Biotechnology Letters最新文献

High-density heterotrophic cultivation of a cell-wall-deficient Chlamydomonas reinhardtii strain by fed-batch strategy. 一株细胞壁缺陷莱茵衣藻高密度异养培养的补料分批策略。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-07-03 DOI: 10.1007/s10529-025-03614-3

Kaidi Zhou, Tao Yu, Minxi Wan, Zhengxu Bao, Wenming Bai, Weiliang Wang, Yuanguang Li

{"title":"High-density heterotrophic cultivation of a cell-wall-deficient Chlamydomonas reinhardtii strain by fed-batch strategy.","authors":"Kaidi Zhou, Tao Yu, Minxi Wan, Zhengxu Bao, Wenming Bai, Weiliang Wang, Yuanguang Li","doi":"10.1007/s10529-025-03614-3","DOIUrl":"https://doi.org/10.1007/s10529-025-03614-3","url":null,"abstract":"Chlamydomonas reinhardtii CW15, a cell-wall-deficient strain, is a widely used chassis in microalgal genetic engineering. However, its low cell density under autotrophic and mixotrophic cultivation restricts industrial scalability. This study aimed to establish a cost-effective, high-density heterotrophic cultivation process for C. reinhardtii CW15. Initially, an optimized AP medium (Tris-free TAP with K2HPO4 as the sole phosphorus source) significantly reduced medium costs while achieving a cell density of 0.446 g/L. Subsequently, a fed-batch process in a 5 L fermentor yielded a record cell density of 22.1 g/L (growth rate: 94.6 mg/L·h) at 233 h by optimizing nutrient supplementation. Scaling up to a 50 L fermentor revealed challenges in ammonia volatilization and salinity accumulation during sterilization. These were resolved by substituting the nitrogen source with ammonia water and supplementing ammonium acetate as a dual nitrogen and partial carbon source, ultimately achieving 30.2 g/L (140 mg/L·h) after 215 h-the highest reported density for cell-wall-deficient C. reinhardtii. This work provides an efficient and scalable cultivation strategy, facilitating its industrial and biotechnological applications.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"72"},"PeriodicalIF":2.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Role of microbial pesticides in pest control for lepidopteran: research status and prospect. 微生物农药在鳞翅目害虫防治中的作用：研究现状与展望。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-30 DOI: 10.1007/s10529-025-03613-4

LiLi Wei, Yiqing He, Juan Du, Yuejun Fu

引用次数: 0

Nano-enhanced biocarriers: ferric oxide-modified chitosan and calcium alginate beads for improved fermentation efficiency and reusability in a bubble column bioreactor. 纳米强化生物载体：氧化铁修饰壳聚糖和海藻酸钙微球，用于提高气泡柱生物反应器的发酵效率和可重复使用性。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-29 DOI: 10.1007/s10529-025-03611-6

David Abutu, B O Aderemi, A O Ameh, Hafizuddin Wan Yussof, Augustine Agi

{"title":"Nano-enhanced biocarriers: ferric oxide-modified chitosan and calcium alginate beads for improved fermentation efficiency and reusability in a bubble column bioreactor.","authors":"David Abutu, B O Aderemi, A O Ameh, Hafizuddin Wan Yussof, Augustine Agi","doi":"10.1007/s10529-025-03611-6","DOIUrl":"10.1007/s10529-025-03611-6","url":null,"abstract":"Chitosan beads (CB) and calcium alginate beads (CAB) are widely used for immobilizing Saccharomyces cerevisiae in fermentation, but their low mechanical strength and limited surface area reduce ethanol yield. To overcome these limitations, ferric oxide (Fe₂O₃) nanoparticles were incorporated into CB and CAB to enhance both mechanical strength and surface area. The modified carriers were employed for Saccharomyces cerevisiae immobilization in a bubble column bioreactor under semi-batch fermentation conditions at 35 °C, an air flow rate of 0.01 L/min, and pH 4.0 for 15 h. The Fe₂O₃ nanoparticles incorporation significantly improved the rupture forces of CB and CAB, increasing from 2 ± 0.05 N to 8 ± 0.5 N and 2 ± 0.05 N to 9 ± 0.07 N, respectively. The surface area of CB increased from 18 ± 0.3 m2/g to 48 ± 0.2 m2/g, while CAB increased from 2 ± 0.2 m2/g to 50 ± 0.1 m2/g, leading to enhanced cell adsorption from 1.13 × 10⁸ to 1.10 × 10⁹ cells/mL Consequently, ethanol yield improved from 37 ± 0.28% to 45 ± 1.23%. Unlike unmodified CB and CAB, which exhibited significant rupture after five reuse cycles, the modified beads retained their structural integrity and activity, demonstrating their durability for yeast immobilization and reuse. This approach offers a promising strategy for enhancing fermentation efficiency and carrier stability in ethanol production.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"70"},"PeriodicalIF":2.0,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206680/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Target recognition initiated reverse hybridization mediated cascade amplification for sensitive Pseudomonas aeruginosa analysis. 目标识别启动反向杂交介导级联扩增敏感铜绿假单胞菌分析。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-28 DOI: 10.1007/s10529-025-03612-5

