Biotechnology and Bioengineering最新文献

CS/Gel/MWCNTs Conductive Scaffolds Assisted by Electrical Stimulus for Skin Tissue Engineering. 电刺激辅助CS/凝胶/MWCNTs导电支架在皮肤组织工程中的应用

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-15 DOI: 10.1002/bit.29025

Zixian Liu,Zijun Ma,Nini Li,Jinyao Zhang,Meng Li,Lu Han,Rong Cheng,Zhizhong Shen,Dan Han,Shengbo Sang

引用次数: 0

Modeling and Optimization of Recombinant Tocilizumab Production From Pichia pastoris Using Response Surface Methodology and Artificial Neural Network. 基于响应面法和人工神经网络的毕赤酵母重组Tocilizumab生产建模与优化。

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-15 DOI: 10.1002/bit.29024

Prabir Kumar Das,Ansuman Sahoo,Venkata Dasu Veeranki

{"title":"Modeling and Optimization of Recombinant Tocilizumab Production From Pichia pastoris Using Response Surface Methodology and Artificial Neural Network.","authors":"Prabir Kumar Das,Ansuman Sahoo,Venkata Dasu Veeranki","doi":"10.1002/bit.29024","DOIUrl":"https://doi.org/10.1002/bit.29024","url":null,"abstract":"This study has demonstrated the optimization of the defined medium that significantly enhanced the production of recombinant monoclonal antibody (mAb) Tocilizumab (TCZ) as full-length and Fab fragment from Pichia pastoris. Out of the four tested defined media, FM22 was found to be suitable for the growth of recombinant strains and antibody yield. Among the various carbon and nitrogen sources tested, mannitol and glycine, respectively, were found to be suitable for the enhanced production of full-length TCZ. Similarly, sorbitol and ammonium sulfate were found to be suitable carbon and nitrogen sources, respectively, for enhanced production of Fab. The medium components that significantly influenced the production of TCZ were found to be mannitol, glycine, histidine, and K2SO4 and sorbitol, ammonium sulfate, KH2PO4, and CaSO4.2H2O for full-length and Fab, respectively, using a two-level factorial Plackett-Burman design. The screened medium components were optimized using response surface methodology (Box-Behnken Design). Artificial neural network (ANN) models combined with genetic algorithms (GA) further improved predictions and showed a remarkable impact on mAb production in P. pastoris. Under the optimal levels of medium components, the full-length TCZ and Fab were determined to be 0.35 mg/L and 0.42 g/L, respectively, in the shake-flask culture. The yield of full-length TCZ and Fab in batch reactor (2-L culture) was found to be 0.44 mg/L and 0.45 g/L, respectively, at the optimal levels of the medium components. The overall increased yields were observed to be 3.8 and 2.9-folds of full-length TCZ and Fab, respectively.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"23 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992096","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

CRISPR-Editing of the Vero Cell Line Improves Processability of Live Virus Vaccines by Enabling Targeted Proteolysis of Fibronectin. crispr编辑的Vero细胞系通过激活纤维连接蛋白的靶向蛋白水解提高了活病毒疫苗的加工能力。

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-14 DOI: 10.1002/bit.29028

Jackson K B Cahn,Henry Ludwicki,Jillian Shingler,Shannon Gulvin,Young Zhang,Adam Kristopeit,Christopher Ton,Michael A Winters,James M Wagner,Jeffrey Moore

引用次数: 0

Developing a Model for Virus Contamination in Perfusion Bioreactors to Establish Rational Control Strategies for Integrated Continuous Bioprocessing. 建立灌注式生物反应器中病毒污染模型，建立集成连续生物处理的合理控制策略。

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-13 DOI: 10.1002/bit.29021

Takao Ito,Takashi Nihei,Koichi Yamamoto,Naoto Watanabe,Yoshiyuki Tokieda,Yumiko Masuda,Masaki Okada

