Enzyme and Microbial Technology最新文献

{"title":"Cell surface display of CAL-B in Escherichia coli using the split GFP system","authors":"Jisoo Lee,&nbsp;Jong-In Won","doi":"10.1016/j.enzmictec.2025.110726","DOIUrl":"10.1016/j.enzmictec.2025.110726","url":null,"abstract":"<div><div>Bacterial surface display systems enable the immobilization of proteins on the outer membrane for applications such as peptide library screening, biosensing, and bioadsorption. However, the display efficiency of large proteins remains limited, primarily due to challenges in translocating bulky polypeptides across the membrane. To address this, a split Green Fluorescent Protein (split GFP)-based strategy was evaluated. This method employs two non-fluorescent GFP fragments—GFP11 and GFP1–10—that reassemble into a fluorescent complex when co-localized. In this study, the small GFP fragment (GFP11) was genetically fused to Lipoprotein-Outer Membrane Protein A (Lpp-OmpA) to promote membrane anchoring, while the large GFP fragment (GFP1–10) was fused to <em>Candida antarctica</em> lipase B (CAL-B). The CAL-B-GFP1–10 fusion protein was expressed separately and then incubated with cells displaying Lpp-OmpA-GFP11, facilitating potential reassembly on the cell surface. Restoration of fluorescence served as an indirect indicator of successful surface localization. Enzymatic assays were also performed to compare the activity of CAL-B displayed via the split GFP system versus conventional direct fusion to Lpp-OmpA. The results demonstrated that the split GFP approach can enhance surface display and preserve enzymatic function, offering a promising alternative for displaying large or structurally complex proteins. While further optimization is needed, these findings support the potential of split GFP-assisted strategies in expanding the scope of bacterial surface display applications.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110726"},"PeriodicalIF":3.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144750830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of natively expressed chitinase as a sustainable fungal bioshield","authors":"Farah Deeba ,&nbsp;Tarek E. Mazeed ,&nbsp;Davita L. Watkins ,&nbsp;Chad A. Rappleye ,&nbsp;David W. Wood","doi":"10.1016/j.enzmictec.2025.110727","DOIUrl":"10.1016/j.enzmictec.2025.110727","url":null,"abstract":"<div><div>Postharvest losses of fruits and vegetables due to fungal spoilage pose a significant challenge, compounded by growing consumer concerns about the harmful effects of chemical fungicides and the limited effectiveness of traditional food coatings (such as wax and biopolymer formulations) in controlling microorganisms, particularly fungi. In this study, we developed a formulation-free method using a non-modified chitinase from a thermostable strain of <em>Bacillus cereus</em> isolated from soil. The purified chitinase inhibited in vitro mycelium growth of four food-pathogenic fungi: <em>Penicillium digitatum</em>, <em>Neurospora crassa</em>, <em>Aspergillus fumigatus</em>, and <em>Alternaria alternata</em>. Furthermore, when applied directly on strawberry and onion tissue, the purified chitinase inhibited <em>Aspergillus fumigatus</em> and <em>A. niger</em> colonization of the produce. This demonstrates the addition of chitinase provides a cost-effective and non-toxic alternative as a bio-active food coating material to prevent fungal fruit and vegetable spoilage and extend food shelf life.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110727"},"PeriodicalIF":3.7,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144766999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and recombinant expression of a novel defluorinase from Rhodococcus jostii RHA1, for defluorination and biotransformation of the PFAS compound 6:2 fluorotelomer carboxylic acid","authors":"Eustace Y. Fernando","doi":"10.1016/j.enzmictec.2025.110724","DOIUrl":"10.1016/j.enzmictec.2025.110724","url":null,"abstract":"<div><div>Poly and per fluorinated substances (PFAS) are emerging contaminants of concern that are thought to be involved in causing numerous adverse health effects, such as immunosuppression, increased chance of cancer development, and altered levels of hepatic enzyme levels in humans. However, PFAS are considered highly persistent and resistant to biodegradation given the fact that the C-F bond can have a bond dissociation energy of up to 544 kJ/mol. Though many studies have reported PFAS biodefluorination by bacterial isolates and microbial communities, little is known regarding the molecular foundations for biodefluorination. In this study, a novel defluorinase was identified, that is responsible for the biodefluorination of 6:2 fluorotelomer carboxylic acid (6:2 FTCA) in <em>R</em>.