Xiaoyan Wang, Jinli Hu

{"title":"Target recognition initiated reverse hybridization mediated cascade amplification for sensitive Pseudomonas aeruginosa analysis.","authors":"Xiaoyan Wang, Jinli Hu","doi":"10.1007/s10529-025-03612-5","DOIUrl":"https://doi.org/10.1007/s10529-025-03612-5","url":null,"abstract":"Pseudomonas aeruginosa (P. aeruginosa) is a significant opportunistic pathogen associated with nosocomial infections, particularly in pediatric populations, where it can lead to severe clinical manifestations, including P. aeruginosa-associated meningitis. To meet the critical need for highly sensitive detection of P. aeruginosa, a novel fluorescent biosensor utilizing a three-way junction (TWJ) probe has been developed. This biosensor capitalizes on the specific binding interaction between P. aeruginosa and a tailored aptamer embedded within a DNA TWJ structure. Upon target binding, the double-stranded DNA branches of the TWJ undergo a conformational rearrangement, resulting in the formation of two distinct DNA \"Y\" junction structures. These structures are subsequently linked by a designed sequence, initiating a DNA polymerase/endonuclease-mediated strand displacement amplification process. The TWJ-based biosensor offers several key advantages: (i) the integration of the aptamer sequence within the TWJ probe ensures high specificity for target recognition, and (ii) the subsequent enzymatic amplification significantly enhances the sensitivity of detection. Under optimized experimental conditions, the biosensor demonstrated a broad linear detection range from 10 to 10 to 105 cfu/mL, with an exceptionally low limit of detection of 4.12 cfu/mL. Recovery studies further confirmed the reliability and robustness, highlighting its potential for clinical implementation. This innovative bio-sensing strategy represents a significant advancement in diagnostic technology, offering a promising tool for the early and accurate detection of infectious diseases in pediatric patients, with potential applications in improving clinical outcomes.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"69"},"PeriodicalIF":2.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Expression of cellulase in Candida glycerogenes and strengthen the expression level for application in residue-containing fermentation to enhance glycerol production. 纤维素酶在产甘油假丝酵母中的表达及强化表达水平，用于含渣发酵提高甘油产量。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-27 DOI: 10.1007/s10529-025-03602-7

Yuxin Gao, Dongqi Jiang, Mengying Wang, Xueqing Du, Hong Zong, Bin Zhuge

{"title":"Expression of cellulase in Candida glycerogenes and strengthen the expression level for application in residue-containing fermentation to enhance glycerol production.","authors":"Yuxin Gao, Dongqi Jiang, Mengying Wang, Xueqing Du, Hong Zong, Bin Zhuge","doi":"10.1007/s10529-025-03602-7","DOIUrl":"https://doi.org/10.1007/s10529-025-03602-7","url":null,"abstract":"Objectives: Expressing cellulase systems in C. glycerinogenes with extracellular secretion ability, and using fermentation with residue, enabled the recombinant strain to degrade lignocellulosic waste for efficient glycerol production, offering new option for agricultural waste transformation.Results: Candida glycerinogenes is employed as the host strain, various cellulases were screened. Signal peptide mining and screening, and semi-rational design strategy was adopted in the host strain. The recombinant strain Cg4 had a total cellulase activity of 13.6 U/mL. Cg4 was applied to 110 g/L sugarcane bagasse hydrolysate with 40 g/L of pretreated bagasse as the substrate. The glycerol yield reached 50 g/L, with a 43.3% bagasse utilization rate, the amount of cellulase used in the degradation of lignocellulose was reduced by 12.1%.Conclusion: Opened up a route for efficient degradation of agricultural waste of lignocellulose by C. glycerinogenes for glycerol production, the emission of lignocellulose waste had been reduced, and decreasing the need for cellulases in hydrolysis.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"68"},"PeriodicalIF":2.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Optimizing hyaluronic acid production by Streptococcus zooepidemicus using taguchi method: effects of temperature and pH. 田口法优化动物流行链球菌生产透明质酸：温度和pH值的影响。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-26 DOI: 10.1007/s10529-025-03608-1

