Journal of biotechnology最新文献_第5页

Antibacterial effects and mechanisms of fisetin-β-cyclodextrin complex under UVA light against Escherichia coli O157:H7 非瑟酮-β-环糊精配合物在UVA光下对大肠杆菌O157:H7的抑菌作用及其机制

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-12-06 DOI: 10.1016/j.jbiotec.2025.12.003

Tao Liu , Yuzhang Zhu , Jiahui Wang , Kun Lin , Xuan Zhang , Huawei Ma , Chaonan Kong , Wei Cai , Lifang Yang , Mingguo Jiang

The development of natural product photosensitizers was a critical cornerstone for applying photodynamic antimicrobial technology in the food industry. The objective of this study was to fabricate complex of fisetin-β-cyclodextrin (FIT-β-CD), explore their photodynamic antimicrobial efficacy and mechanisms, and characterize it through infrared spectroscopy and X-ray diffraction. The results indicatde that this method can produce good dispersibility and water solubility of FIT-β-CD complex.The photodynamic impact of FIT-β-CD was assessed by examining alterations in reactive oxygen species (ROS) production.The results demonstrated that FIT-β-CD can rapidly generate ROS under UVA, with hydrogen peroxide production being 3.73 times higher than in dark conditions. The antimicrobial efficacy of FIT-β-CD against Escherichia coli O157:H7 (E.coli O157:H7) was evaluated based on bactericidal efficacy, cell membrane damage, DNA and protein damage, motility changes, biofilm formation, and extracellular polysaccharide production. In addition, gene expression analysis by RT-qPCR showed its significant inhibition on the two-component system (TCS) and quorum sensing system (QS). The results indicated that FIT-β-CD exhibited efficient, sensitive photodynamic, and antibacterial properties against E.coli O157:H7, making it a novel photosensitizer. These findings imply potential new applications of fisetin in the field of food antimicrobial agents.

天然产物光敏剂的开发是光动力抗菌技术在食品工业中应用的重要基石。本研究的目的是制备非瑟酮-β-环糊精配合物（FIT-β-CD），探讨其光动力抗菌效果和机制，并通过红外光谱和x射线衍射对其进行表征。结果表明，该方法制备的FIT-β-CD配合物具有良好的分散性和水溶性。通过检测活性氧（ROS）产生的变化来评估FIT-β-CD的光动力学影响。结果表明，在UVA条件下，FIT-β-CD可以快速生成ROS，过氧化氢产量是暗条件下的3.73倍。通过对大肠杆菌O157:H7 （E.coli O157:H7）的杀菌效果、细胞膜损伤、DNA和蛋白质损伤、运动改变、生物膜形成和胞外多糖生成等指标评价FIT-β-CD对大肠杆菌O157:H7的抑菌效果。此外，RT-qPCR基因表达分析显示其对双组分系统（TCS）和群体感应系统（QS）有显著抑制作用。结果表明，FIT-β-CD对大肠杆菌O157:H7具有高效、灵敏的光动力学和抗菌性能，是一种新型光敏剂。这些发现暗示了非瑟酮在食品抗菌剂领域的潜在新应用。

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引用次数: 0

Increasing the chiral purity of cellulosic L-lactic acid by D-Lactate oxidase-catalyzed oxidation in engineered lactic acid bacterium Pediococcus acidilactici d -乳酸氧化酶在工程乳酸菌中催化氧化提高纤维素l -乳酸的手性纯度。

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-12-05 DOI: 10.1016/j.jbiotec.2025.12.002

