ACS Sustainable Chemistry & Engineering
·
2025
·
IF 7.3
Ran Wang,Wei Song,Hangyuan Xu,Jian Wen,Wanqing Wei,Zhaoyang Chen,Guipeng Hu,Cong Gao,Xiaomin Li,Jia Liu,Jing Wu
l-Asparagine (l-Asn) is an important amino acid with broad applications in food, medicine, fine chemicals, and environmental protection. However, its industrial production is limited by the high cost of raw materials and the low catalytic efficiency of enzymes. In this study, a three-enzyme cascade pathway (FDN) was designed to produce l-Asn, using fumaric acid as the raw material. Within this pathway, EcAsnA was identified as the rate-limiting enzyme and was subsequently engineered using a product rescue strategy to reduce product inhibition by opening the closed gate. The optimal mutant, L109 K/K58R, exhibited a 6.61-fold reduction in product inhibition and a 4.24-fold improvement in catalytic efficiency. This mutant was then integrated into Escherichia coli along with the other two enzymes to construct the optimal recombinant strain E. coli 17. Using diatomite-glutaraldehyde cross-linking immobilized E. coli 17 as a biocatalyst, 267.74 g of l-Asn (with 5.35 g·L–1·h–1 STY, > 99% ee) was produced across 50 batch feedings in 1 L reaction volume. The purity of l-Asn exceeded 99% after isolation and purification. This study demonstrates the effective integration of cascade reaction design, enzyme engineering, and cell immobilization, providing a promising approach for synthesizing high-value products from cost-effective substrates.
研究领域:
生物化学
·
酶学
·
合成生物学
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产品关联
DOI
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Li Na,Wang Tianyi,Zhang Huiying,Li Xiao,Bai Haochen,Lu Ning,Lu Kaizhi
Objective: This investigation sought to delineate the causal nexus between plasma glutamine concentrations and leukemia susceptibility utilizing bidirectional Mendelian Randomization (MR) analysis and to elucidate the metabolic ramifications of asparaginase therapy on glutamine dynamics in leukemia patients.Methods: A bidirectional two-sample MR framework was implemented, leveraging genetic variants as instrumental variables from extensive genome-wide association studies (GWAS) tailored to populations of European descent. Glutamine quantification was executed through a rigorously validated Liquid Chromatography-Mass Spectrometry/Mass Spectrometry (LC-MS/MS) protocol. Comparative analyses of glutamine levels were conducted across leukemia patients versus healthy controls, pre- and post-asparaginase administration. Statistical evaluations employed inverse variance weighted (IVW) models, MR-Egger regression, and sensitivity tests addressing pleiotropy and heterogeneity.Results: The MR findings underscored a significant inverse association between glutamine levels and leukemia risk (IVW p = 0.03558833), positing lower glutamine levels as a contributory factor to heightened leukemia susceptibility. Conversely, the analysis disclosed no substantive causal impact of leukemia on glutamine modulation (IVW p = 0.9694758). Notably, post-asparaginase treatment, a marked decrement in plasma glutamine concentrations was observed in patients (p = 0.0068), underlining the profound metabolic influence of the therapeutic regimen.Conclusion: This study corroborates the hypothesized inverse relationship between plasma glutamine levels and leukemia risk, enhancing our understanding of glutamine’s role in leukemia pathophysiology. The pronounced reduction in glutamine levels following asparaginase intervention highlights the critical need for meticulous metabolic monitoring to refine therapeutic efficacy and optimize patient management in clinical oncology. These insights pave the way for more tailored and efficacious treatment modalities in the realm of personalized medicine.
研究领域:
医学
·
遗传学
·
代谢组学
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产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2019
·Vol. 43
·期 8
·3323-3331
·
IF 3.069
Xi Wang,Tian Gao,Mian Yang,Jie Zhao,Feng-Lei Jiang,Yi Liu
L-Asparagine, a common amino acid, is a cost-effective and ideal precursor for carbon dots because of its high nitrogen content and its abundance in nature. By using L-asparagine as a biocompatible precursor, fluorescent nitrogen-doped carbon dots (A-CDs) were prepared by a one-pot microwave-assisted method. Then, a reasonable structure for A-CDs was put forward, which confirmed that unconjugated small molecules could transform into carbon dots with the sp2 core, and was helpful in the discussion of the photoluminescence mechanism. It was concluded that the photoluminescence origin of A-CDs was from the graphite-like structure and surface defects. The A-CDs showed high stability in strong ionic solutions and negligible cytotoxicity even when the incubation concentration was up to 800 μg mL−1. Long-time bioimaging tests suggested that A-CDs have great potential for use in a wide variety of biological applications.
