BIORESOURCE TECHNOLOGY
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2015
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IF 4.494
Yu-Cai He,Dan-Ping Zhang,Zhi-Cheng Tao,Yun Lu,Yun Ding,Feng Liu,Zheng-Zhong Zhu,Huan Rui,Gao-Wei Zheng,Xian Zhang
To reduce dependence on the expensive cofactor and effectively biotransform ethyl 4-chloro-3-oxobutanoate, l -glutamine and glycine were found to enhance the content of intracellular NADH and the reductase activity. Adding the mixture of 200 mM of l -glutamine and 500 mM of glycine to the reaction media, a 1.67-fold of reductase activity was increased over the control without the addition of the two compounds. Moreover, β-cyclodextrin (0.4 mol β-cyclodextrin/mol ethyl 4-chloro-3-oxobutanoate) was also added into this reaction media, and the biocatalytic activity of the whole-cell biocatalyst of Escherichia coli CCZU-K14 was increased by 1.34-fold than that without β-cyclodextrin. In this β-cyclodextrin–water media containing l -glutamine (200 mM) plus glycine (500 mM), ethyl ( S )-4-chloro-3-hydroxybutanoate (>99% ee ) could be obtained from 3000 mM ethyl 4-chloro-3-oxobutanoate in the yield of 98.0% after 8 h. All the positive features demonstrate the potential applicability of the bioprocess for the large-scale production of ethyl ( S )-4-chloro-3-hydroxybutanoate.
研究领域:
生物化学
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酶工程
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有机合成
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DOI
PubMed
高影响因子
Food and Bioprocess Technology
·
2026
·Vol. 19
·期 7
·346
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IF 5.6
Li Changhao,Liu Ruiqi,Li Na,Yang Lingfan,An Guangying,Tian Tian,Li Huina,Wang Guangxian,Wang Songlei
Wolfberry, a medicinal and edible plant rich in nicotinamide adenine dinucleotide (NADH), is noted for its antiaging and antioxidant properties. However, the trace levels and instability of NADH present significant detection challenges. To overcome the inherent limitations of traditional electrochemical linear peak fitting, three machine learning algorithms were introduced: random forest, support vector machine regression (SVR), and long short-term memory neural networks. This pioneering approach established a complex nonlinear relationship model between concentration and response current, effectively mitigating high-concentration linear distortion and interference constraints within the detection system. The Shapley additive prediction method (SHAP) was ultimately employed to quantify the contribution of each electrode potential to the prediction of response currents. This study developed an electrochemical biosensor based on a NbC@NC-ZIF-8/ADH heterojunction substrate, combined with a machine learning–based nonlinear modeling approach, achieving precise quantitative detection of NADH concentration in wolfberry. It exhibits a broad detection range from 1 μM to 1.5 mM, with a detection limit as low as 0.075 μM. The linear prediction model achieved R 2 = 0.976. After constructing a nonlinear model using the SVR machine learning algorithm, the NADH concentration detection accuracy improved to R 2 = 0.996, significantly enhancing detection precision. SHAP analysis indicated that the 0.264 V potential contributed most significantly to the model output. This study established a trace detection research framework encompassing “heterojunction material preparation–density functional theory analysis–nonlinear model construction–SHAP interpretability analysis,” providing a reliable solution for the rapid and accurate detection of NADH in wolfberry. It demonstrates broad application prospects in the field of bioanalysis.