Jiao Liu, Chaolong Qu, Bin Zhang, Jie Bao

Trace amounts of D-lactic acid derived from lignocellulose feedstock and nitrogen additives frequently reduce the chiral purity of L-lactic acid below the polymerization standard during biorefinery fermentations. The spontaneous D-lactic acid degradation catalyzed by the highly substrate specific D-lactate oxidase in lactic acid bacterium provides an ideal solution. This study used a D-lactate oxidase GOX2071 with relatively high activity for construction of D-lactic acid oxidation pathway in the L-lactic acid producing strain Pediococcus acidilactici ZY271. The engineered P. acidilactici LJ2071 strain demonstrated an active D-lactic acid oxidation performance while the high L-lactic acid production property was well maintained. A L-lactic acid chiral purity of 99.63 % was obtained using the D-lactic acid containing wheat straw as feedstock and 40 % of corn steep liquor (CSL) as nitrogen additive to alternate expensive yeast extract. This study provided a practical method for upgrading the chirality of cellulosic L-lactic acid using lignocellulose feedstock and cheap nitrogen additives.

在生物精炼发酵过程中，来自木质纤维素原料和氮添加剂的微量d -乳酸经常使l -乳酸的手性纯度低于聚合标准。乳酸菌中具有高度底物特异性的d -乳酸氧化酶对d -乳酸的自发降解提供了理想的解决方案。本研究利用活性较高的d -乳酸氧化酶GOX2071在产l -乳酸的Pediococcus acidacactii ZY271中构建d -乳酸氧化途径。工程菌株LJ2071在保持高产l -乳酸特性的同时，表现出较强的d -乳酸氧化能力。以小麦秸秆为原料，以40%的玉米浸泡液（CSL）为氮添加剂，替代昂贵的酵母浸膏，得到了手性纯度为99.63%的l -乳酸。本研究为利用木质纤维素原料和廉价的氮添加剂提高纤维素l -乳酸的手性提供了一种实用的方法。

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引用次数: 0

Enhancing heterotrophic lutein production in Chlorella protothecoides through combined phytohormone and nitrogen strategies 植物激素和氮素联合策略促进原小球藻异养叶黄素的产生

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-12-04 DOI: 10.1016/j.jbiotec.2025.12.001

Jiaxin Li , Weiyang Zhao , Yunlei Fu , Ranxuan Li , Jin Liu , Shufang Yang , Jie Zheng , Haijin Mou , Han Sun

Large-scale production of microalgal lutein faces challenges due to limited biomass and lutein content. In this work, we developed an exponential fed-batch model to achieve heterotrophic high-density growth of Chlorella protothecoides CS-41. Then, indole-3-acetic acid (IAA) and high nitrogen were combined to promote lutein accumulation in situ. Fed-batch culture enhanced the TCA cycle of C. protothecoides CS-41 to benefit cell growth while increasing carotenoid flux to facilitate lutein accumulation through redirecting carbon flux towards lutein biosynthesis, improved by IAA. Also, high nitrogen increased lutein content through modulation of CMS (carotenoid methyltransferase synthase), CRTISO (carotenoid isomerase), LCYB (lycopene β-cyclase), ZEP (zeaxanthin epoxidase), and VDE (violaxanthin de-epoxidase). Finally, under heterotrophic conditions, combining 200 mM IAA with 3.6 g/L urea improved pyruvate and 3-phosphoglyceric acid and then boosted lutein content and productivity to 3.27 mg/g and 20.38 mg/L/d, respectively, by increases of 58 % and 56.7 %. Addressing issues including density dilution, container transfer, and in-situ lutein accumulation under heterotrophic high-density conditions offers a cost-effective solution.

由于生物量和叶黄素含量有限，微藻叶黄素的大规模生产面临挑战。本研究建立了小球藻CS-41异养高密度生长的指数补料批量模型。然后，吲哚-3-乙酸（IAA）和高氮配合施用，促进叶黄素原位积累。补料批培养增强了C. protothecoides CS-41的TCA循环，有利于细胞生长，同时增加类胡萝卜素通量，通过将碳通量转向叶黄素的生物合成，促进叶黄素的积累，IAA改善了这一过程。高氮通过调节类胡萝卜素甲基转移酶合成酶（CMS）、类胡萝卜素异构酶（CRTISO）、番茄红素β环化酶（LCYB）、玉米黄质环氧化酶（ZEP）和紫黄质去环氧化酶（VDE）提高叶黄素含量。最后，在异养条件下，200 mM IAA与3.6 g/L尿素配用可改善丙酮酸和3-磷酸甘油酸，叶黄素含量和产量分别提高了3.27 mg/g和20.38 mg/L/d，分别提高了58 %和56.7% %。在异养高密度条件下，解决密度稀释、容器转移和原位叶黄素积累等问题提供了具有成本效益的解决方案。