Hilal Girgin Öz, Hamdi Öğüt

{"title":"Optimizing hyaluronic acid production by Streptococcus zooepidemicus using taguchi method: effects of temperature and pH.","authors":"Hilal Girgin Öz, Hamdi Öğüt","doi":"10.1007/s10529-025-03608-1","DOIUrl":"https://doi.org/10.1007/s10529-025-03608-1","url":null,"abstract":"The cost-effective and high-yield production of hyaluronic acid (HA) by microbial means remains challenging, necessitating the optimization of existing processes through the implementation of novel approaches. The present study investigates the production of HA under varying temperature and pH conditions utilizing independent, fully controlled fermenters. The synthesis of HA was evaluated at four temperatures (32 °C, 35 °C, 37 °C, 40 °C) and four pH levels (6.5, 7.0, 7.5, and 8.0), with optimal parameters identified through the Taguchi design methodology. The Taguchi optimization method effectively identified 37 °C and pH 6.5 as the optimal conditions for HA production corresponding to the highest signal-to-noise (S/N) ratios of 58.18 and 57.55, respectively. These conditions resulted in a maximum yield of 1.08 g.L-1, demonstrating the efficacy of this parameter combination in maximizing production efficiency. The carbazole method was utilized to quantify the production of HA following a five-hour fermentation period, with the culture conditions subjected to a statistical comparison. A temperature of 37 °C yielded significantly higher HA levels than 32 °C and 40 °C (Dunn test, respectively p = 0.019, p = 0.001). The lowest HA production was observed at 40 °C, while the 32 °C group exhibited relatively low variation in HA production. Furthermore, the hourly bacterial counts demonstrated a direct correlation between bacterial proliferation and HA synthesis, with the highest bacterial growth observed at 37 °C and pH 7.0. This study highlights the trends in HA concentration under different temperature and pH conditions during the pre-fermentation phase, offering critical insights for optimizing HA production.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"67"},"PeriodicalIF":2.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Engineered β-galactosidase catalyzes lactose to prebiotics in situ in raw milk. 工程β-半乳糖苷酶在原乳中原位催化乳糖生成益生元。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-24 DOI: 10.1007/s10529-025-03601-8

Jihua Zhao, Dandan Niu, Zhuolin Jin, Jiaqi Liu, Dan Ni, Nokuthula Peace Mchunu, Ruyi Fan, Suren Singh, Zhengxiang Wang

{"title":"Engineered β-galactosidase catalyzes lactose to prebiotics in situ in raw milk.","authors":"Jihua Zhao, Dandan Niu, Zhuolin Jin, Jiaqi Liu, Dan Ni, Nokuthula Peace Mchunu, Ruyi Fan, Suren Singh, Zhengxiang Wang","doi":"10.1007/s10529-025-03601-8","DOIUrl":"10.1007/s10529-025-03601-8","url":null,"abstract":"The enzymatic conversion of lactose to galactooligosaccharides (GOS) within raw milk offers a promising avenue for reducing lactose content while enhancing its prebiotic benefits. This process hinges on utilizing enzymes with high transglycosylation activity compatible with current milk processing methods. In the present studies, Bacillus circulans β-galactosidase (BglD) was identified as an effective enzyme, achieving a lactose conversion rate of 73.61% in milk. However, BglD's resistance to pasteurization underscored the need for enzyme modifications. Through molecular directed evolution, a mutant T473L/R484P was engineered. It exhibited improved catalytic performance at lower temperatures, with optimal activity at pH 6.5 and 55 °C. In contrary to the wild-type, mutant T473L/R484P exhibited reduced thermostability, and its activity diminished rapidly above 50 °C. Remarkably, in simulated dairy environments, mutant T473L/R484P converted over 78% to 82% of lactose at low temperatures (5 to 10 °C), reducing lactose to around 10.4 to13.0 g/L while generating approximately 30 to 34 g/L of GOS. These findings highlight the mutant's potential in producing low-lactose, GOS-enriched milk, and pave the way for innovative in situ lactose-to-GOS conversion processes in raw milk.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"66"},"PeriodicalIF":2.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Measurement of HbA1c with a new phase function using RBC phase image from a low-cost digital holographic microscopy. 利用低成本数字全息显微镜的RBC相位图像，用新的相位函数测量HbA1c。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-23 DOI: 10.1007/s10529-025-03610-7