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DOI
高影响因子
PHYTOMEDICINE
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2025
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IF 8.3
Yao-lei Ma,Xiao-wei Huo,Colin Wong,Feng-jie Zhou,Shan-ze Li,Han Zhang,Wei Lei
Background Although doxorubicin (DOX) is a highly efficient antineoplastic chemotherapeutic drug, it greatly increases the risk of heart damage. Salvianolic acid A (SAA), a water-soluble active component from traditional Chinese medicine Salvia miltiorrhiza Bunge, is shown to exert various cardioprotective effects. However, the potential of SAA in protecting DOX-induced cardiotoxicity (DIC) and its underlying mechanisms have yet to be elucidated. Purpose In the current study, we aimed to identify the targets and investigate the cardioprotective mechanism of SAA improving DIC. Methods we established DIC mice to evaluate the cardioprotective effects of SAA by pharmacodynamics, myocardial metabolomic and protomics analysis. Multipe protein-small molecule interaction strategies including surface plasmon resonance, microscale thermophoresis and cellular thermal shift assay, combined with target-depleted cell and animal models were applied for identifying potential targets of SAA. For clinical translation, we also investigated cardioprotective activities of SAA in DOX-treated lewis lung carcinoma-bearing mice. Results SAA significantly alleviated cardiomyocyte apoptosis and oxidative damage, and improved echocardiographic parameters in DIC mice. In addition, myocardium metabolomic and proteomics analysis revealed that SAA preserved hearts by modulating L-Glutamic acid, L-Aspartic acid, citrate and isocitrate and restoring glutamic-oxaloacetic transaminase 2 (GOT2) expression. With the help of multipe protein-small molecule interaction strategies, GOT2 was identified as one of the targets of SAA, and a strong affinity was characterized with a dissociation constant of 1.712 μM. SAA ameliorated DOX-induced oxidative damage, mitochondrial respiration suppression, mitochondrial membrane potential loss and NADH levels, which were validated in GOT2 knockdown H9C2 cells. In GOT2 depleted zebrafish, SAA did not display a protective effect against DIC, while in lewis lung carcinoma-bearing mice, SAA not only improved DIC, but also exerted combined anti-tumor effects with DOX. Conclusion SAA targets GOT2 to alleviate myocardial oxidative stress by regulating malate-aspartate NADH shuttle, thereby protecting against DIC. Our findings highlighted the therapeutic potential of activating GOT2 in mitigating DIC and the possibility of SAA and DOX-based combination therapy.
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PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2017
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IF 6.259
Yiqing Yang,You Yu,Xiaolu Li,Jing Li,Yue Wu,Jie Yu,Jingpeng Ge,Zhenghui Huang,Lubin Jiang,Yu Rao,Maojun Yang
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states. The PfNDH2 inhibitor exhibits excellent potency against both drug-resistant strains in vitro and parasite-infected mice in vivo via a potential allosteric mechanism. Furthermore, it was found that the inhibitor can be used in combination with dihydroartemisinin (DHA) synergistically. These findings not only are important for malarial PfNDH2 protein-based drug development but could also have broad implications for other NDH2-containing pathogenic microorganisms such as Mycobacterium tuberculosis.
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PubMed
高影响因子
2D Materials
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2023
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IF 5.5
Qiang Peng,Nian Jiang,Ling Qian,Wanqing Yue
Oxidation-derived nanoparticles (CDs/TiOx) of Ti3C2 were prepared for the first time by simple oxidation of Ti3C2. CDs/TiOx was a two-dimensional hybrid of amorphous carbon and titanium oxides with a lateral dimension of about 50 nm. H2O2 was used as the oxygenator and the reduction product was H2O, which was environmentally friendly and inexpensive. Carboxyl, carbonyl, and hydroxyl groups are formed naturally during the oxidation derivative process. The decreased size increases the specific surface area and provides the possibility for the abundant presence of functional groups. The oxidation process converts MXene from reducing to oxidizing and achieves the ability of the derivatives to mimic peroxidase. Compared with natural horseradish peroxidase, the Michaelis constant for H2O2 was 10-fold lower. A cascade catalytic reaction system of glucose oxidase with CDs/TiOx was constructed, and the generated H2O2 could be further used to catalyze the oxidation of NADH to NAD+. With the assistance of NAD+-dependent dehydrogenase, NADH could be restored to 95% of the initial level. This assay system can detect glucose levels scientifically and accurately in the range of 0.02-10 mM and remains viable after 20 cycles.