<em>jostii</em> RHA1 using the combination of transposome-based insertional mutagenesis and heterologous expression. From a library of 417 <em>R</em>.<em>jostii</em> RHA1. mutants, 3 individual mutants lost their ability for defluorination when they were exposed to 6:2 FTCA (mutant # 15, 32 and 38 – Table S2). The disruption of the genetic locus in all 3 non-defluorinating mutants was identified coding for a putative MhPC superfamily protein. The MhPC superfamily of proteins is known to harbor other proteins such as fluoroacetate dehalogenase (UniProt - Q6NAM1) that are capable of –C-F bond cleavage. This identified gene was cloned into the heterologous expression host <em>M. smegmatis</em> MC²-155. After induction, the <em>M. smegmatis</em> MC²-155 transformant exhibited the ability to defluorinate 6:2 FTCA at a rate of 13 µmol/h (V_max = 80.9 µmol/min and K_m = 5.04 mM in Michaelis-Menten models). In contrast, defluorination was not observed in either abiotic or biotic controls. Further characterization of the novel defluorinase indicated that it could moderately defluorinate the unsaturated PFAS compound 6:2 FTCUA (4.9 µmol/h fluoride) and minimally defluorinate 5:2 sFTOH (1.3 µmol/h fluoride). The novel defluorinase indicated a maximal specific activity of 12.9 ± 1.9 µmol F/hr/g protein, against its primary PFAS substrate, 6:2 FTCA. However, it showed no activity with 5:3 FTCA or sulfonated PFAS compounds such as 6:2 FTS and 8:2 FTS. The wild-type <em>Rhodococcus</em> could defluorinate 6:2 FTCA at a rate of 2.2 µmol/h. The discovery of this MhPC class novel defluorinase in WT <em>R</em>.<em>jostii</em> RHA1. has substantial value since it is responsible for the critical step that initiates defluorination of PFAS compounds such as 6:2 FTCA.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110724"},"PeriodicalIF":3.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced production of hyperthermophilic Pyrococcus furiosus β-glucosidase in Corynebacterium glutamicum by optimization of the promoter, vector backbone, and His-tag location","authors":"Mehmet Emre Erkanli ,&nbsp;Ryu Hong Park ,&nbsp;Jingwei Liu ,&nbsp;Gunhyeong Lee ,&nbsp;Amulya Hota ,&nbsp;Jehyeon Lee ,&nbsp;Chaehyun Ryu ,&nbsp;Ki Jun Jeong ,&nbsp;Jin Ryoun Kim","doi":"10.1016/j.enzmictec.2025.110725","DOIUrl":"10.1016/j.enzmictec.2025.110725","url":null,"abstract":"<div><div>A hyperthermophilic β-glucosidase from <em>Pyrococcus furiosus</em> (PfBGL) is a highly stable and active glycoside hydrolase, well-suited for a wide range of applications. Although PfBGL has been successfully expressed in <em>Escherichia coli</em>, the use of this host limits its applicability in the healthcare and food processing industries due to safety concerns associated with <em>E. coli</em>-based expression systems. Recently, <em>Corynebacterium glutamicum</em> has emerged as a safe and versatile microbial platform for the expression of recombinant proteins used in food processing, pharmaceutical development, therapeutic enzyme production, and probiotic applications. Despite these advantages, heterologous expression in <em>C. glutamicum</em> is often hindered by low protein yields, and PfBGL expression in this host has not been previously explored. In this study, we report for the first time the production of PfBGL in <em>C. glutamicum</em>, achieving a 15-fold enhancement through the optimization of the promoter, the vector backbone, and the His-tag location. Among four different promoters, the <em>P</em>_trc promoter with <em>RBS</em>_T7 yielded the highest PfBGL expression. For the <em>P</em>_trc-<em>RBS</em>_T7 combination, the PfBGL expression levels further varied depending on the vector backbone. Interestingly, placing the His-tag at the N-terminus of PfBGL not only increased its expression in <em>C. glutamicum</em>, but also enhanced its enzymatic activity (<em>k</em>_cat/<em>K</em>_m), when compared to C-terminal tagging. Overall, this study showcases a simple yet effective strategy at both genetic and protein levels to enhance PfBGL production in <em>C. glutamicum</em>, thereby broadening its utility as a host for diverse protein production applications.