{"title":"Developing a Model for Virus Contamination in Perfusion Bioreactors to Establish Rational Control Strategies for Integrated Continuous Bioprocessing.","authors":"Takao Ito,Takashi Nihei,Koichi Yamamoto,Naoto Watanabe,Yoshiyuki Tokieda,Yumiko Masuda,Masaki Okada","doi":"10.1002/bit.29021","DOIUrl":"https://doi.org/10.1002/bit.29021","url":null,"abstract":"A viral contamination model for steady-state perfusion cell culture was developed to assess how sampling frequency and volume impacted the expected downstream viral clearance factor in integrated continuous biomanufacturing processes. The model used population balance rate equations for cells and free virions, incorporating the virus infection cycle. It simulated the states of cell cultures for both endogenous viruses, which are potentially present within the cells and can be released from them, and adventitious viruses after contamination. The model also reproduced differences in virus concentration between bioreactors and harvests caused by sieving through the cell retention device. For virus risk assessments in integrated continuous biomanufacturing, the model evaluated the probability of detecting contamination based on the volume fraction of the sample tested and the downstream viral transmission by number of days after contamination. Considering the infection scenario with mouse minute virus (MVM) in 100 × 106 cells/mL cell culture for adventitious virus contamination, a notable decline in viable cell density was observed starting from Day 4. To ensure 99.999% safety of final products, the total downstream clearance achieving a log reduction value (LRV) > 15 LRV is required to remove the increased virus. If daily sampling is conducted and a downstream clearance is planned to satisfy the removal of potentially undetected MVM, a total clearance of 9 LRV is sufficient. This model enables us to simulate different scenarios for viral contamination and has the advantage of allowing assessments of virus safety strategies.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"145 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945547","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

Biotechnology and Bioengineering: Volume 122, Number 6, June 2025 生物技术和生物工程：第122卷，第6号，2025年6月

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-12 DOI: 10.1002/bit.28746

引用次数: 0

Protein Engineering for Enhancing Electron Transfer in P450‐Mediated Catalysis 增强P450介导催化中电子转移的蛋白质工程

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-09 DOI: 10.1002/bit.29023

Yuemin Li, Hongwei Yu, Lidan Ye

{"title":"Protein Engineering for Enhancing Electron Transfer in P450‐Mediated Catalysis","authors":"Yuemin Li, Hongwei Yu, Lidan Ye","doi":"10.1002/bit.29023","DOIUrl":"https://doi.org/10.1002/bit.29023","url":null,"abstract":"Cytochrome P450 enzymes (P450s) are versatile biocatalysts with applications spanning pharmaceutical development and natural product biosynthesis. A critical bottleneck in P450‐mediated reactions is the electron transfer process, which often limits catalytic efficiency and promotes uncoupling events leading to reactive oxygen species (ROS) formation. This review comprehensively examines recent protein engineering strategies aimed at enhancing electron transfer efficiency in P450 systems. We explore the design and application of different fusion constructs, which improve proximity between the P450 enzyme and its redox partners (RPs), as well as scaffold‐mediated protein assembly, enabling precise spatial organization of P450s and RPs. Furthermore, we discuss targeted modifications at the P450‐RP interaction interface and optimization of electron transfer pathways through site‐directed mutagenesis and directed evolution. These strategies enhance catalytic activity, improve coupling efficiency, and reduce ROS formation. Finally, we address the remaining challenges in understanding and engineering P450 electron transfer, and discuss the future directions, emphasizing the need for advanced computational modeling, structural characterization, and integration of synthetic and systems biology approaches.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"141 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926905","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

Hybrid Modeling of the Reversed‐Phase Chromatographic Purification of an Oligonucleotide: Few‐Shot Learning From Differentiable Physics Solver‐in‐the‐Loop 反相色谱纯化寡核苷酸的混合建模：从可微分物理求解器中学习

