Biotechnology and Bioengineering最新文献

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Screening and Engineering of Hyperactive Yeast Aquaporins for Xylitol Transport Using Biosensors. 利用生物传感器筛选木糖醇运输的高活性酵母水通道蛋白及其工程研究。
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70227
Lobke Maria Sips, Liam Richard Jenkins Sánchez, Jens Coture, Inge Noëlle Adriënne Van Bogaert
{"title":"Screening and Engineering of Hyperactive Yeast Aquaporins for Xylitol Transport Using Biosensors.","authors":"Lobke Maria Sips, Liam Richard Jenkins Sánchez, Jens Coture, Inge Noëlle Adriënne Van Bogaert","doi":"10.1002/bit.70227","DOIUrl":"https://doi.org/10.1002/bit.70227","url":null,"abstract":"<p><p>Microbial cell factories provide a sustainable platform for producing valuable compounds from renewable substrates. However, the transport of metabolites-particularly the import of substrates and the export of products-remains a major bottleneck in improving production efficiency. Aquaglyceroporins (AQGPs), a subgroup of aquaporins, are small, structurally conserved and energy-independent membrane channels that represent promising targets to overcome this limitation. Yeast AQGPs, known as Fps1, contain extended N- and C-terminal cytosolic regions that play essential roles in channel regulation. Previous studies have suggested that deletion of short conserved motifs within these termini can render Fps1 hyperactive, but this has only been studied in yeast systems and primarily in the context of glycerol. We further explored this phenomenon in the context of xylitol transport, and developed an E. coli-based biosensor to evaluate AQGP-mediated xylitol import. Using this biosensor, truncated variants of Fps1 homologs from Saccharomyces cerevisiae, Kluyveromyces marxianus and Yarrowia lipolytica were evaluated. Two hyperactive variants, ScFps1.4 and KmFps1.2, were identified, revealing aquaglyceroporin- and host-dependent effects on AQGP activity. These findings provide new insights into aquaglyceroporin regulation and its potential for improving metabolite transport in microbial cell factories.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833598","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
Engineering Murine Cross-Reactivity Into an Affibody to Human Death Receptor 5. 工程小鼠交叉反应成人类死亡受体的附着体
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-05-06 DOI: 10.1002/bit.70216
Tse-Han Kuo, Nagamani Vunnam, Jonathan N Sachs, Benjamin J Hackel
{"title":"Engineering Murine Cross-Reactivity Into an Affibody to Human Death Receptor 5.","authors":"Tse-Han Kuo, Nagamani Vunnam, Jonathan N Sachs, Benjamin J Hackel","doi":"10.1002/bit.70216","DOIUrl":"https://doi.org/10.1002/bit.70216","url":null,"abstract":"<p><p>Interspecies cross-reactive protein therapeutics that target conserved epitopes across species are critical for translational research. The present study showcases the engineering of an affibody molecule, originally discovered for binding to human death receptor 5 (hDR5) with 94 nM affinity, to simultaneously acquire cross-reactivity to murine DR5 and enhance its binding affinity to human DR5. DR5 plays a pivotal role in metabolic dysfunction-associated steatohepatitis (MASH) by mediating hepatocyte apoptosis and inflammation. Utilizing a rationally designed library guided by enrichment information and a helix-walking mutagenesis strategy, combined with alternating binding selections between human and murine DR5, we evolved affibody variants exhibiting significantly improved binding to both receptors. Deep sequencing revealed amino acid preferences in the paratope, and the dominant variant, ABY<sub>DR5-A</sub>, demonstrated over 1000-fold and 16-fold affinity improvements to murine and human DR5, respectively, with equilibrium dissociation constants of 15 and 5.8 nM. ABY<sub>DR5-A</sub> exhibited nanomolar IC<sub>50</sub> values for antagonism of TRAIL-induced DR5 signaling, measured via caspase 8 activation, in both murine and human cells, albeit with incomplete inhibition. This engineered affibody provides a promising candidate for therapeutic development targeting DR5-mediated liver disease. Further functional characterization and pharmacokinetic optimization are required to advance these findings toward preclinical evaluation in murine MASH models and, ultimately, clinical applications.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833641","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
Impact of Heavy Chain C-Terminal Codons on Recombinant Monoclonal Antibody Expression Levels. 重链c端密码子对重组单克隆抗体表达水平的影响
