Biotechnology and Bioengineering最新文献

{"title":"Biotechnology and Bioengineering: Volume 122, Number 2, February 2025","authors":"","doi":"10.1002/bit.28742","DOIUrl":"https://doi.org/10.1002/bit.28742","url":null,"abstract":"Click on the article title to read more.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"28 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142940433","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}

{"title":"The Effect of Accessibility of Insoluble Substrate on the Overall Kinetics of Enzymatic Degradation","authors":"Zdeněk Petrášek, Bernd Nidetzky","doi":"10.1002/bit.28921","DOIUrl":"https://doi.org/10.1002/bit.28921","url":null,"abstract":"The enzymatic reaction kinetics on cellulose and other solid substrates is limited by the access of the enzyme to the reactive substrate sites. We introduce a general model in which the reaction rate is determined by the active surface area, and the resulting kinetics consequently reflects the evolving relationship between the exposed substrate surface and the remaining substrate volume. Two factors influencing the overall surface-to-volume ratio are considered: the shape of the substrate particles, characterized by a single numerical parameter related to its dimensionality, and the distribution of the particle sizes. The model is formulated in a form of simple analytical equations, enabling fast and efficient application to experimental data, and facilitating its incorporation into more detailed and complex models. The application of the introduced formalism exploring its potential to account for the observed reaction rate is demonstrated on two examples: the derivation of particle size distribution from experimentally determined reaction kinetics, and the prediction of reaction slowdown from experimental particle size distribution.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"29 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142935059","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}

{"title":"Genome-Scale Community Model-Guided Development of Bacterial Coculture for Lignocellulose Bioconversion","authors":"Pritam Kundu, Amit Ghosh","doi":"10.1002/bit.28918","DOIUrl":"https://doi.org/10.1002/bit.28918","url":null,"abstract":"Microbial communities have shown promising potential in degrading complex biopolymers, producing value-added products through collaborative metabolic functionality. Hence, developing synthetic microbial consortia has become a predominant technique for various biotechnological applications. However, diverse microbial entities in a consortium can engage in distinct biochemical interactions that pose challenges in developing mutualistic communities. Therefore, a systems-level understanding of the inter-microbial metabolic interactions, growth compatibility, and metabolic synergisms is essential for developing effective synthetic consortia. This study demonstrated a genome-scale community modeling approach to assess the inter-microbial interaction pattern and screen metabolically compatible bacterial pairs for designing the lignocellulolytic coculture system. Here, we have investigated the pairwise growth and biochemical synergisms among six termite gut bacterial isolates by implementing flux-based parameters, i.e., pairwise growth support index (PGSI) and metabolic assistance (PMA). Assessment of the PGSI and PMA helps screen nine beneficial bacterial pairs that were validated by designing a coculture experiment with lignocellulosic substrates. For the cocultured bacterial pairs, the experimentally measured enzymatic synergisms (DES) showed good coherence with model-derived biochemical compatibility (PMA), which explains the fidelity of the in silico predictions. The highest degree of enzymatic synergisms has been observed in <i>C. denverensis</i> P3 and <i>Brevibacterium</i> sp P5 coculture, where the total cellulase activity has been increased by 53%. Hence, the flux-based assessment of inter-microbial interactions and metabolic compatibility helps select the best bacterial coculture system with enhanced lignocellulolytic functionality. The flux-based parameters (PGSI and PMA) in the proposed community modeling strategy will help optimize the composition of microbial consortia for developing synthetic microcosms for bioremediation, bioengineering, and biomedical applications.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"43 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142929716","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}

{"title":"A Novel, Site-Specific N-Linked Glycosylation Model Provides Mechanistic Insights Into the Process-Condition Dependent Distinct Fab and Fc Glycosylation of an IgG1 Monoclonal Antibody Produced by CHO VRC01 Cells","authors":"Jayanth Venkatarama Reddy, Thomas Leibiger, Sumit Kumar Singh, Kelvin H. Lee, Eleftherios Papoutsakis, Marianthi Ierapetritou","doi":"10.1002/bit.28916","DOIUrl":"https://doi.org/10.1002/bit.28916","url":null,"abstract":"The CHO VRC01 cell line produces an anti-HIV IgG1 monoclonal antibody containing N-linked glycans on both the Fab (variable) and Fc (constant) regions. Site-specific glycan analysis was used to measure the complex effects of cell culture process conditions on Fab and Fc glycosylation. Experimental data revealed major differences in glycan fractions across the two sites. Bioreactor pH was found to influence fucosylation, galactosylation, and sialylation in the Fab region and galactosylation in the Fc region. To understand the complex effects of process conditions on site-specific N-linked glycosylation, a kinetic model of site-specific N-linked glycosylation was developed. The model parameters provided mechanistic insights into the differences in glycan fractions observed in the Fc and Fab regions. Enzyme activities calculated from the model provided insights into the effect of bioreactor pH on site-specific N-linked glycosylation. Model predictions were experimentally tested by measuring glycosyltransferase-enzyme mRNA-levels and intracellular nucleotide sugar concentrations. The model was used to demonstrate the effect of increasing galactosyltransferase activity on site-specific N-linked glycan fractions. Experiments involving galactose and MnCl₂ supplementation were used to test model predictions. The model is capable of providing insights into experimentally measured data and also of making predictions that can be used to design media supplementation strategies.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"7 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142905038","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}