研究领域:
材料科学
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生物医学工程
·
化学
✓ 已验证
DOI
高影响因子
RSC Advances
·
2015
·Vol. 5
·期 91
·74977-74985
·
IF 3.84
Xin Xiao,Shunheng Tu,Chunxia Zheng,Huan Zhong,Xiaoxi Zuo,Junmin Nan
Large-scale synthesis of nanosized β-Bi2O3 is a significant challenge due to its metastable state. A facile L-asparagine-assisted reflux–calcination route was successfully developed for the large-scale preparation of β-Bi2O3 micro/nanostructures under mild conditions (low temperature, atmospheric pressure, and wide temperature windows). The composition, phase structure, morphology, surface area, and photoabsorption properties of as-synthesized β-Bi2O3 and its precursor were systematically characterized. The phase transformation conditions and possible formation mechanism of flower-like β-Bi2O3 were discussed. It is found that with a simple reflux process under atmospheric pressure at 100 °C, uniform monodisperse bismuth–asparagine complex microspheres with average diameters of ∼500 nm were produced and flower-like β-Bi2O3 micro/nanostructures were then conveniently obtained after precursor calcination at temperatures ranging from 340 °C to 420 °C. A surface CO32− coordination effect introduced from L-asparagine explained the formation of stabilized β-Bi2O3 at low temperatures (up to 420 °C). The as-synthesized β-Bi2O3 shows excellent photocatalytic activity toward the degradation of 4-phenylphenol under visible-light irradiation, which is 3.7 and 21.4 times faster than the removal rates of β-Bi2O3 nanospheres and a commercial β-Bi2O3, respectively, and allows for the elimination of 93.2% total organic carbon after 60 min of irradiation. In addition, the photogenerated reactive species were identified by radical scavenger experiments and electron paramagnetic resonance spectroscopy, and a possible visible-light-induced photocatalytic mechanism was then proposed.
研究领域:
材料科学
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环境科学
✓ 已验证
产品关联
DOI
高影响因子
AGING CELL
·
2024
·
IF 8
Ting Luo,Liusha Zhao,Chenxi Feng,Jinhua Yan,Yu Yuan,Haiyang Chen
The age-associated decline in intestinal stem cell (ISC) function is a key factor in intestinal aging in organisms, resulting in impaired intestinal function and increased susceptibility to age-related diseases. Consequently, it is imperative to develop effective therapeutic strategies to prevent ISC aging and functional decline. In this study, we utilized an aging Drosophila model screening of amino acids and found that asparagine (Asn), a nonessential amino acid in vivo, exhibits its profound anti-aging properties on ISCs. Asn inhibits the hyperproliferation of aging ISCs in Drosophila , maintains intestinal homeostasis, and extends the lifespan of aging flies. Complementarily, Asn promotes the growth and branching of elderly murine intestinal organoids, indicating its anti-aging capacity to enhance ISC function. Mechanistic analyses have revealed that Asn exerts its effects via the activation of the autophagic signaling pathway. In summary, this study has preliminarily explored the potential supportive role of Asn in ameliorating intestinal aging, providing a foundation for further research into therapeutic interventions targeting age-related intestinal dysfunction.
研究领域:
衰老
·
干细胞生物学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2019
·
IF 8.456
Juan Qiao,Junfang Jiang,Lili Liu,Ji Shen,Li Qi
The challenge for polymeric enzyme reactors at present is to selectively control the enzymolysis rate in complex conditions. Additionally, the fabrication methodology is hindered by complex processes, especially for achieving diverse stimuli responsiveness and functions. Here, we reported a kind of pH-sensitive polymer, poly(styrene-co-maleic anhydride-acrylic acid) (PS-MAn-AA)-based hybrid enzyme reactor. It comprised magnetic nanoparticles and a pH-sensitive PS-MAn-AA porous polymer membrane made by breath figure method. The enzyme l-asparaginase (l-ASNase) could covalently bond on the surface of the pH-sensitive porous polymer membrane (pH-PPM), and the resultant enzyme reactor was characterized by Fourier transform infrared spectroscopy and vibrating sample magnetometer. The apparent Michaelis–Menten constants (Km and Vmax) of the l-ASNase enzyme reactor at different pH values were determined by a chiral ligand-exchange capillary electrophoresis method with l-asparagine as the substrate. The Vmax value of the l-ASNase enzyme reactor (0.67 mM/min) was almost 3-fold of that of the free l-ASNase (0.23 mM/min) at pH 8.2. Its ability to precisely control the enzymolysis rate in complex conditions is triggered primarily by the pH of the buffer solution, allowing controlled enzymatic reactions and displaying excellent stability and reusability of the proposed pH-PPM. This strategy for porous polymer membrane enzyme reactor fabrication has established a platform for enzyme efficiency adjusting. These valve-like distinguished features highlight the outstanding potential of stimuli-responsive enzyme reactor applied for enzyme immobilization and enzyme-related disease treatment.
