RSC Advances
·
2023
·Vol. 13
·期 27
·18651-18657
·
IF 3.9
Jie Yu,Danwei Cen,Yongcheng Chen,Hailan Zhao,Mengyue Xu,Sulan Wu,Shuo Wang,Qiao Jin,Ting Shen
Antibiotic resistance is a big threat to public health. How to improve the therapeutic efficacy of conventional antibiotics is an effective way to address this issue. In order to enhance the antibacterial activity of conventional antibiotic erythromycin (EM), EM is conjugated to positively charged ε-poly-L-lysine (EPL) to obtain EPL modified EM (EPL-EM). The grafting ratio of EM can be calculated from the 1H NMR spectrum. EPL-EM is stable in physiological environment, while EM can be readily released from EPL-EM upon incubating with esterase which can be secreted by most bacteria. Because of the presence of cationic EPL, EPL-EM showed much stronger antibacterial activity than free EM, with much lower minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Moreover, compared to free EM, the development of drug resistance can be slowed down if EPL-EM is used, which can be ascribed to the reduction of EM dosage. Meanwhile, EPL-EM cannot induce hemolysis and cytotoxicity, which indicates that EPL-EM exhibits excellent biocompatibility. The design of EPL-EM with enhanced antibacterial activity and excellent biocompatibility provides an innovative way to combat antibiotic resistance.
研究领域:
药理学
·
微生物学
·
治疗学
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DOI
PubMed
高影响因子
BIOTECHNOLOGY AND BIOPROCESS ENGINEERING
·
2015
·Vol. 19
·期 6
·965-972
·
IF 1.113
Li Naiqiang,Chou Howard,Yu Lijun,Xu Yan
Cadaverine, as a biogenic amine, is an important platform chemical for the production of industrial polymers, such as polyamides, polyurethanes, and nylon. Previous efforts focused on the bio-based production of cadaverine using two lysine decarboxylases of Escherichia coli CadA and LdcC. In this study, we report the biotransformation of cadaverine using a lysine decarboxylase from Klebsiella oxytoca . Codon optimization of the gene encoding this enzyme was carried on for the heterologous expression in E. coli , which led to a system that converted more than 24% lysine-HCl to cadaverine compared to the same system expressing CadA. The system was further optimized by using three different inducible promoters to control the expression of lysine decarboxylase gene of K. oxytoca in E. coli . The final optimized system converted lysine-HCl to cadaverine at a conversion rate of 0.133%/min/g. When the optimized system described above is coupled to an industrial process, the combined process has the potential to produce cadaverine with high conversion efficiency (46%) from sugar.
研究领域:
生物化学
·
合成生物学
·
工业微生物学
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DOI
高影响因子
ChemCatChem
·
2021
·Vol. 13
·期 23
·5047-5055
·
IF 5.686
Cong Gao,Jiaping Wang,Liang Guo,Guipeng Hu,Jia Liu,Wei Song,Liming Liu,Xiulai Chen
Graphical Biocatalysis : In this study, an efficient synthetic microbial consortium for glutaric acid production was developed by dividing the cadaverine pathway into two engineered strains. Moreover, strategies of cofactor regeneration and colloidal chitin based-immobilization were implemented to provide a low-cost approach for glutaric acid biosynthesis under mild reaction conditions. Glutaric acid is an important C5 platform compound for the synthesis of nylon polymers. However, its production titer and cost are limited by the need for expensive cofactors addition as well as the difficulty of reusing microbial catalysts. Herein, to address these problems, two regeneration systems each for NAD(P) + and α-ketoglutaric acid were introduced into a five-enzyme cadaverine pathway for a whole-cell biocatalytic approach. We demonstrated the efficient conversion of lysine to glutaric acid in a synthetic microbial consortium manner, producing 73.2 g/L glutaric acid with a 74 % molar yield in a 5-L bioreactor scale. Moreover, with a colloidal chitin-based immobilization, the engineered microbial consortium exhibited good stability and reusability in a five-cycle bioconversion. This study provides an efficient microbial platform for glutaric acid production by developing a cheaper and universal cell immobilization approach.
