INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
·
IF 7.7
Guocong Luo,Zhaolin Huang,Yingying Zhu,Jiajun Chen,Xiaodong Hou,Dawei Ni,Wei Xu,Wenli Zhang,Yijian Rao,Wanmeng Mu
Lacto-N-neotetraose (LNnT), a representative oligosaccharide found in human milk, has been previously examined for its beneficial traits. However, the LNnT titer is limited by the efficient glycosyltransferase pathway, particularly with respect to the catalysis of rate-limiting steps. As data on the crystal structure of the key enzyme required for synthesizing LNnT are lacking, the synthesis of LNnT remains an uncertainty. Here, for the first time we report the three-dimensional structure of a bacterial β-1,4-galactosyltransferase, Aaβ4GalT, and analyze the critical role played by residues in its catalytic efficacy. Guided by structural insights, we engineered this enzyme to enhance its catalytic efficiency using structure-guided tunnel engineering. The mutant enzyme L5 (K155M/H156D/F157W/K185M/Q216V) so produced, showed a 50-fold enhancement in catalytic activity. Crystal structure analysis revealed that the mechanism underlying the improvement in activity was of the swing door type. The closed conformation formed by dense hydrophobic packing with Q216V-K155M widened and permitted substrate entry. Our results show that altering the tunnel conformation helped appropriately accommodate the substrate for catalysis and provide a structural basis for the modification of other glycosyltransferases.
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ENZYME AND MICROBIAL TECHNOLOGY
·
2024
·
IF 3.4
Jiehu Liu,Runtian Huo,Huixian Fu,Shiheng Chen,Xueyi Qiao,Bo Xu,Zhaoyuan Zhang,Jing Wu,Lingqia Su
β-nicotinamide mononucleotide (β-NMN) is a key precursor of nicotinamide adenine dinucleotide, and becomes attractive in the nutrition and health care fields, but its enzymatic synthesis is expensive. In this study, a six-enzyme cascade catalytic system was constructed to produce β-NMN. Using D-ribose and nicotinamide as substrates, the β-NMN yield reached 97.5 % catalyzed by purified enzymes. Then, after knocking out the genes encoding proteins that consume β-NMN in E. coli BL21(DE3), the similar β-NMN yield, 97.2 %, using the crude enzymes could be also obtained. After that, β-NMN synthesis was performed under increased substrate concentration, and 'modular' crude enzymes cascade catalytic reaction system was proposed to reduce the inhibition of polyphosphate on ribose-phosphate diphosphokinase activity, and the β-NMN yield reached 78.4 % at 10 mM D-ribose, which is 1.82 times of that in 'one-pot' reaction and represents the highest β-NMN preparation level with phosphoribosylpyrophosphate as the core reported till now.
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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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2024
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IF 2.5
Hangyu Shen,Wenhui Liu,Yun Dou,Yongxin Lu,Chunling Zhang,Xiaoying Wang,Fangong Kong,Shoujuan Wang
In general, Cu(II) is the critical factor in catalyzing reactive oxygen species (ROS) production and accelerating amyloid-β (Aβ) oligomer formation in Alzheimer's disease (AD). Natural chelating agents with good biocompatibility and appropriate binding affinity with Cu(II) have emerged as potential candidates for AD therapy. Herein, we tested the capability of guluronic acid disaccharide (Di–GA), a natural chelating agent with the moderate association affinity to Cu(II), in inhibiting ROS production and Aβ oligomer formation. The results showed that Di−GA was capable of chelating with Cu(II) and reducing ROS production, even in solutions containing Fe(II), Zn(II), and Aβ. In addition, Di−GA can also capture Cu(II) from Cu−Aβ complexes and decrease Aβ oligomer formation. The cellular results confirmed that Di−GA prevented SH−SY5Y cells from ROS and Aβ oligomer damage by reducing the injury of ROS and Aβ oligomers on cell membrane and decreasing their intracellular damage on mitochondria. Notably, the slightly higher efficiency of Di–GA in chelating with Cu(I) than Cu(II) can be benefit for its in vivo applications, as Cu(I) is not only the most active but also the special intermediate specie during ROS production process. All of these results proved that Di–GA could be a promising marine drug candidate in reducing copper-related ROS damage and Aβ oligomer toxicity associated with AD.