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-05-02 DOI: 10.1002/bit.70223
Kenneth R Carlson, Sowmya Balasubramanian, John Herrington, Chris C Frye, Ronan M Kelly
{"title":"Impact of Heavy Chain C-Terminal Codons on Recombinant Monoclonal Antibody Expression Levels.","authors":"Kenneth R Carlson, Sowmya Balasubramanian, John Herrington, Chris C Frye, Ronan M Kelly","doi":"10.1002/bit.70223","DOIUrl":"https://doi.org/10.1002/bit.70223","url":null,"abstract":"<p><p>Advances in process optimization and stable CHO cell line engineering have enabled recombinant monoclonal antibody (mAb) titers above 10 g/L in fed-batch cultures. Despite these advances, the correlation between mAb nucleotide coding sequence and protein yield is still not fully understood. Initial studies with two IgG1 mAbs showed that Lys codon selection at the heavy chain (HC) C-terminus significantly affected yields in certain sequence contexts, as the titer of mAb1 was unchanged by codon selection, while mAb2 titer dropped four-fold with AAG<sup>Lys</sup> compared to AAA<sup>Lys</sup>. To determine the factors contributing to this difference, CHO cell lines expressing the two mAb variants with different HC C-terminal variants were generated. The specific C-terminal codon pair GGT<sup>Gly</sup>-AAG<sup>Lys</sup> notably reduced HC mRNA transcript levels and mAb yields in CHO expression studies. Metabolic labeling studies using a modified uracil analog revealed that the decreased HC transcript levels resulted from reduced accumulation of nascent HC mRNA. Furthermore, the C-terminal codon pair GGT<sup>Gly</sup>-AAG<sup>Lys</sup> was found to broadly influence the expression of other industrially relevant IgG mAb isotypes, including IgG2 and IgG4. This study establishes a connection between the HC C-terminal nucleotide sequence and mAb expression titer, offering insights for optimizing the expression of Fc-containing molecules.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811209","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
Thermodynamic Evaluation of Dual Substrate Growth. 双衬底生长的热力学评价。
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-05-02 DOI: 10.1002/bit.70217
Marit A Verheijen, Tim Meyboom, Mark C M van Loosdrecht, Rebeca Gonzalez-Cabaleiro
{"title":"Thermodynamic Evaluation of Dual Substrate Growth.","authors":"Marit A Verheijen, Tim Meyboom, Mark C M van Loosdrecht, Rebeca Gonzalez-Cabaleiro","doi":"10.1002/bit.70217","DOIUrl":"https://doi.org/10.1002/bit.70217","url":null,"abstract":"<p><p>Various C₁-C₂ compounds are increasingly available through electrochemical reduction of CO<sub>2</sub>. Although not always suitable as a sole substrate, these compounds can supplement a primary substrate like glucose to enhance microbial growth. Yet, the mechanisms underlying the effects of dual substrate consumption on growth rate and growth yield remain poorly understood. We developed a generalized, species-agnostic thermodynamic framework to partition anabolic and catabolic fluxes for various glucose/secondary substrate combinations, predicting maximum growth rate and growth yield as a function of the substrate ratio. The optimal strategy is to use the secondary substrate as electron donor, conserving the most efficient carbon source, glucose, for assimilation. Because many substrates yield similar energy per electron, biomass yield remains constant until glucose becomes limiting for anabolism. When further lowering the glucose fraction, additional assimilation of the auxiliary carbon source reduces the yield. The growth rate follows similar trends. Dual substrate growth enables generalists to produce more biomass from the total resource pool than a combination of specialists, conferring a competitive edge under substrate-limiting conditions. These theoretical observations align with experimental observations of lower residual substrate concentrations and dominance of generalists in natural and engineered oligotrophic environments.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811131","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
Impact of Adeno-Associated Virus Production on Capsid Heterogeneity and Product Quality. 腺相关病毒生产对衣壳异质性和产品质量的影响。
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-05-02 DOI: 10.1002/bit.70219
Alex Meola, Xiaotong Fu, Sarah Laughlin, Thomas Thiers, Luke Mustich, Eli Wiberg, Yongseok Kim, Qi Zhang, Eugenia Fandunyan, Richa Jaiswal, Matt Perez, Ben Rogers, Evan DaSilva, David Rouleau, Rudenc Lushi, Rob Horton, Brian Brazell, Michael Mercaldi, Jin Yin, James McGivney, Ify Iwuchukwu