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引用次数: 0

High specificity of MsmCAR toward 4-hydroxyvaleric acid enables efficient 1,4-pentanediol production from biomass-derived levulinic acid MsmCAR对4-羟戊酸的高特异性使得从生物质衍生的乙酰丙酸中高效生产1,4-戊二醇。

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-12-01 DOI: 10.1016/j.jbiotec.2025.11.020

Suhye Choi , Seung Hun Lee , Yunyeong Kim , Woo Young Jeon , Jung oh Ahn , Shashi Kant Bhatia , Kwon-Young Choi , Jeong Chan Joo , Yung-Hun Yang

Alkanediols are industrial compounds with diverse applications. However, the biological production of C5 diols is limited by the low substrate specificity and efficiency of carboxylic acid reductases (CARs) toward short to medium-chain substrates. We developed a whole-cell biotransformation system for efficient 1,4-pentanediol (1,4-PDO) production, aimed at developing a platform pathway for diol biosynthesis. By screening 10 CARs, we identified MsmCAR from Mycolicibacterium smegmatis MC2 155 as the most effective for C5 diol biosynthesis, with high specificity toward 4-hydroxyvaleric acid (4-HV). We constructed a whole-cell catalyst expressing MsmCAR and enhanced its performance by introducing ppk2b from Corynebacterium glutamicum ATCC 13032 and chnD from Acinetobacter sp., which encode proteins involved in cofactor regeneration. Systematic optimization of the reaction conditions including buffers, cofactors, metal ions, and cultivation parameters led to a maximum titer of 78.10 mM 1,4-PDO, with a productivity of 1.86 mM/h, when using 4-HV as a substrate. To expand the substrate scope to levulinic acid, 3-hydroxybutyrate dehydrogenase and formate dehydrogenase biosynthetic genes were introduced. This system yielded 22.10 mM 1,4-PDO within 10 h. This work highlights the potential of MsmCAR as a versatile biocatalyst and provides a sustainable strategy for producing short- to medium-chain diols from biomass-derived feedstocks.

烷二醇是一种用途广泛的工业化合物。然而，C5二醇的生物生产受到低底物特异性和羧酸还原酶（CARs）对中短链底物的效率的限制。我们开发了一种高效生产1,4-戊二醇（1,4- pdo）的全细胞生物转化系统，旨在开发二醇生物合成的平台途径。通过筛选10个CARs，我们鉴定出来自垢垢分枝杆菌MC2 155的MsmCAR对C5二醇的生物合成最有效，对4-羟基戊酸（4-HV）具有高特异性。我们构建了表达MsmCAR的全细胞催化剂，并通过引入来自谷氨棒状杆菌ATCC 13032的ppk2b和来自不动杆菌sp.的chnD来增强其性能，这两个基因编码参与辅助因子再生的蛋白质。系统优化反应条件，包括缓冲液、辅因子、金属离子和培养参数，以4-HV为底物时，最大滴度为78.10mM 1,4- pdo，产率为1.86mM/h。为了将底物范围扩大到乙酰丙酸，引入了3-羟基丁酸脱氢酶和甲酸脱氢酶生物合成基因。该体系在10h内生成22.10mM的1,4- pdo。这项工作突出了MsmCAR作为一种多功能生物催化剂的潜力，并为从生物质来源的原料中生产短至中链二醇提供了可持续的策略。