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-09 DOI: 10.1002/bit.29018

Yu‐Cheng Chen, Ismaele Fioretti, Dong‐Qiang Lin, Mattia Sponchioni

{"title":"Hybrid Modeling of the Reversed‐Phase Chromatographic Purification of an Oligonucleotide: Few‐Shot Learning From Differentiable Physics Solver‐in‐the‐Loop","authors":"Yu‐Cheng Chen, Ismaele Fioretti, Dong‐Qiang Lin, Mattia Sponchioni","doi":"10.1002/bit.29018","DOIUrl":"https://doi.org/10.1002/bit.29018","url":null,"abstract":"Hybrid models integrate mechanistic and data‐driven components, effectively addressing the challenges of limited process understanding and data availability typical of biopharmaceutical processes. In this study, we applied a hybrid modeling framework named differentiable physics solver‐in‐the‐loop (DP‐SOL) to describe the reversed‐phase chromatographic purification of an oligonucleotide, overcoming the mentioned limitations of purely mechanistic and data‐driven models. The framework establishes a connection between neural networks (NNs) and mechanistic models through differentiable physical operators and their gradients. We first collected a data set comprising six linear gradient elution experiments at different resin loadings and gradient slopes, split in three experiments each for training and testing, for few‐shot learning. The hyperparameters were determined through a grid search, resulting in a NN with two hidden layers and 14 nodes. Compared to a calibrated mechanistic model used for initialization of NN, the DP‐SOL hybrid model showed significant performance improvement on both training and testing sets, with 0.97 for the former. The good predictivity of DP‐SOL is attributed to the combination of mechanistic models and NNs at the solver level. As a novel and versatile hybrid modeling paradigm, DP‐SOL has the potential to significantly impact modeling approaches in the downstream processing field and the broader biopharmaceutical sector.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"44 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143930736","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

RSEA: A Web Server for Pathway Enrichment Analysis of Metabolic Reaction Sets RSEA：用于代谢反应集途径富集分析的Web服务器

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-09 DOI: 10.1002/bit.29020

Merve Yarıcı, Furkan Cantürk, Serdar Dursun, Hatice Nur Aydın, Muhammed Erkan Karabekmez

{"title":"RSEA: A Web Server for Pathway Enrichment Analysis of Metabolic Reaction Sets","authors":"Merve Yarıcı, Furkan Cantürk, Serdar Dursun, Hatice Nur Aydın, Muhammed Erkan Karabekmez","doi":"10.1002/bit.29020","DOIUrl":"https://doi.org/10.1002/bit.29020","url":null,"abstract":"Changes in biological pathways provide essential clues about metabolism. Genome-scale metabolic models (GEM) are network-based templates that computationally describe all stoichiometric associations and gene-protein reaction (GPR) relations found in an organism for all its metabolic genes and metabolites. Using reaction stoichiometry as input, GEMs mathematically simulate metabolic reaction fluxes occurring in an organism and predict changes in the metabolic system under the relevant condition. Multiple tools and approaches in the literature can capture fluxes sensitive to a given condition by using GEMs. However, functional enrichment analysis of these reaction lists in a systems biology perspective is not straightforward. Here, we introduce RSEA to annotate given reaction sets to significantly related metabolic pathways: Reaction Set Enrichment Analysis web server tool. RSEA converts given reaction list derived from GEMs into proper reaction identifiers and statistically analyze its enrichment in metabolic pathways. RSEA is designed to provide researchers with a practical and user-friendly platform to explore and interpret sets of reactions in biological pathways and freely available online (https://rseatool.com/).","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"39 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926912","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

A Genetic Algorithms-Based Neural Network Model to Monitor Gibberellic Acid GA3 Fermentation Process by Fusarium fujikuroi 基于遗传算法的神经网络模型监测赤霉病菌GA3发酵过程

