Biotechnology Journal最新文献

A New Conditional Transcription Factor for Use in Toxoplasma Gondii. 一种新的用于刚地弓形虫的条件转录因子。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-05-01 DOI: 10.1002/biot.70240

Mohammad Farouq Sharifpour, Shadi Khadiv, Alessandro D Uboldi, Amalie A Jayawickrama, Sarah Manning, Jonathan Whittall, Cynthia D K Bottema, John T Ellis, Daniel K Howe, Danny W Wilson, Farhid Hemmatzadeh, Christopher J Tonkin, Milton M McAllister

{"title":"A New Conditional Transcription Factor for Use in Toxoplasma Gondii.","authors":"Mohammad Farouq Sharifpour, Shadi Khadiv, Alessandro D Uboldi, Amalie A Jayawickrama, Sarah Manning, Jonathan Whittall, Cynthia D K Bottema, John T Ellis, Daniel K Howe, Danny W Wilson, Farhid Hemmatzadeh, Christopher J Tonkin, Milton M McAllister","doi":"10.1002/biot.70240","DOIUrl":"10.1002/biot.70240","url":null,"abstract":"Toxoplasma gondii is an intracellular eukaryotic parasite in the phylum Apicomplexa. Reversible, conditional control of gene transcription was achieved previously in this organism using a tet-off system that was controlled by tetracycline. Although revolutionary for the field at the time, that system in Toxoplasma yielded modest signal-to-noise ratios (SNR) and proved to be leaky in the \"off\" state (i.e., it suffered from high background expression). Here we report the development of a new reversible and robust Conditional Transcription Factor (CTF) that is controlled by rapamycin. Although we originally intended to design a dimerizable drug-on transcription control system, the CTF unexpectedly functions in a drug-off fashion. In stably-transfected tachyzoites, CTF regulates a fluorescent reporter gene in Toxoplasma to achieve almost no background expression in the presence of rapamycin (i.e. near-zero leakiness), while in the absence of rapamycin 84% of tachyzoites express EYFP in comparison with 87% of constitutively-expressed positive controls, with 59% mean fluorescence intensity relative to positive controls. Conditional regulation of the median fluorescence intensity of the reporter gene reached an impressive SNR averaging 1489, approximating an \"on/off\" switch. The modular design of the CTF is expected to facilitate application to varied genes, incremental modifications, and adaptation for use in other apicomplexan organisms.","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 5","pages":"e70240"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13150947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Engineering Modification for the Efficient Synthesis of β-ionone by Yarrowia lipolytica. 脂质体耶氏菌高效合成β-离子酮的工程修饰。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-05-01 DOI: 10.1002/biot.70230

Kai Gu, Ping Lin, Guocheng Du, Jian Chen, Juan Zhang, Zheng Peng

{"title":"Engineering Modification for the Efficient Synthesis of β-ionone by Yarrowia lipolytica.","authors":"Kai Gu, Ping Lin, Guocheng Du, Jian Chen, Juan Zhang, Zheng Peng","doi":"10.1002/biot.70230","DOIUrl":"https://doi.org/10.1002/biot.70230","url":null,"abstract":"β-Ionone, prized for its characteristic violet aroma and woody undertones, has emerged as a valuable ingredient in the fragrance industry. Beyond its aromatic qualities, growing interest in its diverse biological activities has positioned it as a compound of relevance in the biopharmaceutical field. As production strategies shift from traditional chemical synthesis toward more sustainable biological routes, this study explores the engineered biosynthesis of β-ionone in Yarrowia lipolytica. Through systematic combinatorial metabolic engineering, a strain capable of accumulating 743 mg/L of β-carotene was constructed. Heterologous expression of the petunia-derived carotenoid cleavage dioxygenase gene PhCCD1 enabled efficient conversion of β-carotene to β-ionone, yielding 137 mg/L in shake-flask cultures. Subsequent integration of the isoprene alcohol metabolic pathway further enhanced precursor supply, boosting β-ionone production to 236.7 mg/L in shake flasks. In a 5 L bioreactor, optimization of the culture medium and feeding strategy led to a final titer of 624.7 mg/L. Collectively, these results establish a promising and replicable strategy for developing microbial cell factories capable of efficient β-ionone synthesis.","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 5","pages":"e70230"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Lactiplantibacillus plantarum Z6 Improves Functional Constipation in Infants. 植物乳杆菌Z6改善婴儿功能性便秘。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-05-01 DOI: 10.1002/biot.70233

Xiaoni Zhou, Gang Hu, Jingwu Wu, Yunfeng Duan, Bihui Zhu, Wen Deng, Yunfeng Shen, Xiaolin Wang, Shuhui Li, Jing Wei, Chunbo Zhang, Xuewei Lei, Tingtao Chen