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引用次数: 0

Experimental immobilization of Clostridium histolyticum collagenases on green-synthesized CuO nanoparticles supported by bioinformatics analysis 绿色合成氧化铜纳米颗粒固定化溶组织梭菌胶原酶的实验研究。

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-11-29 DOI: 10.1016/j.jbiotec.2025.11.019

Farzaneh Barati , Fakhrisadat Hosseini , Parinaz Ghadam , Seyed Shahriar Arab

Enzymes are widely used in various industries due to their eco-friendly nature, high selectivity, and ability to operate under mild conditions. However, large-scale applications are often hindered by challenges such as limited stability, high costs, and difficulties in recyclability. Enzyme immobilization presents a promising strategy to overcome these limitations. Microbial collagenases, particularly those from Clostridium histolyticum, play a crucial role in industrial and biomedical applications. In silico analyses effectively predict enzyme immobilization outcomes, minimizing experimental time and cost. This study employed enzyme surface analysis, a bioinformatics approach, to determine the surface charge type of the support for the physical immobilization of C. histolyticum collagenases. The analysis identified the most suitable regions on the enzyme surfaces for attachment—positively charged and distant from critical sites—ensuring minimal disruption to activity. Copper oxide (CuO) nanoparticles (NPs) were synthesized using walnut green husk extract and subsequently characterized. The green-synthesized CuO NPs were monodisperse and spherical (∼40 nm) with a negatively charged surface, confirming their suitability as supports for enzyme immobilization. Employing the CuO NPs as supports resulted in an immobilization yield of 42.15 % and an activity yield of 146.2 %. Further optimization of immobilization conditions could improve IY. The high AY suggests that immobilization did not hinder enzyme function but may have enhanced enzyme-substrate affinity and increased local substrate concentration, thereby boosting enzyme efficiency.

酶因其生态友好、高选择性和在温和条件下工作的能力而广泛应用于各个行业。然而，大规模应用经常受到诸如稳定性有限、成本高和可回收性困难等挑战的阻碍。酶固定化是克服这些限制的一种很有前途的策略。微生物胶原酶，特别是来自溶组织梭菌的胶原酶，在工业和生物医学应用中起着至关重要的作用。在硅分析有效地预测酶固定结果，最大限度地减少实验时间和成本。本研究采用酶表面分析这一生物信息学方法，确定了溶组织菌胶原酶物理固定载体的表面电荷类型。分析确定了酶表面最适合附着的区域-带正电且远离关键位点-确保对活性的干扰最小。以核桃绿壳提取物为原料合成了氧化铜纳米颗粒，并对其进行了表征。绿色合成的CuO NPs为单分散球形（~40nm），表面带负电荷，证实了其作为固定化酶载体的适宜性。采用CuO NPs作为载体，固定化产率为42.15%，活性产率为146.2%。进一步优化固定条件可以提高IY。高AY表明固定化不会阻碍酶的功能，但可能增强了酶与底物的亲和力，增加了局部底物浓度，从而提高了酶的效率。

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引用次数: 0

Directional lactic acid production could mitigate antibiotic and ARGs pollution 定向乳酸生产可以减轻抗生素和ARGs的污染

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-11-27 DOI: 10.1016/j.jbiotec.2025.11.014

Fubin Yin , Tianjing Lian , Haoying Qu , Dongan Cui , Xiaomeng Li , Yangyang Cai , Hongmin Dong

The technology of directional lactic acid production (DLAP) for animal manure is an innovative way of value-added utilization, but the influence of residual antibiotics in animal manure on the DLAP is still unclear, especially the degradation rate and degradation pathways of antibiotic with residues lactic acid bacteria (LAB). In this study, the most common residual antibiotic (Sulfachloropyridazine, SCP) and LAB (Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus plantarum and Lactobacillus casei) were employed as the research objects, the SCP degradation, degradation pathways and antibiotic resistance genes (ARGs) with different LAB were investigated in pure culture. Results showed that LAB has a positive effect on the reduction in ARGs (sul1, sul2, sul3, sulA, intI1 and tnp A). The SCP degradation rates were 90.3 %, 85.1 %, 86.1 % and 84.0 % with the growth of Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus plantarum and Lactobacillus casei at 50 mg/L, respectively. And the SCP degradation pathway is different for LAB, but the main decomposition functions, including S-N bond cleavage, CH₃ release, SO₂ release, nitration, hydroxylation, NH₂ release and C-N bond cleavage, are similar. And most of intermediate products of SCP were lower toxicity compared to the parent compound. The findings proved the DLAP process as a guidance for a potential solution for reducing antibiotic and ARGs contamination.