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110725"},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144724365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the role of catalytic triad Ser-His-Asp on the dynamics of the Lactobacillus helveticus cell-envelope proteinases","authors":"Li Chen ,&nbsp;Ni Lei ,&nbsp;Guanli Du ,&nbsp;He Chen ,&nbsp;Guowei Shu","doi":"10.1016/j.enzmictec.2025.110723","DOIUrl":"10.1016/j.enzmictec.2025.110723","url":null,"abstract":"<div><div>Lactic acid bacterium (LAB) hydrolyzes milk proteins into small bioactive peptides to flourish milk nutrition value. Cell-envelope proteinases (CEPs) are vitally important to bacterial growth, the texture and flavor formation, and the generation of bioactive peptides in fermented milk. Previous literature suggested PR domain of CEP was responsible for the catalytic activity. This study aims to explore the CEP molecular mechanism by delineating the catalytic triad Ser-His-Asp active sites of PR domain in <em>Lactobacillus helveticus</em> CNRZ32 with the aid of homology modeling, molecular docking and dynamics analysis. These results proved that catalytic triads were involved in the PR activation and the catalytic residues Ser608 and His270 appeared to be the core of catalytic process. Our study gained novel insights on the catalytic mechanism of CEP of <em>L. helveticus</em> CNRZ32 which would be a pioneer to facilitate the development of dairy product industry.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110723"},"PeriodicalIF":3.4,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144679800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrated approach based on sequential fractionation and specific enzymatic saccharification of green algae Ulva sp. biomass","authors":"Nesrine Ben Yahmed ,&nbsp;Rahma Masmoudi ,&nbsp;Emna Ben Yahmed ,&nbsp;Cyrine Ben Amor ,&nbsp;Issam Smaali","doi":"10.1016/j.enzmictec.2025.110715","DOIUrl":"10.1016/j.enzmictec.2025.110715","url":null,"abstract":"<div><div>Marine green algae of the <em>genus Ulva</em> are abundant worldwide. In the case of eutrophication, they can be stranded in large quantities, thereby causing ecological and economic problems. Compared to other macroalgae, this biomass remains underexploited on an industrial scale. Thus, the aim of this study was to develop an integrated downstream process applicable to the biomass of the green algae <em>Ulva</em> sp., allowing a major sequential recovery of high-added-value fractions corresponding to pigments, ulvan, alkali-soluble hemicelluloses, and cellulose. Indeed, the proposed concept using cascade extractions enable to produce 0.64 ± 0.16 % of pigments rich in chlorophylls and caroténoids, 28 ± 0.8 % of ulvan, 5 ± 0.3 % of alkali-soluble hemicelluloses and 10 ± 0.4 % of cellulose based on initial dry weight. Characterization of the extracted polysaccharides and verification of their purity were confirmed using FTIR and monosaccharide composition analyses. To better evaluate the biodegradability and the success of the extraction procedure, enzymatic saccharification was applied at the end of the cascade using the cellulose fraction as the substrate. In parallel, saccharification of the total algal biomass was also carried out under the same conditions. Results showed a significant improvement in conversion yields from 74.6 ± 0.85 % to 84 ± 0.7 % showing that <em>Ulva</em>’s cellulose fraction can be a promising candidate for biofuels production. This study presents a sustainable biorefinery approach that allows almost complete fractionation and bioconversion of green macroalgae, and integrates the concept of a circular bio-economy.