研究领域:
材料科学
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生物化学
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纳米技术
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酶工程
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分析化学
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产品关联
DOI
高影响因子
Materials Today Communications
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2019
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IF 1.859
Maruthupandy Muthuchamy,Thillaichidambaram Muneeswaran,Govindan Rajivgandhi,Quero Franck,Anand Muthusamy,Song Ji-Ming
In the present study, we report CuO and ZnO nanoparticles (NPs) synthesized through biological route using Camellia japonica plant leaf extract and their efficiency detection of cysteine and dihydronicotinamide adenine dinucleotide (NADH) in addition to their antimicrobial properties. Changes in absorption peak intensity in the presence of cysteine or NADH was assessed by UV–vis spectrophotometry. The spectrometric detection limit for the cysteine and NADH was found to be 5 and 10 μM, respectively, for both CuO and ZnO NPs. Good linear relationships with R 2 = 0.9727 for CuO and 0.9862 for ZnO NPs were obtained when plotting the absorbance as a function of cysteine and NADH concentrations at 290 and 301 nm, respectively. The present metal oxide (CuO and ZnO) NPs sensors were found to be useful for the detection of two biomolecules; namely cysteine and NADH. Furthermore, the CuO and ZnO NPs were found to be highly effective against gram positive ( Streptococcus pneumoniae , Bacillus subtilis ) and gram negative ( Escherichia coli , Salmonella typhimurium ) bacterial pathogens as well as fungal strains of Aspergillus flavus, Aspergillus fumigates, Aspergillus niger and Candida albicans . A minimum inhibition concentration of 100 μg/mL was observed for both NPs against bacterial and fungal pathogens. Consequently, the present investigation offers an environmentally friendly approach to synthesize CuO and ZnO NPs for biomolecule detection as well as antimicrobial and antifungal applications.
研究领域:
纳米生物学
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分析化学
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微生物学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2026
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IF 8.7
Jiaying Ai,Jiajun Yan,Yuxin Zhang,Fuping Lu,Shuhong Mao,Yixun Jiang,Lei Li,Hui-Min Qin
Chemical tethering NAD + to GfADH enhances enzyme-cofactor spatial proximity. • The application of conjugate and NOX reduced the NAD + demand by 13-fold. • The NAD + -GfADH conjugate and NOX were co-fixed via sequential recruitment. • Co-immobilization enhanced enzyme stability with improved cofactor regeneration. The green biomanufacturing of high-value compounds is limited by enzyme instability and cofactor dependence. Herein, we developed a tailored multi-module immobilization strategy that integrated cofactor tethering with sequential multi-enzyme co-immobilization to facilitate the efficient conversion of allitol into D-allulose catalyzed by the Gluconobacter frateurii -derived dehydrogenase (GfADH). In this strategy, nicotinamide adenine dinucleotide (NAD + ) was covalently tethered to the surface of GfADH via a flexible linker, creating an NAD + -GfADH conjugate. Coupling the conjugate with NADH oxidase (NOX) established an efficient cofactor self-regenerating system, reducing the external NAD + demand by 13-fold. Furthermore, this conjugate was encapsulated within hybrid nanoflowers, thereby improving its reusability. To facilitate cofactor transfer, NOX was directionally recruited and colocalized with GfADH using the SpyTag/SpyCatcher system. The co-immobilized enzyme exhibited a high D-allulose yield of 88.7% from 110 mM allitol and retained 85.0% of its initial activity after 6–8 cycles. This work provides a valuable integrated strategy for cofactor regeneration and enzyme stabilization in cofactor-dependent biosynthesis. Download: Download high-res image (169KB) Download: Download full-size image
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PubMed
高影响因子
CHINESE JOURNAL OF CATALYSIS
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2024
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IF 15.7
Jiali Liu,Huicong Dai,Xin Liu,Yiqi Ren,Maodi Wang,Qihua Yang