Ashok Kumar Sahu, Bandita Panda, Adik Amiyan Tripathy, Sandip Kumar Dash, Atanu Kumar Bal, Naba Kishor Sahoo, Sukanta Kumar Tripathy

{"title":"Measurement of HbA1c with a new phase function using RBC phase image from a low-cost digital holographic microscopy.","authors":"Ashok Kumar Sahu, Bandita Panda, Adik Amiyan Tripathy, Sandip Kumar Dash, Atanu Kumar Bal, Naba Kishor Sahoo, Sukanta Kumar Tripathy","doi":"10.1007/s10529-025-03610-7","DOIUrl":"10.1007/s10529-025-03610-7","url":null,"abstract":"Objective: Development of a new phase function for measuring HbA1c, using a low-cost digital holographic microscopy to monitor the glucose level in diabetes.Results: Here, we propose a new parameter, <math><msub><mtext>Ø</mtext> <mrow><mi>cp</mi></mrow> </msub> </math> based on two different phases of RBCs, one, the absolute phase at the center, <math><msub><mtext>Ø</mtext> <mi>c</mi></msub> </math> and the other, the average phase at the periphery, <math><msub><mtext>Ø</mtext> <mi>p</mi></msub> </math> . The <math><msub><mtext>Ø</mtext> <mrow><mi>cp</mi></mrow> </msub> </math> value varied almost linearly (R2 = 0.952) with HbA1c (%) in the blood. We used a low-cost digital holographic microscope (DHM) to record the hologram of RBCs, followed by digital reconstruction with the help of our newly introduced code. The critical value of <math><msub><mtext>Ø</mtext> <mrow><mi>cp</mi></mrow> </msub> </math> at 3.5 was found to be equivalent to 6.5% HbA1c in high-performance liquid chromatography (HPLC), beyond which indicates hyperglycemia.Conclusion: The method can be used for large-scale and low-cost estimation of HbA1c (%) with <math><msub><mtext>Ø</mtext> <mrow><mi>cp</mi></mrow> </msub> </math> of ≥ 3.5.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"65"},"PeriodicalIF":2.0,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

2,4-Diacetylphloroglucinol from multi-stress tolerant Pseudomonas guariconensis VDA8: Seed-applied bioprotectant for groundnut (Arachis hypogaea L.) against Aspergillus flavus NCIM 524 for post-harvest preservation. 2,4-二乙酰间苯三酚：花生（Arachis hypogaea L.）抗黄曲霉NCIM 524的种用生物保护剂。

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-17 DOI: 10.1007/s10529-025-03606-3