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INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
·
IF 5.3
Yibo Pan,Xiaoqiang Ma,Jianxia Sun,Weibin Bai
Anthocyanins, one of the important water-soluble pigments, are sensitive to environmental factors, which limits the application of anthocyanins in food field. In order to overcome this limitation, double Pickering emulsions stabilized by β-cyclodextrin were developed. The optimum preparation conditions of the emulsions were determined firstly and the performance and structure of emulsions were investigated. Results showed that the optimum preparation conditions of emulsions were the ratio of (W 1 /O): W 2 = 6:4 and 4 % β-cyclodextrin concentration. Optical microscope and confocal laser scanning microscope results confirmed that β-cyclodextrin adsorbed onto the surface of droplets forming stable double Pickering emulsions structure. In vitro gastrointestinal digestion experiments proved that double Pickering emulsions played a controlled-release effect in the small intestine. Rheological analysis proved that the emulsions exhibited elastic properties and demonstrated shear thinning behavior. The emulsions showed excellent stability under centrifugation and thermal conditions. These findings will promote anthocyanins’ application in daily diet.
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JOURNAL OF POLYMER SCIENCE
·
2024
·
IF 3.9
Na Liang,Caixia Yan,Zhenrong Liu,Wenlong Hu,Kun Jiang,Gang Li,Shaoping Sun
To improve the therapeutic efficiency of paclitaxel (PTX) and reduce its toxicity to normal tissues, a novel hydroxypropyl-β-cyclodextrin (HP-β-CD) derivative has been designed and developed. The polymer (bio-HP-β-CD(NAC)-PLA) is synthesized by modifying HP-β-CD with polylactic acid, cysteine, and biotin. Using bio-HP-β-CD(NAC)-PLA as the carrier, a PTX-loaded nanoparticulate system is developed by a modified emulsion solvent evaporation method. The optimized drug-loaded nanoparticles are obtained with a mean diameter of 162.4 nm and drug loading of 16.1%. In vitro drug release study exhibits that PTX is released in a redox-dependent manner. Cellular uptake study suggests that the bio-HP-β-CD(NAC)-PLA nanoparticles can be specifically taken up by MCF-7 cells via the biotin receptor-mediated endocytosis. In vitro and in vivo anticancer efficacy evaluations demonstrate the superior antitumor activity and negligible toxicity of the PTX-loaded nanoparticles. It can be concluded that the proposed polymer bio-HP-β-CD(NAC)-PLA offers a promising drug delivery system for targeted delivery and controlled release of PTX. Graphical
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TOXICOLOGY LETTERS
·
2025
·
IF 2.9
Chenyu Xiao,Qianru Li,Meiqi Li,Yongshu Han,Hubin Xu,Haimin Jiang,Suer Zhang,Zhen Jin,Leilei Gao
Iodoacetamide (IAcAm) is a harmful disinfection by-product. Studies have demonstrated that IAcAm can produce toxic effects in various tissues; however, its effect on female reproductive function remains unclear. To explore the effects of IAcAm on ovaries, we constructed a female mouse IAcAm toxicity model of free drinking model. The findings indicated that IAcAm exposure for five weeks did not affect the body growth of mice but increased the ovary/body weight ratio. At the tissue level, the numbers of atretic follicles increased. After the exposure, ovarian and blood samples were collected for analysis. IAcAm exposure caused changes in serum sex hormone levels, with an increase in follicle-stimulating hormone concentration(follicle-stimulating hormone) and a decrease in anti-Müllerian hormone concentration (anti-Müllerian hormone). Subsequent investigations revealed that IAcAm activated the transforming growth factor-β (TGF-β) signaling pathway and promoted ovarian fibrosis in mice. Simultaneously, IAcAm stimulated the granulosa cell apoptosis pathway and promoted granulosa cell apoptosis. Moreover, IAcAm interfered with mitochondrial function and increased reactive oxygen species, leading to a decrease in oocyte developmental potential. In conclusion, IAcAm exposure causes ovarian inflammation and leads to mitochondrial dysfunction in oocytes, affecting follicle maturation and reducing oocyte quality.
