TPG and large oligosaccharide fragments, but its connection pattern remains unclear. TPG prolongs clotting times by simultaneously blocking intrinsic factor Xase and potentiating HCII-mediated thrombin inhibition, and it achieves potent antithrombotic efficacy in vivo with virtually no bleeding, an advantage over enoxaparin. These findings establish a brittlestar GAG whose unusual sulfation pattern defines a new class of high-efficacy, low-bleeding anticoagulants.
✓ 已验证
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）