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-08 DOI: 10.1002/bit.29022

Jia-Cong Huang, Jun-Lin Wu, Zhi-Kui Nie, Tian-Qiong Shi

{"title":"A Genetic Algorithms-Based Neural Network Model to Monitor Gibberellic Acid GA3 Fermentation Process by Fusarium fujikuroi","authors":"Jia-Cong Huang, Jun-Lin Wu, Zhi-Kui Nie, Tian-Qiong Shi","doi":"10.1002/bit.29022","DOIUrl":"https://doi.org/10.1002/bit.29022","url":null,"abstract":"A genetic algorithm-optimized neural network (ANN-GA) was developed for real-time monitoring of gibberellin (GA3) production during <i>Fusarium fujikuroi</i> fermentation. This model addresses the limitations of traditional off-line detection methods, such as contamination risks and delayed feedback, by integrating six critical inputs—initial glucose concentration, fermentation time, temperature, pH, dissolved oxygen, and rotational speed—to predict glucose consumption and GA3 synthesis with an accuracy of 99.41%. During the implementation phase, by dynamically controlling the temperature (28°C–32°C) and pH, the biomass accumulation rate increased by 84% within 48 h, while the GA3 accumulation rate improved by 66.7% compared to constant-temperature fermentation at 28°C. The ANN-GA framework enables dynamic adjustment of glucose supply based on real-time predictions, thereby optimizing carbon source utilization and enhancing process stability. This data-driven approach effectively overcomes the drawbacks of costly sensors and labor-intensive manual sampling, showcasing significant potential for industrial-scale fermentation optimization. With its high accuracy and adaptability, the model holds substantial application value in advancing intelligent biological process control for secondary metabolite production.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"48 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926436","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

Isolation of Anammoxosomes From the Aggregate Culture of Ca. Brocadia Sapporoensis and Assembly of Ladderane Liposomes 札幌花楸聚集培养厌氨粘液体的分离及脂质体的组装

IF 3.8 2区生物学

Biotechnology and Bioengineering Pub Date : 2025-05-08 DOI: 10.1002/bit.29011

Tomáš Podzimek, Terezie Cisarová, Michal Dvořák, Barbora Vokatá, Christina Karmann, Jaroslav Hanuš, Martin Balouch, Matěj Malý, Jana Hajšlová, Vojtěch Kouba, Jan Bartáček, František Štěpánek, Petra Lipovová

{"title":"Isolation of Anammoxosomes From the Aggregate Culture of Ca. Brocadia Sapporoensis and Assembly of Ladderane Liposomes","authors":"Tomáš Podzimek, Terezie Cisarová, Michal Dvořák, Barbora Vokatá, Christina Karmann, Jaroslav Hanuš, Martin Balouch, Matěj Malý, Jana Hajšlová, Vojtěch Kouba, Jan Bartáček, František Štěpánek, Petra Lipovová","doi":"10.1002/bit.29011","DOIUrl":"https://doi.org/10.1002/bit.29011","url":null,"abstract":"Anammox bacteria wield an energy‐efficient nitrogen metabolism enveloped in anammoxosome organelle composed of unique ladderane lipids. Thus, waste anammox biomass seems to be an attractive target for the isolation of ladderanes and subsequent production of artificial vesicles for drug delivery. This study proposed a novel method to isolate ladderane‐rich anammoxosomes from aggregate mixed culture of Ca. Brocadia sapporoensis. Compared to conventional isolation protocols, the protocol was simplified by omitting the prepurification of anammox cells, replacing Percoll® with a sucrose gradient and prolonging the application of EDTA. This enhanced and simplified procedure efficiently removed EPS and other debris, thus yielding the layer of anammoxosomes as confirmed by control experiments and TEM. For the first time, the resulting ladderane isolates were used for the preparation of liposomes, both with and without the addition of pure dipalmitoylphosphatidylcholine (DPPC). Vesicles were successfully created, characterised by TEM and DLS, and anammox‐based ladderanes were incorporated into their walls. These liposomes had interesting functional properties such as increased colloid stability at elevated concentrations, meaning a reduced tendency to form aggregates compared to model liposomes made solely of DPPC. Overall, this study offers insights into converting waste anammox biomass into a valuable resource for drug delivery.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"35 1","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920046","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