研究领域:
生物化学
·
材料科学
·
酶工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
·
2015
·Vol. 53
·期 11
·1387-1395
·
IF 3.113
Huan Yu,Jian Sun,Yunti Zhang,Guangyan Zhang,Yanfeng Chu,Renxi Zhuo,Xulin Jiang
A novel kind of graft polymer poly(aspartic acid)-ethanediamine- g -adamantane/methyloxy polyethylene glycol (Pasp-EDA- g -Ad/mPEG) was designed and synthesized for drug delivery in this study. The chemical structure of the prepared polymer was confirmed by proton NMR. The obtained polymer can self-assemble into micelles which were stable under a physiological environment and displayed pH- and β-cyclodextrin (β-CD)-responsive behaviors because of the acid-labile benzoic imine linkage and hydrophobic adamantine groups in the side chains of the polymer. The doxorubicin (Dox)-loaded micelles showed a slow release under physiological conditions and a rapid release after exposure to weakly acidic or β-CD environment. The in vitro cytotoxicity results suggested that the polymer was good at biocompatibility and could remain Dox biologically active. Hence, the Pasp-EDA- g -Ad/mPEG micelles may be applied as promising controlled drug delivery system for hydrophobic antitumor drugs. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53 , 1387–1395
研究领域:
生物材料学
·
药剂学
·
高分子化学
✓ 已验证
产品关联
DOI
高影响因子
Soft Matter
·
2013
·Vol. 9
·期 30
·7267-7273
·
IF 3.909
Xin Gu,Jingjing Wang,Xiaofei Liu,Dongping Zhao,Yinong Wang,Hui Gao,Guolin Wu
To develop poly(amino acid)s with temperature-sensitivity, a series of polyaspartamides with isopropylamide and hydroxyalkylamide pendant groups were synthesized by a successive aminolysis reaction of polysuccinimide. The structure of the resulting polymers was examined by 1H NMR and FT-IR. The polyaspartamide derivatives self-assembled into nanoparticles in water and showed sharp temperature-responsive phase transition behaviour. The phase transition temperature (Tp) could be modulated by the hydrophilic–hydrophobic balance of the copolymer controlled by altering the composition of both pendants. Besides, an antitumor agent, doxorubicin, was successfully loaded into the polymeric nanoparticles via a dialyzing method. The drug release profile was temperature-dependent accelerating significantly above the Tp and decelerating below the Tp. This easily prepared polymeric nanoparticle with excellent biocompatibility and tunable temperature responsiveness has significant potential for controlled drug release applications.
研究领域:
材料科学
·
药学
✓ 已验证
DOI
高影响因子
Arabian Journal of Chemistry
·
2021
·
IF 5.165
Guangyan Zhang,Chenhui Bao,Hui Yi
Previous works reported that some temperature responsive polyaspartamide derivatives exhibited pH responsiveness, although pH responsive functional groups or pH-cleavable linkages were not introduced during the preparing process, which may be related to the hydroxyl groups of their pendant alkanolamide moieties. In order to investigate whether pH will also affect the temperature responsive behavior of temperature responsive polyaspartamide derivatives without hydroxyl groups, four linear alkyl ether-type amine compounds with one ether oxygen atom and 3 to 6 carbon atoms, denoted as OCx (x represents the number of carbon atoms in alkyl ether-type amine compounds), were selected for the aminolysis reaction of poly(succinimide) to design and synthesize the polyaspartamide derivatives bearing alkyl ether pendants, named PASP-OCx. The chemical structures and molecular weights of the obtained polymers were characterized and confirmed by FTIR, 1 H NMR and SEC-MALLS. The water-solubilities, surface tensions and transmittances of PASP-OCx aqueous solutions were also investigated. Results showed that PASP-OCx can be dissolved in deionized water when x is less than or equal to 5. The surface tensions of PASP-OC4 and PASP-OC5 solutions exhibited obvious turning points. Interestingly, transmittances results showed that PASP-OC5 exhibited temperature responsive behaviors under acidic, neutral or alkaline conditions (pH ≤ 10.0); PASP-OC4 only exhibited temperature responsive behaviors under acidic condition (pH ≤ 3.0); while PASP-OC3 did not exhibit temperature responsive behavior. The LCST value of PASP-OC5 and PASP-OC4 can be turned by adjusting the pH value of their solutions, and decreases with decreasing the pH value. Additionally, the influence of pH on the LCST values of PASP-OC4 and PASP-OC5 was investigated by zeta potential, and the results showed that the decrease of LCST values may be due to the reducing of electrostatic repulsion with pH decreasing. Therefore, results showed that pH can also affect the temperature responsive behavior of temperature-responsive polyaspartamide derivatives that do not contain hydroxyl groups.