{"title":"Predictions to Increase Lasso Peptide Production in the Heterologous Host Streptomyces coelicolor M1152","authors":"Valeria Razmilic, Juan A. Asenjo, Irene Martínez","doi":"10.1002/bit.28917","DOIUrl":"https://doi.org/10.1002/bit.28917","url":null,"abstract":"Production of specialized metabolites are restricted to the metabolic capabilities of the organisms. Genome‐scale models (GEM)s are useful to study the whole metabolism and to find metabolic engineering targets to increase the yield of a target compound. In this work we use a modified model of <jats:italic>Streptomyces coelicolor</jats:italic> M145 to simulate the production of lagmysin A (LP4) and the novel lagmysin B (LP2) lasso peptide, in the heterologous host <jats:italic>Streptomyces coelicolor</jats:italic> M1152. Overexpression targets were identified using the flux scanning based on enforced objective flux (FSEOF) algorithm and flux variability analysis (FVA), considering growth in minimum and in complex medium. Thirteen reactions were found as candidate metabolic engineering targets for both lasso peptides considering both settings. We propose the overexpression of enzymes of the glycolysis pathway (GAPD, PGK, PGM and ENO) and leucine biosynthesis (IPPS, IPPMIb, IPPMIa, IPMD and OMCDC) to enhance the production of either lagmysin A or B.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"327 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142901714","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}

{"title":"CFD‐Based Determination of Optimal Design and Operating Conditions of a Fermentation Reactor Using Bayesian Optimization","authors":"Hongbum Choi, Kosan Roh, Jay H. Lee","doi":"10.1002/bit.28912","DOIUrl":"https://doi.org/10.1002/bit.28912","url":null,"abstract":"The efficiency of fermentation reactors is significantly impacted by gas dispersion and concentration distribution, which are influenced by the reactor's design and operating conditions. As the process scales up, optimizing these parameters becomes crucial due to the pronounced concentration gradients that can arise. This study integrates the kinetics of the fermentation process with hydrodynamic analysis using Bayesian optimization to efficiently determine the optimal reactor design and operating conditions. By utilizing computational fluid dynamics (CFD) simulations, the study provides a comprehensive assessment of distributions ranging from gas supply to cell growth. The results demonstrate that a combination of wide baffle width, narrow impeller gap, slow gas flow rate, and high agitation speed significantly enhances reactor performance by improving gas distribution and minimizing stagnant zones. These findings underscore the importance of considering both kinetic and hydrodynamic factors to achieve more precise and scalable fermentation processes, offering valuable insights for industrial applications.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"154 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887941","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}

{"title":"H2 Consumption by Various Acetogenic Bacteria Follows First‐Order Kinetics up to H2 Saturation","authors":"Laura Muñoz‐Duarte, Susmit Chakraborty, Louise Vinther Grøn, Maria Florencia Bambace, Jacopo Catalano, Jo Philips","doi":"10.1002/bit.28904","DOIUrl":"https://doi.org/10.1002/bit.28904","url":null,"abstract":"Acetogenic bacteria play an important role in various biotechnological processes, because of their chemolithoautotrophic metabolism converting carbon dioxide with molecular hydrogen (H<jats:sub>2</jats:sub>) as electron donor into acetate. As the main factor limiting acetogenesis is often H<jats:sub>2</jats:sub>, insights into the H<jats:sub>2</jats:sub> consumption kinetics of acetogens are required to assess their potential in biotechnological processes. In this study, initial H<jats:sub>2</jats:sub> consumption rates at a range of different initial H<jats:sub>2</jats:sub> concentrations were measured for three different acetogens. Interestingly, for all three strains, H<jats:sub>2</jats:sub> consumption was found to follow first‐order kinetics, i.e. the H<jats:sub>2</jats:sub> consumption rate increased linearly with the dissolved H<jats:sub>2</jats:sub> concentration, up to almost saturated H<jats:sub>2</jats:sub> levels (600 µM). This is in contrast with Monod kinetics and low half‐saturation concentrations, which have commonly been assumed for acetogens. The obtained biomass specific first‐order rate coefficients (<jats:italic>k</jats:italic><jats:sub>1</jats:sub><jats:sup>X</jats:sup>) were further validated by comparison with values obtained by fitting first‐order kinetics on previous time‐course experimental results. The latter method was also used to determine the <jats:italic>k</jats:italic><jats:sub>1</jats:sub><jats:sup>X</jats:sup> value of five additional acetogens strains. Biomass specific first‐order rate coefficients were found to vary up to six‐fold, with the highest <jats:italic>k</jats:italic><jats:sub>1</jats:sub><jats:sup>X</jats:sup> for <jats:italic>Acetobacterium wieringae</jats:italic> and the lowest for <jats:italic>Sporomusa sphaeroides</jats:italic>. Overall, our results demonstrate the importance of the dissolved H<jats:sub>2</jats:sub> concentration to understand the rate of acetogenesis in biotechnological systems.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"48 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887942","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}