研究领域:
生物技术
·
生物化工
·
代谢工程
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DOI
高影响因子
MATERIALS CHEMISTRY AND PHYSICS
·
2026
·
IF 4.7
Sheng Lin,Yuting Wang,Chunxiang Huang,Yu Niu,Yongming Liu,Wangchuan Xiao,Fenghua Chen,Rongrong Xue
Co-amorphous systems, including co-amorphous and co-amorphous salts, can enhance the solubility of poorly water-soluble small molecules. It is important to identify them because co-amorphous and co-amorphous salts have different physicochemical properties. Co-amorphous system of luteolin (LUT, a well-known poorly soluble flavonoid) and amino acids at a molar ratio of 1:1 was prepared using neat ball milling. Only amorphous luteolin-arginine (LUT-Arg) and luteolin-lysine (LUT-Lys) exhibit significant solubility enhancements in the media of water and PBS. The Δ p K a rule suggests that LUT-Arg (Δ p K a , 2.8) and LUT-Lys (Δ p K a , 2.9) are close to co-amorphous salts. Diffuse reflectance spectroscopy and Raman spectroscopy confirmed that LUT-Arg and LUT-Lys are co-amorphous salts, while IR spectroscopy, the most common used method, cannot distinguish them. Comprehensive multiple characterizations (>2) are essential to confirm the formation of co-amorphous or co-amorphous salts, such as applying the Δ p K a rule, diffuse reflectance spectroscopy, and Raman spectroscopy for LUT-Arg and LUT-Lys.
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DOI
高影响因子
JOURNAL OF PROTEOME RESEARCH
·
2024
·
IF 3.8
Huanying Pang,Weijie Zhang,Xuelian Lin,Fuyuan Zeng,Xing Xiao,Zhiqing Wei,Shi Wang,Jichang Jian,Na Wang,Wanxin Li
Protein succinylation modification is a common post-translational modification (PTM) that plays an important role in bacterial metabolic regulation. In this study, quantitative analysis was conducted on the succinylated proteome of wild-type and florfenicol-resistant Vibrio alginolyticus to investigate the mechanism of succinylation regulating antibiotic resistance. Bioinformatic analysis showed that the differentially succinylated proteins were mainly enriched in energy metabolism, and it was found that the succinylation level of phosphoenolpyruvate carboxyl kinase (PEPCK) was highly expressed in the florfenicol-resistant strain. Site-directed mutagenesis was used to mutate the lysine (K) at the succinylation site of PEPCK to glutamic acid (E) and arginine (R), respectively, to investigate the function of lysine succinylation of PEPCK in the florfenicol resistance of V. alginolyticus. The detection of site-directed mutagenesis strain viability under florfenicol revealed that the survival rate of the E mutant was significantly higher than that of the R mutant and wild type, indicating that succinylation modification of PEPCK protein may affect the resistance of V. alginolyticus to florfenicol. This study indicates the important role of PEPCK during V. alginolyticus antibiotic-resistance evolution and provides a theoretical basis for the prevention and control of vibriosis and the development of new antibiotics.
研究领域:
微生物学
·
分子生物学
·
药理学
·
蛋白质组学
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DOI
PubMed
高影响因子
Polymer Chemistry
·
2019
·Vol. 10
·期 47
·6432-6439
·
IF 4.76
Luqi Zhu,Yan Xiao,Jiaxiao Zhang,Siqi Zheng,Meidong Lang
Polypeptides serve as a bridge between natural macromolecules and synthetic polymers, leading to the development of biocompatible and biodegradable materials with diverse and complex structures. Here, nucleobase modified polylysine (PLL-co-PTLL) was synthesized via post-polymerization modification of polylysine with thymine (T). Then, melamine (M) with three thymine-like faces was taken as a molecular chaperone analogue to drive the self-assembly of PLL-co-PTLL. It was observed that 7M–1T (M : T = 7 : 1) was the appropriate molar ratio for the pronounced self-assembly, resulting in regular and uniform fibers with an extremely high aspect ratio when the substitution degree of T was relatively low (around 27%). Furthermore, the morphological transformation from fibrous to spherical could be achieved by simply increasing the substitution degree of T. We proposed that melamine and thymine could assemble into a tetrameric structure, which enabled the accumulation of polypeptide chains in a cooperative nucleation-growth polymerization mechanism. Therefore, multiple H-bonding faces created between designable substitution polypeptides and complementary molecules would promote synergistic and hierarchical self-assembly processes.