Biocatalytic reduction is extensively employed in chemical and pharmaceutical industries due to its notable advantages including high activity, selectivity and mild reaction conditions, however, the stoichiometric use of the expensive NADH (reduced form of nicotinamide adenine dinucleotide) hinders its widespread application. Despite the persisting challenges of low charge separation efficiency and limited solubility of organic substrates in aqueous phase, in situ photocatalytic NADH regeneration remains a promising solution. Herein, we report the construction of an enzyme-photo-coupled catalytic system in Pickering emulsion droplet, which was stabilized by a charge separation and transfer modulated photocatalyst. The photocatalyst integrated with visible light driven conjugated polymer, TiO 2 and electron mediator greatly enhanced the cascade electron transfer from photocatalyst to NAD + . Consequently, NADH production rate over the integrated photocatalyst reaches as high as 2.4 mmol·g −1 ·h −1 under visible light irradiation, 12 folds higher than the corresponding physical mixture. Furthermore, the enzyme-photo-coupled catalytic system was constructed with alcohol dehydrogenase/NAD + confined in the emulsion droplet and photocatalyst assembled at the oil-water interface. The photoactive emulsion continuously catalyzed the n -butyaldehyde reduction to accumulate 16.1 mmol·L −1 butanol, equivalent to 14 cycles for NADH regeneration under visible light irradiation. The primary result demonstrates the potential application prospect of Pickering emulsion in enzyme-photo-coupled catalysis due to the facilitated charge transfer from photocatalyst to NAD + and fast mass diffusion attributed to the large interfacial area of water and oil.
研究领域:
催化
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化学工程
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生物技术
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材料科学
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产品关联
DOI
高影响因子
Algal Research-Biomass Biofuels and Bioproducts
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2024
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IF 4.6
Min Li,Zhen-Fang Shang,Zhi-Jing Ni,Hui-Jun Zhao,Qian Lei,Zhao-Jun Wei
Auxenochlorella pyrenoidosa 's industrial utility is closely associated with the concentration of high-value products. This study focuses on the effects of cinnamic acid (CA) and its derivatives, which known as secondary metabolites in higher plants and effective plant growth regulators, on the growth and metabolic profiles of A. pyrenoidosa . It was discovered that CA and its derivatives significantly enhance the biomass of A. pyrenoidosa under conditions of 10 mg/L over 48 h or 100 mg/L over 120 h. Cells treated with 10 mg/L CA exhibited lower oxidative stress and maintained robust metabolic activity. Metabolic pathways, including those for carbohydrates, lipids, small peptides, and cofactors, were stimulated, leading to the accumulation of a wide array of bio-products, notably high-value products such as α-linolenic acid, cis-4,7,10,13,16,19-docosahexaenoic acid (DHA), nicotinamide adenine dinucleotide plus hydrogen (NADH), glutathione, and vitamins B2/B3. This study demonstrates that CA and its derivatives are good nutritional enhancers for cultivating A. pyrenoidosa , highlighting their potential for broad application in biotechnological industries.
研究领域:
生物技术
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微生物学
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代谢组学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yuangui Tang,Chenyun Dai,Huihui Yang,Xian Yang,Ziyu Chen,Jinxiu Dou,Liuxu Zhang,Tao Bai,Junfang Zheng
Non-histone proteins localized in membrane, cytosol and nucleus are lactylated to promote tumor progression. However, whether mitochondrial proteins undergo lactylation and contribute to tumor progression remains unexplored. Here, we identified multiple lactylated mitochondrial proteins in human renal cell carcinoma (RCC) cells using lactylome profiling. Among these, malate dehydrogenase 2 (MDH2)–the only lactylated protein in the tricarboxylic acid (TCA) cycle–emerged as a key target, with K239 as its lactylation site. MDH2 K239la levels are regulated by KAT8 and SIRT3. Under low-glucose, high-lactate conditions mimicking the tumor microenvironment, MDH2 K239la elevated the NADH/NAD + ratio to drive ATP production and boosted NADPH generation to reduce ROS. This enables cells to alleviate oxidative stress, sustain mitochondrial function, and promote RCC malignancy in vitro and in vivo . Mechanistically, MDH2 K239la enhances MDH2 enzymatic activity and strengthens its interaction with the citrate transporter SLC25A1. This facilitates citrate efflux, fueling IDH1-dependent NADPH production when lactate serves as an energy source. Collectively, we unveil a lactylation-dependent mechanism that reprograms mitochondrial metabolism to confer oxidative stress resistance and drive RCC progression. Targeting mitochondrial proteins lactylation, exemplified by MDH2 K239la , represents a promising therapeutic strategy for RCC.
