Biotechnology and Bioengineering最新文献_第8页

Expression of Viral DNA Polymerase in Synthetic Recombinant Adeno-Associated Virus Producer Cell Line Enhances Full Particle Productivity 在合成重组腺相关病毒生产细胞系中表达病毒 DNA 聚合酶可提高全粒子生产率

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-22 DOI: 10.1002/bit.28885

Yu-Chieh Lin, Han-Jung Kuo, Min Lu, Carissa Rungkittikhun, Wei-Shou Hu

{"title":"Expression of Viral DNA Polymerase in Synthetic Recombinant Adeno-Associated Virus Producer Cell Line Enhances Full Particle Productivity","authors":"Yu-Chieh Lin, Han-Jung Kuo, Min Lu, Carissa Rungkittikhun, Wei-Shou Hu","doi":"10.1002/bit.28885","DOIUrl":"10.1002/bit.28885","url":null,"abstract":"Recombinant adeno-associated virus (rAAV) is a widely used viral vector in gene therapy. To meet the growing clinical demand, a scalable production technology which can efficiently produce high-quality products is required. We have developed a synthetic biology strategy to generate HEK293-based cell lines which have integrated essential AAV and adenoviral helper genes and are capable of producing rAAV upon induction. One such cell line, GX6B, produced up to 106 capsids per cell, but only a much lower level of rAAV genomes. The low AAV genome titer limited its rAAV productivity and increased empty viral particle content. To boost AAV genome amplification, the coding sequence of the DNA polymerase complex (UL30/UL42) from helper Herpes Simplex Virus type 1 (HSV-1) was placed under an inducible promoter control and integrated into GX6B genome at a relatively low level. The resulting clones produced significantly higher titer of viral genomes, while their capsid level was unaffected. As a result, the encapsidated rAAV2 titer and the full particle content were significantly increased. We further demonstrated that this strategy of expressing HSV-1 DNA polymerase to increase full particle productivity could be implemented in a synthetic cell line producing another serotype rAAV8.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"424-434"},"PeriodicalIF":3.5,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28885","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Streamlined Clarification and Capture Process for Monoclonal Antibodies Using Fluidized Bed Centrifugation and Multi-Column Chromatography With Membrane Adsorbers 使用流化床离心法和带膜吸附器的多柱色谱法简化单克隆抗体的澄清和捕获过程。

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-18 DOI: 10.1002/bit.28884

Fabian Schmitz, Martin Saballus, Thomas Kruse, Mirjana Minceva, Markus Kampmann

{"title":"Streamlined Clarification and Capture Process for Monoclonal Antibodies Using Fluidized Bed Centrifugation and Multi-Column Chromatography With Membrane Adsorbers","authors":"Fabian Schmitz, Martin Saballus, Thomas Kruse, Mirjana Minceva, Markus Kampmann","doi":"10.1002/bit.28884","DOIUrl":"10.1002/bit.28884","url":null,"abstract":"Harmonizing unit operations in the downstream process of monoclonal antibodies (mAbs) has a high potential to overcome throughput limitations and reduce manufacturing costs. This study proposes a streamlined clarification and capture (S-CC) process concept for the continuous processing of cell broth harvested from a connected bioreactor. The process was realized with a fluidized bed centrifuge connected to depth and sterile filters, a surge tank, and a multi-column chromatography (MCC) unit. The MCC unit was operated in the rapid cycling simulated moving bed (RC-BioSMB) mode with five convective diffusive membrane adsorbers (MAs). A control strategy and the surge tank were used to adjust the loading flow rate of the MCC unit. The mAb was recovered with a total process yield of 90%, with high removal of the process-related impurities HCP (2.1 LRV) and DNA (2.9 LRV). Moreover, the S-CC process productivity of 4.2 g h−1 was up to 5.3 times higher than for comparable, hypothetical batch MA processes. In addition, the buffer consumption of the capture step could be reduced from 2.0 L g−1 in batch mode to 1.2 L g−1 in the RC-BioSMB mode. These results demonstrate the high potential of streamlined interconnected unit operations to improve the overall mAb downstream process performance.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"382-394"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regeneration of Spent Culture Media for Sustainable and Continuous mAb Production via Ion Concentration Polarization 通过离子浓度极化再生废培养基，实现可持续和连续的 mAb 生产。

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-18 DOI: 10.1002/bit.28888

Eric Wynne, Junghyo Yoon, Dohyun Park, Mingyang Cui, Caitlin Morris, Jaeweon Lee, Zhao Wang, Seongkyu Yoon, Jongyoon Han