畜禽粪便定向产乳酸（DLAP）技术是一种创新的增值利用方式，但畜禽粪便中残留抗生素对DLAP的影响尚不清楚，尤其是抗生素与残留乳酸菌（LAB）的降解速率和降解途径。本研究以最常见的残留抗生素磺胺氯吡嗪（磺胺氯吡嗪）和乳酸菌（保加利亚乳杆菌、嗜酸乳杆菌、植物乳杆菌和干酪乳杆菌）为研究对象，在纯培养中研究了不同乳酸菌对SCP的降解、降解途径和抗生素抗性基因（ARGs）。结果表明，LAB对ARGs （sul1、sul2、sul3、sulA、intI1和tnp a）的减少具有积极作用。当保加利亚乳杆菌、嗜酸乳杆菌、植物乳杆菌和干酪乳杆菌生长在50 mg/L时，SCP的降解率分别为90.3 %、85.1 %、86.1 %和84.0 %。LAB的SCP降解途径不同，但主要分解功能相似，包括S-N键裂解、CH3释放、SO2释放、硝化、羟基化、NH2释放和C-N键裂解。与母体化合物相比，SCP的大部分中间产物毒性较低。研究结果证明，DLAP工艺为减少抗生素和ARGs污染的潜在解决方案提供了指导。

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引用次数: 0

Sodium alginate-immobilized epoxide hydrolase: A multifaceted strategy for enhanced stability, reusability, and catalytic performance 海藻酸钠固定化环氧化物水解酶：提高稳定性、可重用性和催化性能的多方面策略

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-11-27 DOI: 10.1016/j.jbiotec.2025.11.017

Zongzhong Yu , Meinan Zhu , Xiao Gu , Zhongkun Wu , Peiqin Chen , Chunying Jin , Junning Zhao , Guangya Zhang , Wei Jiang

Immobilized macromolecular enzymes effectively address critical challenges including environmental sensitivity, thermal instability, and non-reusability, thereby establishing the fundamental and practical significance of enzyme immobilization research. This study employed sodium alginate (SA), ZIF-8, and Bi-EA materials to immobilize Aspergillus carlsbadensis-derived epoxide hydrolase (AcEH). Comparative analysis revealed SA's superior immobilization efficiency. Material characterization via SEM, FTIR, and XRD was performed, followed by optimization of SA immobilization parameters. The immobilized enzyme maintained activity over 6 reuse cycles. Incorporating 0.5 wt% carboxymethyl cellulose (CMC) extended AcEH@SA-CMC reusability to 8 cycles. Magnetic modification through Fe₃O₄ powder incorporation yielded AcEH@SA-CMC- Fe₃O₄ hydrogel with enhanced recoverability. Results demonstrate SA's exceptional biocompatibility underpins its immobilization efficacy, while CMC co-entanglement creates a porous network facilitating mass transfer and mechanical reinforcement. Fe₃O₄ powder plays a promoting role in improving enzyme activity. This methodology not only evaluates immobilization matrices but establishes an optimized protocol for macromolecular AcEH immobilization.