研究领域:
生物化学
·
材料科学
·
分子生物学
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产品关联
DOI
高影响因子
BIOPOLYMERS
·
2017
·Vol. 107
·期 11
·e23041
·
IF 1.908
Xiaokai Su,Xinyu Zhou,Zhengzhong Tan,Chuncai Zhou
A series of amphiphilic diblock copolypeptides (K 30 - b -F 15 , K 30 - b -F 30 , and K 30 - b -F 45 ) were synthesized via N -carboxy-α-amino-anhydride ring-opening polymerization. The copolypeptides had excellent antibacterial efficacy to both Gram positive ( S. aureus ) and Gram negative ( E. coli ) bacteria. The minimum inhibitory concentrations (MICs) against E. coli and S. aureus are 8 μg mL −1 and 2 μg mL −1 , respectively, lower than most natural and artificial antimicrobial peptides (AMPs). The morphological changes of the bacteria treated with diblock copolypeptides were investigated by transmission electron microscopy; the results proved that the diblock copolypeptides had a similar antibacterial pore-forming mechanism to natural cationic peptides. This was confirmed by laser scanning confocal microscope images. CCK-8 results and the MICs showed that the diblock copolypeptides have high selectivity to bacteria, which suggested that the diblock copolypeptides could be excellent candidates to replace traditional antibiotics in future. Graphical
研究领域:
生物材料学
·
微生物学
·
聚合物化学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Polymer Materials
·
2022
·
IF 4.855
Hui Liu,Miaomiao Han,Xiao Liu,Shengxiang Ji
AMP-mimicking polymers have the potential to serve as an alternative to small-molecule antifungal drugs. Herein, we synthesized four different molecular weight poly(α-lysine) (α-PLn, n = 1–4) and further modified α-PLn to afford guanylated α-PLn (α-PLn-Gx, where x denotes the percentage of guanylation) with enhanced antifungal activities. α-PLn exhibited good antibacterial activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), with minimal inhibitory concentration (MIC) values of 24–96 μg/mL, but it did not show antifungal activities against Candida albicans, Candida parapsilosis, Candida krusei, and Candida glabrata, except for Candida tropicalis (MIC < 3 μg/mL). After guanylation, the antifungal activities of α-PLn-Gx against C. albicans, C. krusei, and C. parapsilosis were significantly improved when x ≥ 80 and the MIC values of α-PL3-G100 were reduced by >32-fold, 64-fold, and >16-fold, respectively, compared to that of the corresponding α-PL3. The mechanistic studies demonstrated that α-PL3-G100 disrupted the integrity of cell membranes of C. albicans.
研究领域:
微生物学
·
药物化学
·
生物材料
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产品关联
DOI
高影响因子
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS
·
2025
·Vol. 113
·期 1
·e35528
·
IF 3.4
Yifan Lu,Xiangxin Lou,Wenxin Wang,Ziting Yang,Haochen Yao,Jinglei Wu
Massive bleeding and bacterial infection of wounds may be life-threatening or even lead to death. Nowadays, gelatin-based hemostatic sponges have been widely used, but gelatin is not antibacterial and has poor structural stability. In this study, we mixed an antibacterial polypeptide, ε-poly-L-lysine (EPL), into gelatin. A gelatin/ε-poly-L-lysine (Gel/EPL) sponge with hemostatic and antibacterial functions was prepared by ultraviolet (UV) crosslinking lyophilized Gel/EPL composite. Scanning electron microscopy showed that the sponge had an interconnected porous structure. The incorporation of EPL increased the hydrophilicity and water absorption capacity of the Gel/EPL sponge. The sponge had better structural stability after UV crosslinking. The antibacterial assay showed that bacteria could not grow normally around the Gel/EPL sponge. The contact between blood components and the sponge initiated coagulation via exogenous pathway activation, and no hemolysis occurred. In addition, in vivo experiments confirmed that the sponge has a faster clotting time and lower blood loss. These findings show that the developed Gel/EPL sponge has great potential as a novel hemostatic agent that can quickly stop bleeding and fight bacterial infections.