{"title":"Regeneration of Spent Culture Media for Sustainable and Continuous mAb Production via Ion Concentration Polarization","authors":"Eric Wynne, Junghyo Yoon, Dohyun Park, Mingyang Cui, Caitlin Morris, Jaeweon Lee, Zhao Wang, Seongkyu Yoon, Jongyoon Han","doi":"10.1002/bit.28888","DOIUrl":"10.1002/bit.28888","url":null,"abstract":"In modern bioprocessing, cell culture media is one of the most significant cost drivers, yet the nutrients and other critical factors in the media are often not fully utilized. With the renewed emphasis on reducing the cost of bioprocessing, there is much interest in reducing the overall use of cell culture media. In this work, we introduce a mesoscale microfluidic separation device based on the ion concentration polarization (ICP) process to regenerate the spent media for reuse by removing critical waste products from the cell culture that are known to inhibit the growth of the cells. We demonstrated that up to 75% of spent culture media can be regenerated and reused without affecting the cell viability. A detailed analysis of the materials consumed during antibody production indicated that one could improve the water process mass intensity by up to 33% by regenerating and recycling the media. Given that ICP separation systems have already been scaled up to support large-volume processing, it would be feasible to deploy this technology for manufacturing scale bioreactors (e.g., 50 L perfusion culture of CHO cells), reducing the overall operation cost and water use.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"373-381"},"PeriodicalIF":3.5,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adaptation of Aglycosylated Monoclonal Antibodies for Improved Production in Komagataella phaffii 适应 Aglycosylated 单克隆抗体以改进 Komagataella phaffii 的生产。

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-14 DOI: 10.1002/bit.28878

Yuchen Yang, Neil C. Dalvie, Joseph R. Brady, Christopher A. Naranjo, Timothy Lorgeree, Sergio A. Rodriguez-Aponte, Ryan S. Johnston, Mary K. Tracey, Carmen M. Elenberger, Eric Lee, Mark Tié, Kerry R. Love, J. Christopher Love

{"title":"Adaptation of Aglycosylated Monoclonal Antibodies for Improved Production in Komagataella phaffii","authors":"Yuchen Yang, Neil C. Dalvie, Joseph R. Brady, Christopher A. Naranjo, Timothy Lorgeree, Sergio A. Rodriguez-Aponte, Ryan S. Johnston, Mary K. Tracey, Carmen M. Elenberger, Eric Lee, Mark Tié, Kerry R. Love, J. Christopher Love","doi":"10.1002/bit.28878","DOIUrl":"10.1002/bit.28878","url":null,"abstract":"Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals manufactured by well-established processes using Chinese Hamster Ovary (CHO) cells. Next-generation biomanufacturing using alternative hosts like Komagataella phaffii could improve the accessibility of these medicines, address broad societal goals for sustainability, and offer financial advantages for accelerated development of new products. Antibodies produced by K. phaffii, however, may manifest unique molecular quality attributes, like host-dependent, product-related variants, that could raise potential concerns for clinical use. We demonstrate here conservative modifications to the amino acid sequence of aglycosylated antibodies based on the human IgG1 isotype that minimize product-related variations when secreted by K. phaffii. A combination of 2–3 changes of amino acids reduced variations across six different aglycosylated versions of commercial mAbs. Expression of a modified sequence of NIST mAb in both K. phaffii and CHO cells showed comparable biophysical properties and molecular variations. These results suggest a path toward the production of high-quality mAbs that could be expressed interchangeably by either yeast or mammalian cells. Improving molecular designs of proteins to enable a range of manufacturing strategies for well-characterized biopharmaceuticals could accelerate global accessibility and innovations.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"361-372"},"PeriodicalIF":3.5,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Perfusion Process Intensification for Lentivirus Production Using a Novel Scale-Down Model 利用新型缩小模型强化慢病毒生产的灌注过程

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-13 DOI: 10.1002/bit.28880

Maximilian Klimpel, Beatrice Pflüger-Müller, Marta Arrizabalaga Cascallana, Sarah Schwingal, Nikki Indresh Lal, Thomas Noll, Vicky Pirzas, Holger Laux

{"title":"Perfusion Process Intensification for Lentivirus Production Using a Novel Scale-Down Model","authors":"Maximilian Klimpel, Beatrice Pflüger-Müller, Marta Arrizabalaga Cascallana, Sarah Schwingal, Nikki Indresh Lal, Thomas Noll, Vicky Pirzas, Holger Laux","doi":"10.1002/bit.28880","DOIUrl":"10.1002/bit.28880","url":null,"abstract":"Process intensification has become an important strategy to lower production costs and increase manufacturing capacities for biopharmaceutical products. In particular for the production of viral vectors like lentiviruses (LVs), the transition from (fed-)batch to perfusion processes is a key strategy to meet the increasing demands for cell and gene therapy applications. However, perfusion processes are associated with higher medium consumption. Therefore, it is necessary to develop appropriate small-scale models to reduce development costs. In this work, we present the use of the acoustic wave separation technology in combination with the Ambr 250 high throughput bioreactor system for intensified perfusion process development using stable LV producer cells. The intensified perfusion process developed in the Ambr 250 model, performed at a harvest rate of 3 vessel volumes per day (VVD) and high cell densities, resulted in a 1.4-fold higher cell-specific functional virus yield and 2.8-fold higher volumetric virus yield compared to the control process at a harvest rate of 1 VVD. The findings were verified at bench scale after optimizing the bioreactor set-up, resulting in a 1.4-fold higher cell-specific functional virus yield and 3.1-fold higher volumetric virus yield.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"344-360"},"PeriodicalIF":3.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28880","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biotechnology and Bioengineering: Volume 121, Number 12, December 2024 生物技术与生物工程第 121 卷第 12 号，2024 年 12 月