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MEDICINAL CHEMISTRY RESEARCH
·
2024
·
IF 2.6
Cheng Wenhui,Zhang Yuejuan,Chen Cheng,Gao Lei,Lv Yuwei,Yu Dian,Chen Bin,Wan Yi
The production of carbapenemases is a significant mechanism contributing to carbapenem resistance in Enterobacteriaceae . Among these carbapenemases, OXA-48 presents a distinct challenge and threat, as most β-lactamase inhibitors do not effectively inhibit its activity. In this study, we investigated the inhibitory potential of α-mangostin against OXA-48 with an IC 50 value of 0.52 μM. Enzyme activity assays demonstrated that α-mangostin inhibited OXA-48 reversibly through a non-competitive and dose-dependent inhibition mode. The docking analysis revealed that the 7-hydroxyl group of α-mangostin formed hydrogen bonds with Thr197 and Trp222, whereas the 5-hydroxyl group and the 4-carbonyl group interacted with Lys116 and Met115. Our study indicates that α-mangostin exhibits significant inhibition against OXA-48 and holds promise as a potential compound for the development of β-lactamase inhibitors.
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FOOD CHEMISTRY
·
2024
·
IF 8.5
Xian Qu,Yahui Ji,Jieyi Long,Donglin Zheng,Zhonghui Qiao,Yue Lin,Chang Lu,Yifa Zhou,Hairong Cheng
The β-1,6-glucans from Lentinus edodes have a variety of biological activities. However, the research on extraction and separation of β-1,6-glucans from L. edodes is limited and the yield is low. In the present study, we obtained the high-yield and -purity β-1,6-glucans (ALEPA) from L. edodes by using a sequential extraction and separation process, which is simple and suitable for industrialization . ALEPA significantly promoted the proliferation of splenic T lymphocytes and enhanced the phagocytosis activity of peritoneal macrophages in vivo . 16S rRNA sequencing results showed that ALEPA significantly increased the α diversity of gut microbiota and upregulated the relative abundances of short chain fatty acids (SCFAs)-producing bacterial species. Consistently, the SCFAs in the cecum of mice were upregulated. On a mechanical level, we found that the immunomodulatory effect of ALEPA depended on gut microbiota. Collectively, ALEPA is a promising functional food ingredient that regulates gut microbiota and enhances immune function.
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Food Frontiers
·
2024
·
IF 7.4
Lu An,Wenbo Wang,Jihao Chu,Lin An,Bingyu Geng,Xueqi Fu,Jing Chen,Junfeng Ma
Alzheimer's disease (AD) poses a significant global health challenge, primarily characterized by the aggregation of β-amyloid (Aβ) peptides and associated oxidative stress. Given the lack of effective AD drugs, we investigated the effects of Lycium barbarum polysaccharide (LBP), a water-soluble polysaccharide from goji berries, on Aβ scavenging, aggregation, and Aβ-induced toxicity using the transgenic AD nematode. LBP treatment delayed paralysis, mitigated Aβ-induced chemotaxis deficits, and reduced Aβ 1–42 deposition and oligomer formation in AD nematodes. Furthermore, LBP supplementation alleviated Aβ-induced oxidative stress and improved oxidative stress resistance through the insulin/insulin growth factor 1 (IGF-1) signaling (IIS) pathway. Evaluation of the Aβ clearance pathway revealed that LBP attenuated Aβ toxicity by increasing proteasome activity rather than lysosomal levels. Basic physiological assessments further indicated that LBP was non-toxic in vivo and promoted nematode health. Our findings suggest that LBP ameliorates AD-like symptoms in nematodes by activating the IIS pathway to reduce oxidative stress and enhancing proteasomal activity to clear Aβ aggregates, providing a new theoretical basis for considering LBP as a promising therapeutic drug for AD and related oxidative stress complications.