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110715"},"PeriodicalIF":3.4,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual-acting single-engineered hybrid-architectured promoters enhance and convert expressions into multi-carbon source-regulated systems in Komagataella phaffii","authors":"Beste Avcı ,&nbsp;Pınar Çalık","doi":"10.1016/j.enzmictec.2025.110713","DOIUrl":"10.1016/j.enzmictec.2025.110713","url":null,"abstract":"<div><div>Ethanol, glycerol, methanol, and acetate are sustainable carbon sources (SCSs) used as substrates for biochemical production. Cells are simultaneously exposed not to a single but multiple external stimuli. SCSs as substrates and co-substrates must be directed/redirected into fermentations. We need <em>de novo</em> <strong>e</strong>ngineered <strong>p</strong>romoters inducible with multi-carbon sources. Core to this conceptual advance is the development of novel methodologies for integrating SCSs into fermentations through engineering transcriptional machinery-element interactions with multiple transcriptional switches, each designed with directed transcription factor (TF) binding site (TFBS)-TF interactions in <em>Komagataella phaffii</em> (<em>Pichia pastoris</em>). <strong>D</strong>ual-<strong>a</strong>cting <strong>s</strong>ingle-<strong>e</strong>ngineered <strong>p</strong>romoters (DASEPs) were designed on <em>alcohol dehydrogenase 2</em> (<em>ADH2</em>) hybrid-architectured promoter layout with two directed synthetic TFBS-TF interactions, function as transcriptional switches to drive SCS-induced upregulated- and/or rewired- transcription and expression. Using cross-yeast analogies, we predicted the master TFs <em><strong>(i)</strong></em> Cat8 on ethanol and methanol and <em><strong>(ii)</strong></em> Hap1 and Hap2/3/4/5 complex on the SCSs. Using single-acting single-engineered promoters (SASEPs) carrying synthetic TFBS-Cat8 transcriptional switch constructed on the base promoter <em>ADH2</em> architecture, we generated DASEP₁ and DASEP₂ on the hybrid-architectured SASEP₃ layout with synthetic TFBS-Hap1 and TFBS-Hap2/3/4/5 transcriptional switches, respectively. DASEP₁ and DASEP₂ performances tested by eGFP expression measurements in SCSs, outcompeted SASEPs and compared to SASEP₃, respectively, <em><strong>(i)</strong></em> 8.2- and 6.5-fold on glycerol, <em><strong>(ii)</strong></em> 2.7- and 2.6-fold on 2 % (v/v) ethanol, <em><strong>(iii)</strong></em> 3.9- and 4.0-fold on 1 % (v/v) ethanol, <em><strong>(iv)</strong></em> 3.6- and 4.2-fold on 1 % (v/v) methanol, and <em><strong>(v)</strong></em> 3.7- and 2.8-fold on acetate. In contrast, lower cell concentrations indicated the metabolic burden of eGFP expression on the metabolic engineered <em>K. phaffii</em> cells constructed with DASEPs.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110713"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144721444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of static magnetic field influencing morphogenesis of Flavobacterium sp. m1-14","authors":"Mengxue Zhang ,&nbsp;Peng Wang ,&nbsp;Han Wang ,&nbsp;Li Wang ,&nbsp;Xiumin Ding ,&nbsp;Zhiming Zheng ,&nbsp;Genhai Zhao","doi":"10.1016/j.enzmictec.2025.110714","DOIUrl":"10.1016/j.enzmictec.2025.110714","url":null,"abstract":"<div><div>The biological effects of static magnetic fields (SMF) have long been a research hotspot in academia. While the impact of magnetic fields on microbial morphogenesis is closely linked to microbial fermentation efficiency, the specific mechanism remains incompletely elucidated. In this study, the vitamin K₂-producing strain <em>Flavobacterium sp</em>. m1–14 was exposed to a static magnetic field of up to 9 Tesla (T) for 24 h. It was observed that the bacterial cells shrank, showing an overall decreasing trend in size. The length, width, and aspect ratio decreased by approximately 25.27 %, 14.28 %, and 17.95 %, respectively. Furthermore, the physiological and biochemical properties of the bacteria underwent significant changes. Specifically, the cell membrane permeability increased by approximately 6.2 %; the activities of Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase decreased by about 57.5 % and 34.7 %, respectively; and the membrane potential decreased significantly. In addition, intracellular ATP levels decreased by approximately 12 %, a change directly attributed to impaired ATP metabolism. Investigations into the key morphological regulatory genes <em>mreB</em> and <em>ftsZ</em> revealed that their transcription levels were unregulated by 190 % and 38 %, respectively—likely a stress response induced by cellular energy deficiency. Under conditions of high <em>mreB</em> and <em>ftsZ</em> expression, cells reduce their size to minimize metabolic loss, thereby adapting to extreme environments.