研究领域:
癌症生物学
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生物化学
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细胞生物学
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分子生物学
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代谢工程
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
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2024
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IF 8.5
Yicheng Ren,Quan Ma,Dong Li,Yanpei Chen,Qinyang Cheng,Zisheng Luo
Fluctuations in energy status are critical physiological factors influencing postharvest fruit quality. However, the role of autophagy, a stress-resistant biological process, in regulating postharvest fruit energy status remains unclear. In this study, we treated strawberry fruit with the autophagy inhibitor hydroxychloroquine (HCQ) to investigate the role of autophagy in maintaining energy status. The results demonstrated that HCQ treatment inhibited autophagosome formation, reducing relative autophagic activity by 73 % on day 6. HCQ treatment also reduced the energy charge and the NADH/NAD + ratio by 5 % and 61 %, respectively, on day 2. Corresponding to the decline in energy status, HCQ treatment led to a reduction in cytochrome C oxidase (CCO) and succinate dehydrogenase (SDH) activities by 47.48 % and 56.34 %, respectively, on day 3. Additionally, fluctuations in energy charge led to abnormalities in ripening and decreased stress resistance in autophagy-inhibited fruit. In conclusion, this study provides evidence that autophagy-mediated energy charge sustainability mitigates postharvest quality deterioration in fruit.
研究领域:
植物生理学
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采后生物学
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分子生物学
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DOI
PubMed
高影响因子
Inorganic Chemistry Frontiers
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2024
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IF 6.1
Xuwen Da,Yunli Xu,Lei Wang,Xiulian Liu,Yatong Peng,Yao Wu,Wanpeng Zhou,Wentao Wang,Xuesong Wang,Qian-Xiong Zhou
Traditional photodynamic therapy (PDT) is almost ineffective against deeply seated tumors due to the limited penetration depth of external light. The development of chemiexcited PDT is promising to address this issue, but it is still challenging to construct simple, efficient and targeted chemiexcited PDT systems. In this work, CPPO (bio(3,5,6-trichloro-2-n-pentyloxycarbonylphenyl) oxalate) and [Ru(phen)2(PIP-OCH3)](PF6)2 (Ru3, where phen = 1,10-phenanthroline, PIP-OCH3 = 2-(4-methoxy phenyl)-1Himidazo[4,5-f][1,10]phenanthroline) with efficient photo-catalytic NADH oxidation were co-encapsulated with DSPE-PEG 2000 to form Ru3/CPPO@PEG nanoparticles (NP3). Once internalized by cancer cells, Ru3 can be excited by the chemical energy produced by the reaction between CPPO and endogenous H2O2. The subsequent oxidation of intracellular NADH and generation of H2O2 in situ by excited Ru3 will further promote the sustained occurrence of chemical reaction, realizing a self-enhanced chemiexcited PDT. NP3 could effectively deplete intracellular NADH, inhibit ATP synthesis, increase H2O2 content, and produce reactive oxygen species (ROS) within cancer cells, thus exhibited efficient chemiexcited PDT activity against various cancer cells. Notably, minimal cytotoxicity was observed towards normal cells. Good therapeutic effects against subcutaneously implanted and lung metastatic tumors were also observed for NP3. The current findings may provide new sights for development of novel chemiexcited PDT.
研究领域:
光动力疗法
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癌症研究
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纳米技术
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生物化学
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药学
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）