{"title":"Impact of Adeno-Associated Virus Production on Capsid Heterogeneity and Product Quality.","authors":"Alex Meola, Xiaotong Fu, Sarah Laughlin, Thomas Thiers, Luke Mustich, Eli Wiberg, Yongseok Kim, Qi Zhang, Eugenia Fandunyan, Richa Jaiswal, Matt Perez, Ben Rogers, Evan DaSilva, David Rouleau, Rudenc Lushi, Rob Horton, Brian Brazell, Michael Mercaldi, Jin Yin, James McGivney, Ify Iwuchukwu","doi":"10.1002/bit.70219","DOIUrl":"https://doi.org/10.1002/bit.70219","url":null,"abstract":"<p><p>Adeno-associated virus (AAV) capsids are inherently heterogeneous, arising from viral protein stoichiometric assembly, post-translational modifications, genome packaging, and manufacturing process conditions. Understanding how AAV manufacturing processes affect capsid heterogeneity and corresponding drug product quality impact is essential for AAV-based gene therapies. We investigated the effects of extended production duration and capsid localization at harvest on capsid heterogeneity. Analytical characterization revealed that prolonged production increased extracellular AAV concentrations but also elevated the proportion of empty capsids, overall hydrophobicity, and deamidation of viral protein (VP). These changes altered charge-dependent separation during anion exchange chromatography (AEX). Capsids derived from intracellular fractions showed even higher levels of deamidation and empty particles compared to extracellular populations, further impacting AEX purification performance. Collectively, these findings demonstrate that both production time and capsid localization significantly influence AAV purification process performance and critical quality attributes. Process control strategies to minimize capsid heterogeneity are consequently critical to ensure a consistent quality profile in AAV manufacturing.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811154","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
Engineered B7-H3 Binding in Modular Gp2 Miniproteins. B7-H3在模块化Gp2 miniprotein中的结合。
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-04-29 DOI: 10.1002/bit.70221
Abbigael Harthorn, Hannah K Windsor, Zachary Schmitz, Nathaniel Cheung, Ebube Agwaramgbo, Benjamin J Hackel
{"title":"Engineered B7-H3 Binding in Modular Gp2 Miniproteins.","authors":"Abbigael Harthorn, Hannah K Windsor, Zachary Schmitz, Nathaniel Cheung, Ebube Agwaramgbo, Benjamin J Hackel","doi":"10.1002/bit.70221","DOIUrl":"10.1002/bit.70221","url":null,"abstract":"<p><p>B7-H3, an important immune checkpoint modulator of T-cell function, is a tumor vasculature biomarker and is overexpressed in a variety of cancers. Its expression is associated with tumor growth, metastasis, and poor clinical prognosis, which makes B7-H3 an appealing target for diagnostics and therapeutics. High-affinity, specific, modular ligands are needed to achieve the various modes of molecular targeting strategies. A designed combinatorial library of the small (45 amino acid) Gp2 scaffold was sorted for binders to B7-H3 via yeast surface display with magnetic and flow cytometric cell sorting. Select variants were sequenced, characterized for binding affinity and specificity to B7-H3, and assessed for modularity in a protein-protein fusion. Protein ligands achieved single-digit nanomolar affinities and retained binding affinity upon conjugation, via a glycine-rich linker, to an enzyme. Directed evolution resulted in a potent, 0.7 nM binder with increased stability as assessed through the apparent midpoint of denaturation of 67°C. The engineered ligands provide small, modular, high-affinity B7-H3 binders for molecularly targeted therapeutics and diagnostics.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762520","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
Recent Advances in Laccase-Based Nanobiocatalysts for Sustainable Bioremediation Applications. 漆酶基纳米生物催化剂在可持续生物修复中的应用研究进展。
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-04-29 DOI: 10.1002/bit.70210
Bandana Thakur, Ashok Kumar Nadda, Anil Kant