固定化大分子酶有效地解决了环境敏感性、热不稳定性和不可重复使用等关键挑战，从而确立了酶固定化研究的基础和现实意义。本研究采用海藻酸钠（SA）、ZIF-8和Bi-EA材料固定化卡尔斯巴登曲霉衍生环氧化物水解酶（AcEH）。对比分析表明，SA具有较好的固定化效果。通过SEM， FTIR和XRD对材料进行了表征，并对SA的固定参数进行了优化。固定化酶在6次重复使用循环中保持活性。加入0.5 wt%羧甲基纤维素（CMC）将AcEH@SA-CMC可重复使用延长至8次循环。通过掺入Fe3O4粉末进行磁改性，得到了回收率提高的AcEH@SA-CMC- Fe3O4水凝胶。结果表明，SA的特殊生物相容性支撑了其固定效果，而CMC的共缠结形成了多孔网络，促进了传质和机械加固。Fe3O4粉末对提高酶活性有促进作用。该方法不仅评价了固定基质，而且建立了大分子AcEH固定的优化方案。

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引用次数: 0

Human beta-defensin 3-functionalized Fe/GMP nanozyme for multifunctional antimicrobial and anticancer activity against Helicobacter pylori-associated gastrointestinal cancer 人β -防御素3功能化铁/GMP纳米酶对幽门螺杆菌相关胃肠道肿瘤的多功能抗菌和抗癌活性

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-11-26 DOI: 10.1016/j.jbiotec.2025.11.018

Yoganathan Kamaraj , Veenayohini Kumaresan , Jinhao Hu , Daochen Zhu

Background

The rising incidence of Helicobacter pylori-associated infections and colorectal cancer necessitates multifunctional therapeutics targeting both microbial and tumor pathologies. However, antimicrobial peptides (AMPs) like human β-defensin 3 (hBD-3) faces challenges such as proteolytic degradation and poor bioavailability. To address these limitations, we developed a novel hybrid nanozyme by immobilizing hBD-3 onto a guanosine monophosphate-coordinated iron framework (Fe/GMP), known for its biocompatibility and intrinsic peroxidase-like activity.

Methods

The hBD-3@Fe/GMP nanozyme was synthesized and characterized for its physicochemical and catalytic properties. Its antibacterial activity against H. pylori was assessed via agar diffusion, biofilm inhibition, and virulence gene expression. Anti-colon cancer potential was evaluated in HT-29 cells using assays for cytotoxicity, ROS generation, apoptosis, migration inhibition, and redox biomarkers. in vivo antitumor efficacy was studied using a colon carcinoma xenograft mice model.

Results

hBD-3@Fe/GMP showed enhanced peroxidase-like activity with elevated ROS production than Fe/GMP alone. It significantly inhibited H. pylori growth, biofilm formation, and virulence gene expression (babA, alpA, alpB, flaA, flaB). In HT-29 cells, it induced cytotoxicity, suppressed antioxidant enzymes, and triggered apoptosis via p53 and Bax upregulation and Bcl-2 downregulation. In tumor xenograft model, it reduced tumor volume and weight.

Conclusion

This study reports, for the first time, a hybrid nanozyme that synergistically integrates the antimicrobial potency of hBD-3 with the catalytic redox functionality of Fe/GMP, offering dual action against H. pylori infection and colorectal cancer. The multifunctional therapeutic potential and biocompatibility of hBD-3@Fe/GMP mark a novel paradigm in the development of next-generation nanozymes for combinatorial infectious and oncological interventions.