研究领域:
高分子化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
Gels
·
2025
·Vol. 11
·期 2
·93
·
IF 5.3
Wenzhuo Hou,Hui Yi,Guangyan Zhang
In recent years, hydrogel beads and in situ hydrogels have gained wide attention in various fields such as biomedicine. In this study, 3-(4-hydroxyphenyl) propionic acid (HP) was introduced into the side chain of poly(α,β-[N-(2-hydroxyethyl)-D,L-aspartamide]) (PHEA) to synthesize phenolic hydroxyl-functionalized poly(aspartamide) derivative PHEA-HP with enzyme-catalyzed cross-linking potential. First, the chemical structure of PHEA-HP was characterized by FT-IR, UV and1H NMR, and the results of in vitro cytotoxicity against L929 cell line and hemolysis experiment showed that PHEA-HP did not have toxicity to cells (viability > 90%) and had good blood compatibility. Then, rheological measurement confirmed the formation of PHEA-HP-based in situ hydrogel with a high storage modulus (G′) around 104Pa, and the vial-tilting method revealed that the gelation time of PHEA-HP aqueous solution could be tuned in the wide range of 5–260 s by varying the concentrations of hydrogen peroxide (H2O2) and horseradish peroxidase (HRP). Finally, hydrogel beads of different diameters containing methylene blue (for easy observation) were prepared using a coaxial needle and syringe pumps, and the effect of the flow rate of the outer phase on the diameters of the hydrogel beads was also investigated. Therefore, PHEA-HP may be a promising and safe poly(aspartamide) derivative that can be used to prepare in situ hydrogels and hydrogel beads for applications closely related to the human body.
研究领域:
生物材料学
·
生物医药工程
✓ 已验证
DOI
PubMed
高影响因子
ELECTROPHORESIS
·
2012
·Vol. 34
·期 3
·409-416
·
IF 3.303
Juan Qiao,Li Qi,Huijuan Yan,Yaping Li,Xiaoyu Mu
l -Asparaginase ( l -Asnase) can suppress the growth of malignant cells by rapid depletion of two essential amino acids, l -glutamine ( l -Gln) and l -asparagine ( l -Asn). To study the cytotoxic effect and the secondary complications of l -Asnase in the treatment of acute lymphoblastic leukemia, the development of a novel enzyme reactor of l -Asnase for the hydrolysis of l -Gln, employing the enzyme-gold nanoparticle conjugates in capillary, was reported in this work. First, a microchip CE (MCE)-LIF was established for the separation of l -amino acids ( l -Gln and l -glutamic acid) and studying the hydrolysis of l -Gln by using l -Asnase enzyme reactor. Then, using l -Gln as target analyte, the enzyme kinetics of l -Asnase in free solution, enzyme-gold nanoparticle conjugates (E-GNP), and the enzyme-gold nanoparticle conjugates immobilized in capillary (E-GNP-C) were investigated in detail with the proposed MCE-LIF method. Moreover, for optimizing the enzymatic reaction efficiency, three important parameters, including the length of capillary, the enzyme concentration reacted with gold nanoparticle and the amount of l -Asnase immobilized on the gold nanoparticle, have been studied. Owing to the high specific activity, the E-GNP-C enzyme reactor exhibited the best performance for the hydrolysis of l -Gln.
研究领域:
生物化学
·
医学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2013
·
IF 3.554
Xin Gu,Jingjing Wang,Yanming Wang,Yinong Wang,Hui Gao,Guolin Wu
Biodegradable shell cross-linked nanocapsules were prepared via layer-by-layer assembly of PADH (tertiary amine and hydrazide grafted polyaspartamide) and PACA (carboxyl and aldehyde grafted polyaspartamide) on silica spheres. Both of the polyaspartamide derivatives are water-soluble and biodegradable polymers with a protein-like structure, and obtained by aminolysis reaction of polysuccinimide. The latter is prepared by thermal polycondensation of aspartic acid. Dynamic light scattering and zeta potential measurements were used to analyze the layer-by-layer assembly process. Bovine serum albumin (BSA), as a model protein, was entrapped in the nanocapsules via electrostatic adsorption. Nanocapsules encapsulating BSA were prepared via layer-by-layer assembly on protein-entrapping amino-functionalized silica spheres, hydrazone cross-linking and silica core removal. The BSA release profiles exhibited a pH-dependent behavior. BSA release rate increased significantly as the ambient pH dropped from the physiological pH to acidic. Cell viability study suggests that the obtained polymeric nanocapsules have good biocompatibility. These kinds of novel composite nanocapsules may offer a promising delivery system for proteins.
研究领域:
生物材料
·
药物递送系统
✓ 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）