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Biomass Conversion and Biorefinery
·
2024
·
IF 3.5
Yang Shuanghao,Feng Ruirui,Sun Bo,Lu Meizi,Zhao Xingchu,Shen Qirong,Wan Qun
Corncob, as an agricultural waste rich in hemicellulose, plays a crucial role in the effective utilization for biomass conversion and biorefinery. Here, we report a thermophilic GH11 xylanase (Xyn11B) and a β-xylosidase (Xyl43B) in the compost metatranscriptome database, with optimal temperature of 75 ℃ and 70 ℃, respectively, utilized for the synergistic degradation of corncob. Xyn11B consists of a catalytic domain (CD) and a carbohydrate-binding module 60 (CBM60). After deleting CBM60, the T m of the remaining CD Xyn increased by 2.4 ℃ and the half-life at 80 ℃ increased threefold. After 10-h hydrolysis on the NaOH-treated corncob using Xyn11B and CD Xyn , the conversion yield reached 78 and 94 mg sugar/g raw corncob, respectively. Interestingly, in the absence of alkali pretreatment, the conversion yield can reach 107 mg sugar/g raw corncob using 0.1% (mg enzyme/mg corncob) Xyn11B, which is two times higher than that of CD Xyn . Our analysis shows that CBM60 can reduce the non-catalytic adsorption to lignin, which increases the capability of the full-length enzyme to hydrolyze hemicellulose without alkali pretreatment. Furthermore, synergistic hydrolysis with both 0.1% Xyn11B and 0.1% Xyl43B considerably elevates the conversion yield to 296 mg sugar/g raw corncob, which is 2.8-fold higher than that achieved using Xyn11B alone, and comparable to the enzymatic effect observed with the combination of CD Xyn and Xyl43B in alkali pretreatment. Our strategy demonstrates a good example of green hydrolysis of lignocellulosic biomass using enzymes without chemical pretreatment.
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JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY
·
2011
·Vol. 71
·期 1
·207-213
·
IF 1.22
Wang Ting,Li Bin,Si Hongyan,Lin Li,Chen Li
A solid state eugenol/β-cyclodextrin inclusion complex (EG/β-CD) was prepared by lyophilization method and characterized by Powder X-ray Diffraction (XRD) and Fourier Fransform Infrared Spectroscopy (FTIR). UV–Vis spectrometer was used to determine the EG content encapsulated in the complex. In order to estimate the release characteristics of the EG/β-CD powder, Avrami’s equation and Thermogravimetric (TG) analyzer were, respectively, used. The loss percentage of EG was no more than 10 wt% for 4 week exposing at 25 °C and 75% humidity, and the release of EG is controlled by a combination mechanism of diffusion and first-order mode. TG results not only proved the thermo stability of the EG in EG/β-CD complex, but also clarified the thermal decomposition behaviors of the EG/β-CD. The antibacterial activity of the EG/β-CD complex was investigated using agar cup-plate diffusion method and bacterial strains of Escherichia coli , Salmonella paratyphi B, and Staphyloccocus aureus were used. The results indicated that EG/β-CD had a selective antimicrobial active against Escherichia coli .
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Journal of Environmental Chemical Engineering
·
2024
·
IF 7.4
Miaomiao Zhu,Qinwei Fan,Yixin Zhang,Shuang Chen,Wenxuan Cao,Ranhua Xiong,Chaobo Huang,Haifeng Lu,Wenjing Ma
In order to deal with the environmental pollution caused by complex oily wastewater, it is necessary to develop filtration membrane materials. However, significant challenges such as poor effect of emulsion separation, limited functionality, and susceptibility to membrane fouling require urgent resolution. Here, we successfully prepared a β-hydroxyl iron oxide/polydopamine-polyethylenimine/polyacrylonitrile (β-FeOOH/PDA-PEI/PAN) nanofiber membrane for treatment of complex wastewater by growing PDA-PEI on a blow-spinning PAN nanofiber membrane and decorating the membrane with β-FeOOH. The porous structure and the large number of hydrophilic groups greatly increase the hydrophilicity of the membrane and give the membrane high permeation fluxes (11531.26 L m −2 h −1 ) for surfactant-free kerosene-in-water emulsion. The loaded β-FeOOH nanorods increase the roughness of the membrane surface, which enhances the underwater superoleophobic ability of the membrane, and promotes the demulsification of the emulsion and makes it have high separation efficiency of 99.48 % for surfactant-stabilized kerosene-in-water emulsion. In addition, the β-FeOOH/PDA-PEI/PAN also exhibited high organic dye removal efficiency (99.38 %) due to the presence of β-FeOOH. The synergistic effect of low oil adhesion and photocatalysis enhances the antifouling and self-cleaning performances of the material. Significantly, the multifunctional membrane also shows exceptional oil/water separation ability and good stability. The presented synergistic strategy of β-FeOOH/PDA-PEI/PAN membrane materials represents a prospective candidate for the treatment of complex wastewater.
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