背景：幽门螺杆菌相关感染和结直肠癌的发病率不断上升，需要针对微生物和肿瘤病理的多功能治疗。然而，抗菌肽（AMPs）如人β-防御素3 （hBD-3）面临着蛋白水解降解和生物利用度差等挑战。为了解决这些限制，我们通过将hBD-3固定在鸟苷单磷酸配位铁框架（Fe/GMP）上开发了一种新型杂交纳米酶，该框架以其生物相容性和内在过氧化物酶样活性而闻名。方法合成hBD-3@Fe/GMP纳米酶，并对其理化性质和催化性能进行表征。通过琼脂扩散、生物膜抑制和毒力基因表达评价其对幽门螺杆菌的抑菌活性。通过细胞毒性、ROS生成、凋亡、迁移抑制和氧化还原生物标志物的测定来评估HT-29细胞的抗结肠癌潜力。采用结肠癌异种移植小鼠模型研究其体内抗肿瘤效果。ResultshBD-3@Fe/GMP显示，与单独Fe/GMP相比，过氧化物酶样活性增强，ROS生成增加。显著抑制幽门螺杆菌生长、生物膜形成和毒力基因（babA、alpA、alpB、flaA、flaB）表达。在HT-29细胞中，它通过上调p53和Bax，下调Bcl-2，诱导细胞毒性，抑制抗氧化酶，引发细胞凋亡。在异种肿瘤移植模型中，它能减小肿瘤体积和重量。结论本研究首次报道了一种将hBD-3的抗菌效力与Fe/GMP的催化氧化还原功能协同结合的杂交纳米酶，具有抗幽门螺杆菌感染和结直肠癌的双重作用。hBD-3@Fe/GMP的多功能治疗潜力和生物相容性标志着用于联合感染和肿瘤干预的下一代纳米酶的开发的新范式。

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引用次数: 0

Emerging strategies for enhanced glutathione biosynthesis and its biomedical applications 加强谷胱甘肽生物合成及其生物医学应用的新策略

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-11-25 DOI: 10.1016/j.jbiotec.2025.11.016

Yajie Wang , Ruixue Ma , Jia Zhou , Zhongbiao Tan , Hongliang Li , Hao Shi , Yegui Zhang

Glutathione (GSH), a ubiquitous bioactive tripeptide, plays a central role in antioxidant defense, detoxification, and cellular metabolism. This review highlights advanced strategies to enhance GSH production, emphasizing strain improvement via traditional mutagenesis and genetic engineering. Optimization of microbial fermentation through carbon source selection, amino acid precursors, and ATP regeneration combined with metabolic engineering approaches, has significantly improved GSH yields in Saccharomyces cerevisiae and Escherichia coli. Clinically, GSH is used in managing liver diseases, oxidative stress, and immune dysfunction. Emerging applications, particularly in oncology, show promise. This review also compares production methods such as chemical synthesis, enzymatic catalysis, and microbial fermentation, highlighting microbial fermentation for its sustainability, cost-efficiency, and scalability. Future research should focus on refining detection methods, elucidating GSH’s therapeutic mechanisms, and broadening its applications across pharmaceuticals, nutrition, and cosmetics.

谷胱甘肽（GSH）是一种普遍存在的生物活性三肽，在抗氧化防御、解毒和细胞代谢中起着核心作用。本文综述了提高谷胱甘肽产量的先进策略，强调了通过传统的诱变和基因工程对菌株进行改良。通过碳源选择、氨基酸前体和ATP再生结合代谢工程方法优化微生物发酵，显著提高了酿酒酵母和大肠杆菌的谷胱甘肽产量。在临床上，谷胱甘肽被用于治疗肝脏疾病、氧化应激和免疫功能障碍。新兴的应用，特别是在肿瘤学领域，显示出了希望。本文还比较了化学合成、酶催化和微生物发酵等生产方法，重点介绍了微生物发酵的可持续性、成本效益和可扩展性。未来的研究应集中于改进检测方法，阐明谷胱甘肽的治疗机制，并扩大其在制药、营养和化妆品领域的应用。