{"title":"Dual‐Stage Cross‐Flow Filtration: Integrated Capture and Purification of Virus‐Like Particles","authors":"Annabelle Dietrich, Luca Heim, Jürgen Hubbuch","doi":"10.1002/bit.28914","DOIUrl":"https://doi.org/10.1002/bit.28914","url":null,"abstract":"Virus‐like particles (VLPs) are a versatile technology for the targeted delivery of genetic material through packaging and potential surface modifications for directed delivery or immunological issues. Although VLP production is relatively simple as they can be recombinantly produced using microorganisms such as <jats:italic>Escherichia coli</jats:italic>, their current downstream processing often relies on individually developed purification strategies. Integrating size‐selective separation techniques may allow standardized platform processing across VLP purification. This study presents an innovative dual‐stage cross‐flow filtration (CFF) set‐up for integrated capture and purification of VLPs, enabling processing solely based on the size‐selective separation techniques precipitation and filtration. The 2 μm/300 kDa MWCO membrane configuration allows the seamless integration of selective VLP precipitation, two consecutive diafiltration steps–first, for washing the VLP precipitates in the first membrane stage, and second, for isolating the re‐dissolved VLPs by continuously removing precipitant and contaminants in the second membrane stage–and ultrafiltration for setting a target VLP concentration. Compared to a single‐stage CFF set‐up, this dual‐stage CFF set‐up with its integrative, automated design demonstrated the capabilities of product accumulation and contaminant handling while maintaining high productivity. Overall, this study represents a significant advancement toward standardized platform processing of protein nanoparticles through precipitation and filtration, and underscores the potential to expand its applicability to diverse biological molecules, unique process conditions, other phase behavior‐dependent processes, and continuous processing.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"54 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887046","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}

{"title":"Recent Research on Chondrocyte Dedifferentiation and Insights for Regenerative Medicine","authors":"Weixian Su, Yupeng Nie, Shicong Zheng, Yongchang Yao","doi":"10.1002/bit.28915","DOIUrl":"https://doi.org/10.1002/bit.28915","url":null,"abstract":"Chondrocytes maintain the balance of the extracellular matrix by synthesizing glycoproteins, collagen, proteoglycans and hyaluronic acid. Chondrocyte dedifferentiation refers to a process in which chondrocytes lose their mature differentiated phenotype and transform into a fibroblast-like morphology with fewer differentiated stages and inferior function under external stimulation. The important mechanism of homeostasis loss in osteoarthritis (OA) is a change in the chondrocyte phenotype. The dedifferentiation markers of chondrocytes are upregulated in OA, and the pathogenic factors related to OA have also been shown to enhance chondrocyte dedifferentiation. In this review, we compile recent studies on chondrocyte dedifferentiation, with an emphasis on potential markers and the underlying mechanisms of dedifferentiation, as well as the current research progress in inhibiting dedifferentiation or achieving redifferentiation. A deep understanding of chondrocyte dedifferentiation would not only support the pathogenesis of OA theoretically but also provide insightful ideas for regenerative medicine to manipulate the functional phenotype of cells.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"11 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880111","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}

{"title":"Open-Source Anaerobic Digestion Modeling Platform, Anaerobic Digestion Model No. 1 Fast (ADM1F)","authors":"Kuang Zhu, Wenjuan Zhang, Elchin Jafarov, Satish Karra, Kurt Solander, Meltem Urgun Demirtas, Lutgarde Raskin, Steven Skerlos","doi":"10.1002/bit.28906","DOIUrl":"https://doi.org/10.1002/bit.28906","url":null,"abstract":"An open-source modeling platform, called Anaerobic Digestion Model No. 1 Fast (ADM1F), is introduced to achieve fast and numerically stable simulations of anaerobic digestion processes. ADM1F is compatible with an iPython interface to facilitate model configuration, simulation, data analysis, and visualization. Faster simulations and more stable results are accomplished by implementing an advanced open-source library of numerical methods called Portable Extensive Toolkit for Scientific Computation (PETSc) to solve the ADM1 system of equations. Leveraging PETSc, ADM1F can consistently complete a steady-state simulation under 0.2 s, over 99% faster than a benchmark ADM1 model implemented with MATLAB while achieving agreement of model outputs within 1% of those obtained with the benchmark model. For dynamic simulations, however, ADM1F has a computational speed advantage only when the influent characteristics update more frequently than every 4 h. The ability of ADM1F to be useful as a tool to study anaerobic digestion systems is demonstrated through two example implementations of ADM1F: (1) a two-phase co-digestion scenario evaluating the impact of the organic loading rate and the substrate composition on reactor performance and stability, and (2) a conventional digester scenario assessing the effectiveness of recovery strategies after disruptions that led to instability. These examples demonstrate how the high simulation speed and the convenience of the iPython interface allow ADM1F to complete complex analyses within minutes, much faster than computational strategies currently reported in the literature.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"89 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880237","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}