Raksha A Kankariya, Ambalal B Chaudhari, Navin D Dandi

{"title":"2,4-Diacetylphloroglucinol from multi-stress tolerant Pseudomonas guariconensis VDA8: Seed-applied bioprotectant for groundnut (Arachis hypogaea L.) against Aspergillus flavus NCIM 524 for post-harvest preservation.","authors":"Raksha A Kankariya, Ambalal B Chaudhari, Navin D Dandi","doi":"10.1007/s10529-025-03606-3","DOIUrl":"https://doi.org/10.1007/s10529-025-03606-3","url":null,"abstract":"The fungal contaminated crops or post-harvest products are unfit for consumption, hazardous to human health and threat to food safety. Soil borne phytopathogenic microbes cause severe yield losses at various stages and contribute to 40-50% crop mortality. Post-harvest fungal deterioration during storage is frequently observed primarily because of high oil content. At present, chemical disinfectants and agrichemicals are extensively used to control seed contaminating fungal infection as seed priming agent and/or post-harvest storage protectants. However, application of synthetic fungicides requires experimental evaluation of several parameters and raised serious concerns about emergence of fungicide resistance. On this streak, natural anti-microbial agents such as microbial secondary metabolites are preferred as eco-friendly and cost-effective alternative for seed protection. For this purpose, the use of broad-spectrum antibiotics such as 2,4-diacetylphloroglucinol can warrant potential benefit for seed priming over chemical fungicides. In the present study, it showed maximum inhibitory activity against aflatoxin producing Aspergillus flavus as well as other phytopathogenic fungi viz. Ustilago maydis, Fusarium oxysporum, Sclerotinia sclerotiorum, Colletotrichum circinans and Colletotrichum dematium. It was therefore explored for seed priming of groundnut for repressed proliferation of mycotoxin producing A. flavus. Under pot experiments, 2,4-diacetylphloroglucinol primed seeds showed long-term post-harvest preservation, enhanced seed germination and growth indices as compared to methanol primed and non-primed seeds. 2,4-diacetylphloroglucinol priming is therefore, proposed as a low-cost, dual-benefit seed storage protectant for control of post-harvest fungal deterioration of oilseeds as well as a phytostimulant for enhanced plant growth in field after long-term storage.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 4","pages":"64"},"PeriodicalIF":2.0,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Discovery of novel compound IGYZT01060 for inhibition of IRAK-4 enzyme for the treatment of sepsis. 发现抑制IRAK-4酶治疗败血症的新化合物IGYZT01060

IF 2 4区生物学

Biotechnology Letters Pub Date : 2025-06-14 DOI: 10.1007/s10529-025-03604-5

Deepali Shrivastava, Lavleen K Gupta, Adinarayana Reddy Yerrapureddy, Sampath Kumar Nune Satya

{"title":"Discovery of novel compound IGYZT01060 for inhibition of IRAK-4 enzyme for the treatment of sepsis.","authors":"Deepali Shrivastava, Lavleen K Gupta, Adinarayana Reddy Yerrapureddy, Sampath Kumar Nune Satya","doi":"10.1007/s10529-025-03604-5","DOIUrl":"10.1007/s10529-025-03604-5","url":null,"abstract":"Purpose: This study aimed at the discovery of a novel chemical entity, IGYZT01060 for inhibiting IRAK-4 (Interleukin-1 receptor-associated kinase 4) and testing its ability to inhibit the IRAK-4 enzyme, that is crucial in the context of sepsis due to its central role in the innate immune response, particularly in mediating inflammatory signals from Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs).Methods: This study explores the synthesis and characterization of a novel compound, IGYZT01060, designed to inhibit IRAK-4. The inhibitory analysis was carried out in silico, in vitro and in vivo. Molecular docking was done using AutoDock software. The in vitro assays were carried out in LPS induced THP-1 cells. ADME assays were carried out for understanding the drug delivery and distribution pattern. Lastly, in vivo mice sepsis model using intraperitoneally administered LPS and orally administered compound IGYZT01060 was studied estimate the efficacy of compound IGYZT01060.Results: In silico docking analyses demonstrated a high affinity of IGYZT01060 for IRAK-4, with target prediction indicating a preference for kinase enzymes. The NMR spectroscopy confirmed the successful synthesis and purity of the compound. In vitro studies revealed that IGYZT01060 effectively inhibits IRAK-4 with an IC50 of less than 100 nM. Pharmacokinetic evaluations indicated a favorable clearance rate and high bioavailability, essential for the therapeutic efficacy of any drug. Furthermore, the mice sepsis model results indicated a significant inhibition of IRAK-4, almost as good as the corticosteroid dexamethasone.Conclusion: The promising IRAK-4 inhibition demonstrated by our compound IGYZT01060, along with its favourable pharmacokinetic profile and significant efficacy in a mice sepsis model, highlights its potential as a powerful therapeutic option for treating inflammatory conditions.","PeriodicalId":8929,"journal":{"name":"Biotechnology Letters","volume":"47 3","pages":"62"},"PeriodicalIF":2.0,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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