{"title":"Emerging strategies for enhanced glutathione biosynthesis and its biomedical applications","authors":"Yajie Wang , Ruixue Ma , Jia Zhou , Zhongbiao Tan , Hongliang Li , Hao Shi , Yegui Zhang","doi":"10.1016/j.jbiotec.2025.11.016","DOIUrl":"10.1016/j.jbiotec.2025.11.016","url":null,"abstract":"<div><div>Glutathione (GSH), a ubiquitous bioactive tripeptide, plays a central role in antioxidant defense, detoxification, and cellular metabolism. This review highlights advanced strategies to enhance GSH production, emphasizing strain improvement via traditional mutagenesis and genetic engineering. Optimization of microbial fermentation through carbon source selection, amino acid precursors, and ATP regeneration combined with metabolic engineering approaches, has significantly improved GSH yields in <em>Saccharomyces cerevisiae</em> and <em>Escherichia coli</em>. Clinically, GSH is used in managing liver diseases, oxidative stress, and immune dysfunction. Emerging applications, particularly in oncology, show promise. This review also compares production methods such as chemical synthesis, enzymatic catalysis, and microbial fermentation, highlighting microbial fermentation for its sustainability, cost-efficiency, and scalability. Future research should focus on refining detection methods, elucidating GSH’s therapeutic mechanisms, and broadening its applications across pharmaceuticals, nutrition, and cosmetics.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"410 ","pages":"Pages 45-56"},"PeriodicalIF":3.9,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145622161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Methanol-induced metabolic disturbances in protein expression in Pichia pastoris: A review of the interaction between amino acid synthesis and higher alcohol pathways 毕赤酵母中甲醇诱导的蛋白质表达代谢紊乱：氨基酸合成与高级酒精途径相互作用的综述

IF 3.9 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of biotechnology

Pub Date : 2025-11-25 DOI: 10.1016/j.jbiotec.2025.11.015

Lifen He , Danling Tang , Fan Feng , Tao Hong , Mingjing Zheng , Xiping Du , Yanbing Zhu , Yuanfan Yang , Zedong Jiang , Fan He , Lijun Li , Zhipeng Li , Hui Ni , Qingbiao Li

Pichia pastoris is a prominent host for recombinant protein production, utilizing the methanol-inducible Alcohol Oxidase 1 (AOX1) promoter to express thousands of heterologous proteins. However, methanol induction, while driving high-level protein expression, simultaneously imposes a pronounced metabolic burden. This review highlights that a balanced and ample supply of amino acids is indispensable for efficient protein synthesis. The induction process leads to the accumulation of by-products, notably higher alcohols, which can negatively impact protein quality. The dynamic interplay between these two pathways is not fully understood. In addition, the lack of quantitative models for their competition over shared precursors hinders rational metabolic engineering and impedes the industrial exploitation of P. pastoris. Therefore, this review systematically dissects the link between methanol induction, amino acid metabolism, and higher alcohol synthesis. It specifically examines how methanol-triggered perturbations in amino acid metabolism propagate to modulate higher alcohol formation. Special attention is given to key metabolic nodes, such as pyruvate and α-ketoisovalerate, where carbon flux diverges between biosynthesis and by-product formation. This review provides significant implications for a deeper understanding of the metabolic processes in P. pastoris, offering comprehensive mechanistic insights and guidance for optimizing yeast fermentation and enhancing recombinant protein production.

毕赤酵母是重组蛋白生产的重要宿主，利用甲醇诱导的乙醇氧化酶1 （AOX1）启动子表达数千种异源蛋白。然而，甲醇诱导在驱动高水平蛋白表达的同时，也会带来明显的代谢负担。这篇综述强调了平衡和充足的氨基酸供应对于有效的蛋白质合成是必不可少的。诱导过程导致副产物的积累，特别是高醇，这可能对蛋白质质量产生负面影响。这两种途径之间的动态相互作用尚不完全清楚。此外，缺乏对共享前体竞争的定量模型，阻碍了合理的代谢工程，阻碍了巴氏酵母的工业开发。因此，本文系统地剖析了甲醇诱导、氨基酸代谢和高级醇合成之间的联系。它特别研究了甲醇触发的氨基酸代谢扰动如何传播以调节更高的酒精形成。特别关注关键的代谢节点，如丙酮酸和α-酮异戊酸，其中碳通量在生物合成和副产物形成之间偏离。这一综述为深入了解酵母的代谢过程提供了重要的意义，为优化酵母发酵和提高重组蛋白的生产提供了全面的机制见解和指导。

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引用次数: 0