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-11 DOI: 10.1002/bit.28887

引用次数: 0

Correction to “A High-Throughput Expression and Screening Platform for Applications-Driven PETase Engineering” 对 "应用驱动 PETase 工程的高通量表达和筛选平台 "的更正

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-11 DOI: 10.1002/bit.28882

{"title":"Correction to “A High-Throughput Expression and Screening Platform for Applications-Driven PETase Engineering”","authors":"","doi":"10.1002/bit.28882","DOIUrl":"10.1002/bit.28882","url":null,"abstract":"Zurier, H. S., & Goddard, J. M. (2023). A High-Throughput Expression and Screening Platform for Applications-Driven PETase Engineering. Biotechnology and Bioengineering 120, 1000–1014. https://doi.org/10.1002/bit.28319In the originally published article, one of the references was cited incorrectly. The incorrect reference is:Ebersbach, H., Geisse, S., Vincent, K. J., Zurini, M., McNeely, P. M., Naranjo, A. N., Robinson, A. S., Lingg, N., Zhang, P., Song, Z., Bardor, M., Van Beers, M. M. C., Kallberg, K., Johansson, H.-O., Bulow, L., Godawat, R., Brower, K., Jain, S., Konstantinov, K., … Mandenius, C.-F. (2012). A High-Throughput Assay for Enzymatic Polyester Hydrolysis Activity by Fluorimetric Detection. Biotechnology Journal, 7, 1517–1521.The correct reference is:Wei, R., Oeser, T., Billig, S., & Zimmermann, W. (2012). A High-Throughput Assay for Enzymatic Polyester Hydrolysis Activity by Fluorimetric Detection. Biotechnology Journal, 7, no. 12, 1517–1521. doi:10.1002/biot.201200119. Epub 2012 Jun 27.We apologize for this error.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"252"},"PeriodicalIF":3.5,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bit.28882","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mathematical Modeling and Simulation of 1,3-Propanediol Production by Klebsiella pneumoniae BLh-1 in a Batch Bioreactor Using Bayesian Statistics 利用贝叶斯统计对批式生物反应器中肺炎克雷伯氏菌 BLh-1 生产 1,3-丙二醇的过程进行数学建模和模拟

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-08 DOI: 10.1002/bit.28883

Nathalia Lobato Moraes, Mailson Batista de Vilhena, Daniele Misturini Rossi, Bruno Marques Viegas

{"title":"Mathematical Modeling and Simulation of 1,3-Propanediol Production by Klebsiella pneumoniae BLh-1 in a Batch Bioreactor Using Bayesian Statistics","authors":"Nathalia Lobato Moraes, Mailson Batista de Vilhena, Daniele Misturini Rossi, Bruno Marques Viegas","doi":"10.1002/bit.28883","DOIUrl":"10.1002/bit.28883","url":null,"abstract":"<div>\u0000 \u0000 Mathematical modeling and computer simulation are fundamental for optimizing biotechnological processes, enabling cost reduction and scalability, thereby driving advancements in the bioindustry. In this work, mathematical modeling and estimation of fermentative kinetic parameters were carried out to produce 1,3-propanediol (1,3-PDO) from residual glycerol and Klebsiella pneumoniae BLh-1. The Markov chain Monte Carlo method, using the Metropolis-Hastings algorithm, was applied to experimental data from a batch bioreactor under aerobic and anaerobic conditions. Sensitivity analysis and parameter evolution studies were conducted. The root-mean-square error (rRMSE) was chosen as the validation and calibration metric for the developed mathematical model. The results indicated that the average tolerance of glycerol was 174.68 and 44.85 g L−1, the inhibitory products was 150.95 g L−1 for ethanol and 35.56 g L−1 for 1,3-PDO, and the maximum specific rate of cell growth was 0.189 and 0.275 h−1, for aerobic and anaerobic cultures, respectively. The model presented excellent fits in both crops, with rRMSE values between 0.09 − 33.74% and 3.58 − 31.82%, for the aerobic and anaerobic environment, respectively. With this, it was possible to evaluate and extract relevant information for a better understanding and control of the bioprocess.</div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"333-343"},"PeriodicalIF":3.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597611","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