{"title":"Recent Advances in Laccase-Based Nanobiocatalysts for Sustainable Bioremediation Applications.","authors":"Bandana Thakur, Ashok Kumar Nadda, Anil Kant","doi":"10.1002/bit.70210","DOIUrl":"https://doi.org/10.1002/bit.70210","url":null,"abstract":"<p><p>Laccases are the most common multicopper oxidase (EC 1.10.3.2); as a result, they have attracted great interest as natural cleaners for environmental bioremediation purposes. However, the fragile structure and low recyclability of laccases, along with their high price, are constraints in practical applications. Enzyme immobilization has been identified as one of the best strategies to circumvent these problems and the application of nanomaterials for enzyme immobilization has resulted in nanobiocatalysts (NBCs). Nanomaterials have great advantages for the immobilization of enzymes attributed to their special chemical and physical properties, including large specific surface area, tunable pore size, and strong solid mechanical stability. With better stability, efficacy and specificity, these nano-engineered systems have been very successful in the treatment of a variety of pollutants ranging from persistent organic pollutants and emerging contaminations to industrial waste. Herein, we give an updated review of the most recent advances in laccase-based NBCs, with a particular focus on new strategies for nanomaterial functionalization and laccase enzyme immobilization. Additionally, this review aims to gather information about laccase's sources, mechanisms of action, substrates, and mediators, providing a useful point of reference. This review also compiles numerous recent discoveries about the biology of laccase and its applications as a nanobiocatalyst and provides a concise synopsis that aids researchers in comprehending its possibilities. It also emphasizes the possible use of laccase-based NBCs for bioremediation, especially in dealing with emerging pollutants (EPs) like antibiotics, pharmaceutical residues, textile effluents, and other xenobiotics.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762533","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
Raman Spectroscopy-Based Glucose Feed Control Automates Malic Acid Fermentation. 基于拉曼光谱的葡萄糖饲料控制自动化苹果酸发酵。
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-04-29 DOI: 10.1002/bit.70211
Luca Antonia Grebe, Katharina Hürter, Dominik Engel, Alexander Walter Wilhelm Echtermeyer, Mafalda S Santos, Laurin Röder, Valentin Steier, Jörn Viell, Jørgen Barsett Magnus
{"title":"Raman Spectroscopy-Based Glucose Feed Control Automates Malic Acid Fermentation.","authors":"Luca Antonia Grebe, Katharina Hürter, Dominik Engel, Alexander Walter Wilhelm Echtermeyer, Mafalda S Santos, Laurin Röder, Valentin Steier, Jörn Viell, Jørgen Barsett Magnus","doi":"10.1002/bit.70211","DOIUrl":"https://doi.org/10.1002/bit.70211","url":null,"abstract":"<p><p>Fermentation optimization and automation are essential for advancing biotechnology's economic viability. A key aspect is maintaining optimal substrate availability; nevertheless, traditional substrate feeding often leads to imprecise control or carbon limitation due to a lack of online monitoring. This work introduces Raman spectroscopy for closed-loop glucose feed control during malic acid production, a promising platform chemical with diverse applications in food, pharmaceuticals, and biodegradable plastics. The production host Ustilago trichophora displays maximal productivity at substrate concentrations well above the substrate affinity constant; however, the feed rate is severely affected by biomass growth, cell aging, or product inhibition. Real-time online monitoring of glucose and malic acid concentrations is achieved using a Partial Least Squares regression model, with a root mean square error of prediction of 2.7 g/L and 5.3 g/L, respectively. The implemented automated feedback system uses a PID controller that dynamically adjusts the feed rate based on real-time metabolic demands to maintain a constant glucose concentration at 20 g/L during the production phase. Simultaneously, the product concentration is monitored, and the feed is stopped automatically to prevent substrate loss due to product inhibition. This work highlights the practical relevance of Raman-based fermentation control, extending its significance beyond mere technical feasibility.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762492","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
Nicotinamide Reverses the Warburg Effect in CHO Cell Culture. 烟酰胺逆转CHO细胞培养中的Warburg效应。
IF 3.6 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-04-29 DOI: 10.1002/bit.70224
James Morrissey, Ayca Cankorur-Cetinkaya, Luigi Grassi, Annie J Harwood-Stamper, Jonathan Welsh, Ryte Poskute, Kasia Kozakowska-McDonnell, Cleo Kontoravdi