研究领域:
生物材料学
·
医学工程
·
药剂学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF SOL-GEL SCIENCE AND TECHNOLOGY
·
2019
·Vol. 92
·期 1
·134-145
·
IF 1.986
Xia Lijian,Yao Binbin,Shi Hao,Shi Zhekun,Wang Wenpin,Kan Ze
In this paper, we report the fundamental method for controlling monodispersed silica nanoparticles size ranged from 10 to ~135 nm assisted by lysine or lysine hydrochloride, during which the seed regrowth technique was utilized. The synthesis was prepared in the water-base system, which was environment friendly and convenient. According to our research, the influence factors of co-solvent system, molar content of additional TEOS, and molar ratio composition of additional TEOS/seeds were confirmed. The final morphology and size of silica nanoparticles can be tuned by changing the amount of additional TEOS and the seeds size. To guarantee the monodispersity of final particles. In the regrowth process, cyclohexane used as the co-solvent floated on the surface of water to block additional TEOS contact with water directly, and made the silicate intermedium consumable for the growth of the parent particles immediately, while not forming new nucleation. In such a condition, to lower the cost and prepare mass production, the lysine was replaced by lysine hydrochloride, meanwhile, triethylamine was introduced to neutralize the hydrochloride. It should be noted that as the particle size increased to be more than 100 nm, when usinglysine hydrochloride and triethylamine, the types of nitrogen adsorption–desorption isotherms changed from H1 to H3; in contrast, the isotherms of the particles were changed from H2 to H1 when catalyzed by lysine.
研究领域:
材料科学
·
纳米技术
·
化学
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产品关联
DOI
高影响因子
CHINESE JOURNAL OF POLYMER SCIENCE
·
2022
·Vol. 41
·期 3
·345-355
·
IF 3.815
Liu Hui,Liu Xiao,Cao Yuan-Qiao,Liu Ming,Han Miao-Miao,Ji Sheng-Xiang
Antimicrobial peptides (AMPs) have been considered as an alternative to small molecule antibiotics since they are difficult to develop antimicrobial resistance. Hyperbranched polylysine (HPL), an AMP mimics, has gained attention due to its broad-spectrum antibacterial activities, but it also suffers from high toxicity. Here we report a facile strategy to engineer the toxicity of HPL by copolymerizing lysine (K) with a hydrophobic amino acid, e.g. , alanine (A), tryptophan (W) or phenylalanine (F), to afford hyperbranched random copolymers. These copolymers have comparable antibacterial activities to HPL while their cytotoxicities and in vivo toxicities are lowered when the type and content of hydrophobic amino acid and the size of copolymers are optimized. The G. mellonella infection model demonstrates that the copolymers are effective against the S. aureus infection in vivo . The copolymers kill the bacteria through the disruption of cell membranes and the bacteria do not develop resistance to the copolymers.
研究领域:
材料科学
·
生物医学工程
·
微生物学
·
药学
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产品关联
DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-19
·
IF 16.6
Li Yatian,Gao Zhenyue,Wang Yuhong,Pang Bo,Zhang Binbin,Hu Ruxin,Wang Yuqing,Liu Chao,Zhang Xuebin,Yang Jingxuan,Mei Mei,Wang Yongzhi,Zhou Xuan,Li Min,Ren Yu
Temozolomide (TMZ) therapy offers minimal clinical benefits in patients with glioblastoma multiforme (GBM) with high EGFR activity, underscoring the need for effective combination therapy. Here, we show that tonicity-responsive enhancer binding protein (NFAT5) lysine methylation, is a determinant of TMZ response. Mechanistically, EGFR activation induces phosphorylated EZH2 (Ser21) binding and triggers NFAT5 methylation at K668. Methylation prevents NFAT5 cytoplasm interaction with E3 ligase TRAF6, thus blocks NFAT5 lysosomal degradation and cytosol localization restriction, which was mediated by TRAF6 induced K63-linked ubiquitination, resulting in NFAT5 protein stabilization, nuclear accumulation and activation. Methylated NFAT5 leads to the upregulation of MGMT, a transcriptional target of NFAT5, which is responsible for unfavorable TMZ response. Inhibition of NFAT5 K668 methylation improved TMZ efficacy in orthotopic xenografts and patient-derived xenografts (PDX) models. Notably, NFAT5 K668 methylation levels are elevated in TMZ-refractory specimens and confer poor prognosis. Our findings suggest targeting NFAT5 methylation is a promising therapeutic strategy to improve TMZ response in tumors with EGFR activation.
研究领域:
肿瘤学
·
分子生物学
·
癌症治疗
·
神经肿瘤学
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产品关联
DOI
PubMed
高影响因子
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