Implementation of Innovative Process Analytical Technologies to Characterize Critical Quality Attributes of Co-Formulated Monoclonal Antibody Products 采用创新工艺分析技术表征共配单克隆抗体产品的关键质量属性

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-07 DOI: 10.1002/bit.28881

Apurva Godbole, Lyufei Chen, Jay Desai, Smita Raghava, Richard Ruzanski, Bhumit Patel, Emmanuel Appiah-Amponsah, Hanzhou Feng

{"title":"Implementation of Innovative Process Analytical Technologies to Characterize Critical Quality Attributes of Co-Formulated Monoclonal Antibody Products","authors":"Apurva Godbole, Lyufei Chen, Jay Desai, Smita Raghava, Richard Ruzanski, Bhumit Patel, Emmanuel Appiah-Amponsah, Hanzhou Feng","doi":"10.1002/bit.28881","DOIUrl":"10.1002/bit.28881","url":null,"abstract":"<div>\u0000 \u0000 Characterizing co-formulated monoclonal antibodies (mAbs) poses significant challenges in the pharmaceutical industry. Due to the high structural similarity of the mAbs, traditional analytical methods, compounded by the lengthy method development process, hinder product development and manufacturing efficiency. There is increasing critical need in the pharmaceutical industry to streamline analytical approaches, minimizing time and resources, ensuring a rapid clinical entry and cost-effective manufacturing. This study investigates the application of process analytical technologies (PAT) to address such challenges. Our investigation introduces two complementary technologies, on-line ultra-performance liquid chromatography (online UPLC) and multimode fluorescence spectroscopy (MMFS), as potential PAT tools tailored for characterizing critical quality attributes (CQA) in co-formulated mAb products. Specifically, the CQAs under evaluation include the total protein concentration of the mAbs within the co-formulation and the ratio of mAb A to mAb B. Online UPLC enables direct and automated measurement of the CQAs through physical separation, while MMFS determines them in a non-destructive and more swift manner based on chemometric modeling. We demonstrate these technologies' comparable performance to conventional methods, alongside substantial benefits such as reduced analytical turnaround time and decreased laboratory efforts. Ultimately, integrating them as innovative PAT tools expedites the delivery of therapeutic solutions to patients and enhances manufacturing efficiency, aligning with the imperative for swift translation of scientific discoveries into clinical benefits.</div>","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"322-332"},"PeriodicalIF":3.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142597612","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

Metabolic Engineering of Nonmodel Yeast Issatchenkia orientalis SD108 for 5-Aminolevulinic Acid Production 生产 5-氨基乙酰丙酸的非模式酵母 Issatchenkia orientalis SD108 的代谢工程。

IF 3.5 2区生物学

Biotechnology and Bioengineering Pub Date : 2024-11-06 DOI: 10.1002/bit.28877

Shih-I Tan, I-Son Ng, Huimin Zhao

{"title":"Metabolic Engineering of Nonmodel Yeast Issatchenkia orientalis SD108 for 5-Aminolevulinic Acid Production","authors":"Shih-I Tan, I-Son Ng, Huimin Zhao","doi":"10.1002/bit.28877","DOIUrl":"10.1002/bit.28877","url":null,"abstract":"Biological production of 5-aminolevulinic acid (5-ALA) has received growing attention over the years. However, there is the tradeoff between 5-ALA biosynthesis and cell growth because the fermentation broth will become acidic due to the production of 5-ALA. To address this limitation, we engineered an acid-tolerant yeast, Issatchenkia orientalis SD108, for 5-ALA production. We first discovered that the cell growth rate of I. orientalis SD108 was boosted by 5-ALA and its endogenous ALA synthetase (ALAS) showed higher activity than those homologs from other yeasts. The titer of 5-ALA was improved from 28 mg/L to 120-, 150-, and 300 mg/L, by optimizing plasmid design, overexpressing a transporter, and increasing gene copy number, respectively. After redirecting the metabolic flux using the pyruvate decarboxylase (PDC) knockout strain (SD108ΔPDC) and culturing with urea, we increased the titer of 5-ALA to 510 mg/L, a 13-fold enhancement, proving the importance of the newly identified IoALAS with higher activity and the strategic selection of nitrogen sources for knockout strains. This study demonstrates the acid-tolerant I. orientalis SD108ΔPDC has a high potential for 5-ALA production at a large scale in the future.","PeriodicalId":9168,"journal":{"name":"Biotechnology and Bioengineering","volume":"122 2","pages":"415-423"},"PeriodicalIF":3.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0