{"title":"Nicotinamide Reverses the Warburg Effect in CHO Cell Culture.","authors":"James Morrissey, Ayca Cankorur-Cetinkaya, Luigi Grassi, Annie J Harwood-Stamper, Jonathan Welsh, Ryte Poskute, Kasia Kozakowska-McDonnell, Cleo Kontoravdi","doi":"10.1002/bit.70224","DOIUrl":"10.1002/bit.70224","url":null,"abstract":"<p><p>The Warburg effect, the preferential conversion of glucose-derived pyruvat to lactate despite available oxygen, is a key feature of Chinese hamster ovary (CHO) cell culture. Lactate accumulation in recombinant protein-producing cell culture is an inefficient usage of glucose, as well as being deleterious to cells. Lactate accumulation lowers culture pH, requiring base addition to maintain bioreactor pH setpoint, which subsequently leads to hyperosmolarity, adversely impacting cell growth, productivity and product quality. A key driver for the Warburg effect, and hence lactate accumulation, is the need to regenerate NAD<sup>+</sup> consumed during glycolysis. Since oxidative phosphorylation has limited capacity to recycle NADH back to NAD<sup>+</sup> at high glycolytic fluxes, cells rely on lactate dehydrogenase (LDH) to convert pyruvat to lactate, simultaneously regenerating NAD<sup>+</sup> and sustaining glycolysis. Thus, providing the cells' capacity to generate more NAD<sup>+</sup> would decrease the reliance on the Warburg effect. In this study, feeding the NAD<sup>+</sup> precursor nicotinamide (NAM) leads to reversal of the Warburg effect, inducing the \"lactate shift\" 3 days earlier in cell culture and reducing peak lactate concentration by 40%. Transcriptomic analysis further confirms this metabolic shift, with an upregulation of key mitochondrial electron transport chain genes. NAM supplementation increased Fc galactosylation without affecting fucosylation, sialylation, or high-mannose species. These results identify NAD<sup>+</sup>/NADH balance as a key regulator of the Warburg effect and demonstrate NAM supplementation as a simple, cost-effective strategy to mitigate lactate accumulation and improve metabolic efficiency in CHO cell cultures.</p>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762458","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
Impact of Agitation Power Input on Aspergillus oryzae Metabolism: Application of Multi-Omics on an Industrial Enzyme Fermentation. 搅拌功率输入对米曲霉代谢的影响:多组学在工业酶发酵中的应用。
IF 3.8 2区 生物学
Biotechnology and Bioengineering Pub Date : 2026-04-23 DOI: 10.1002/bit.70214
Mariana Albino,Jean-Marie Mouillon,Gisela Nadal-Rey,Carina L Gargalo,Ulrich Krühne,Krist V Gernaey,Mads O Albæk
{"title":"Impact of Agitation Power Input on Aspergillus oryzae Metabolism: Application of Multi-Omics on an Industrial Enzyme Fermentation.","authors":"Mariana Albino,Jean-Marie Mouillon,Gisela Nadal-Rey,Carina L Gargalo,Ulrich Krühne,Krist V Gernaey,Mads O Albæk","doi":"10.1002/bit.70214","DOIUrl":"https://doi.org/10.1002/bit.70214","url":null,"abstract":"The agitation power input substantially impacts the oxygen transfer rate in aerobic fermentation processes. Furthermore, in a carbon-limited process where the substrate feed rate is controlled by the concentration of dissolved oxygen, the power input will consequently govern the feed rate. Thus, these external design factors affect the cell metabolic rates significantly. We aim to investigate the impact of different power input levels, 11.6 and 2.2 kW/m3, on the microorganism's cellular metabolism by applying proteomics and transcriptomics analyses on a pilot-scale (550 L) enzyme-producing Aspergillus oryzae fermentation process. Transcriptomics results indicate differences in carbon metabolism regulation and nutrient uptake in two different power input levels, with upregulation of carbon and ammonia transporters and downregulation of phosphate transporters in the lower power input level. Proteasome analysis reveals significant differences in ribosome-associated proteins, corroborating higher product yield on substrate in the lower power input batches. This multi-omics approach allows the identification of key metabolic differences that standard process characterization methods, such as cell dry weight quantification and off-gas analyses, cannot capture. The study also demonstrates the potential of omics-focused sampling techniques on a pilot (or production) scale for in-depth process understanding and, therefore, further optimization of fermentation processes.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"18 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147735203","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
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