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110714"},"PeriodicalIF":3.7,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144720775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new cold-active transglutaminase: Discovery, computational insights, and recombinant expression","authors":"Han Liu ,&nbsp;Saisai Ding ,&nbsp;Corinne Nardin ,&nbsp;Yi Zhang","doi":"10.1016/j.enzmictec.2025.110712","DOIUrl":"10.1016/j.enzmictec.2025.110712","url":null,"abstract":"<div><div>Transglutaminases (TGases) are versatile enzymes widely applied in food, biomedical, and material sciences, but the cold-active TGases are underexplored despite their significance in low-temperature bioprocessing. This study reports the identification, computational characterization, and recombinant expression of a new transglutaminase (akTGase) derived from the Antarctic krill transcriptome. Bioinformatics analysis revealed that akTGase was estimated of 84.76 kDa, possesses structural traits consistent with cold adaptation, including elevated hydrophilicity, high levels of methionine and aspartic acid but low arginine content, and high proportions of flexible regions. Molecular dynamics simulations at 4 °C and 25 °C showed enhanced surface flexibility and conformational stability at low temperature. Recombinant akTGase was produced in <em>E</em>. <em>coli</em>, recovered from inclusion bodies via stepwise dialysis, and assayed for enzymatic activity. The refolded akTGase displayed significantly higher specific activity at 4 °C than at 25 °C, confirming its cold-active nature. This work highlights a successful strategy combining transcriptomic mining, structural prediction, and experimental validation for the discovery of psychrophilic enzymes, particularly TGase, offering promising potential for sustainable applications in cold-adapted biocatalysis.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"191 ","pages":"Article 110712"},"PeriodicalIF":3.4,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulating UDP-glucuronosyltransferase activity: Mechanisms, clinical implications, therapeutic strategies, and future directions in drug development","authors":"Ahmed A. Allam ,&nbsp;Hassan A. Rudayni ,&nbsp;Noha A. Ahmed ,&nbsp;Faris F. Aba Alkhayl ,&nbsp;Al Mokhtar Lamsabhi ,&nbsp;Emadeldin M. Kamel","doi":"10.1016/j.enzmictec.2025.110711","DOIUrl":"10.1016/j.enzmictec.2025.110711","url":null,"abstract":"<div><div>UDP-glucuronosyltransferases (UGTs) are essential enzymes in the phase II metabolism of endogenous and exogenous compounds, playing a critical role in detoxification, drug metabolism, and clearance. Their function is crucial for the pharmacokinetics of numerous therapeutic agents, but UGT inhibition can result in altered drug metabolism, increased toxicity, or reduced efficacy. This review explores the mechanisms of UGT inhibition, its implications for drug metabolism and pharmacokinetics, and the clinical relevance of such inhibition in the context of drug-drug interactions (DDIs). We discuss the therapeutic strategies targeting UGTs, the impact of environmental and dietary factors on UGT activity, and the role of pharmacogenetics in modulating UGT function. Moreover, the review highlights the role of UGTs in xenobiotic detoxification and addresses the challenges in identifying and modulating UGT inhibition in drug development. Finally, we identify future research directions for understanding UGT inhibition and its clinical applications. By synthesizing recent advances in the field, this review provides a comprehensive overview of the dynamic role of UGTs in drug metabolism, offering insights for optimizing drug therapy and minimizing adverse interactions.</div></div>","PeriodicalId":11770,"journal":{"name":"Enzyme and Microbial Technology","volume":"190 ","pages":"Article 110711"},"PeriodicalIF":3.4,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144595702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}