{"title":"Lactiplantibacillus plantarum Z6 Improves Functional Constipation in Infants.","authors":"Xiaoni Zhou, Gang Hu, Jingwu Wu, Yunfeng Duan, Bihui Zhu, Wen Deng, Yunfeng Shen, Xiaolin Wang, Shuhui Li, Jing Wei, Chunbo Zhang, Xuewei Lei, Tingtao Chen","doi":"10.1002/biot.70233","DOIUrl":"https://doi.org/10.1002/biot.70233","url":null,"abstract":"Objective: To evaluate the efficacy and safety of Lactiplantibacillus plantarum Z6 (L. plantarum Z6) supplementation in infants with functional constipation (FC) and to explore its effects on gut microbiota composition.Study design: In this randomized, placebo-controlled trial, 100 infants diagnosed with FC were enrolled and allocated to receive either L. plantarum Z6 or placebo. Clinical outcomes, including weekly bowel movement frequency, Bristol stool scale scores, and Wexner constipation scores, were assessed. Serum 5-hydroxytryptamine (5-HT) levels and fecal microbiota profiles were analyzed to evaluate neurogastrointestinal and microbial responses.Results: L. plantarum Z6 supplementation significantly increased weekly bowel movements and Bristol stool scores while reducing Wexner scores (p < 0.05). Serum 5-HT concentrations were elevated, indicating improved gastrointestinal motility. Gut microbiota analysis revealed enhanced α-diversity, higher abundances of Bifidobacterium, Gemmiger, and Lactobacillus, and reduced Streptococcus. Correlation analysis demonstrated a positive association between L. plantarum Z6 intake and Bifidobacterium enrichment, suggesting targeted modulation of beneficial taxa.Conclusions: L. plantarum Z6 is a safe and effective probiotic intervention for infantile functional constipation. The results highlight its potential to improve bowel function and beneficially reshape the gut microbiota, offering a microbiota-targeted therapeutic strategy for pediatric gastrointestinal disorders. Chinese Clinical Trial Registry ID: ChiCTR2300073079.","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 5","pages":"e70233"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147808956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Production of (R)-1,3-butanediol via an Isozyme co-expression Strategy in Escherichia coli 通过同工酶共表达策略在大肠杆菌中产生(R)-1,3-丁二醇

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-04-08 DOI: 10.1002/biot.70224

Huifang Zhang, Dong Peng, Pinzhou Chen, Xiwei Peng, Mengting Li, Qingguo Liu, Yong Chen, Chenjie Zhu, Zhenyu Wang, Dong Liu, Hanjie Ying

{"title":"Production of (R)-1,3-butanediol via an Isozyme co-expression Strategy in Escherichia coli","authors":"Huifang Zhang, Dong Peng, Pinzhou Chen, Xiwei Peng, Mengting Li, Qingguo Liu, Yong Chen, Chenjie Zhu, Zhenyu Wang, Dong Liu, Hanjie Ying","doi":"10.1002/biot.70224","DOIUrl":"10.1002/biot.70224","url":null,"abstract":"<div>\u0000 \u0000 Microbial cell factories for the production of valuable chemicals often require multi-step biosynthetic pathways, whose efficiency is frequently limited by the performance and compatibility of pathway enzymes. Here, an isozyme co-expression strategy was proposed and evaluated in the (R)-1,3-BDO biosynthetic pathway of Escherichia coli. First, nine strains harboring different combinations of three candidate thiolases (AtoB, PhaA, Thl) and three candidate aldehyde dehydrogenases (Bld, Ald, AdhE2) were constructed and evaluated. Among them, the Thl-PhaB-Bld strain (B3-7) exhibited the highest (R)-1,3-BDO production (1.4 g/L). The remaining isozymes (AtoB, PhaA, Ald, and AdhE2) were then overexpressed individually in strain B3-7, with PhaA and AdhE2 showing the most significant improvement in (R)-1,3-BDO production. Co-expression of PhaA and AdhE2 further increased the (R)-1,3-BDO titer to 4.2 g/L, representing a 200% increase relative to strain B3-7. In addition, several metabolic effector molecules were screened as medium supplements, among which citric acid was identified as the most effective for improving (R)-1,3-BDO production. Finally, in glucose-feeding shake-flask fermentation, the isozyme co-expression strain produced 16.2 g/L (R)-1,3-BDO. Collectively, the isozyme co-expression strategy effectively enhanced (R)-1,3-BDO production and represents a promising approach for optimizing multi-step biosynthetic pathways.\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147631992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advanced Extractables and Leachables Assessment of Microcarriers Used for Adherent Cell Cultures 用于贴壁细胞培养的微载体的先进萃取物和浸出物评估。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-04-05 DOI: 10.1002/biot.70220

Armin Hauk, Ina Pahl, Jonas Austerjost, Julia Hupfeld, Julia Bernfeld, Antonina Lavrentieva, Roberto Menzel

{"title":"Advanced Extractables and Leachables Assessment of Microcarriers Used for Adherent Cell Cultures","authors":"Armin Hauk, Ina Pahl, Jonas Austerjost, Julia Hupfeld, Julia Bernfeld, Antonina Lavrentieva, Roberto Menzel","doi":"10.1002/biot.70220","DOIUrl":"10.1002/biot.70220","url":null,"abstract":"The study outlines principles and workflows for a comprehensive extractables and leachables qualification trial of microcarriers for use in a cell therapy application. Styrene-based MCs were qualitatively and quantitatively analyzed in accordance with USP 〈665〉, followed by a kinetic investigation. Extractables data were fitted to an algorithm to enable reconstructive modeling of dynamic experimental data for both stable and degradable extractables. In a subsequent step, the temporal exposure to process equipment-related leachables (PERLs) was modeled for MCs used in a hypothetical cell therapy application with partial and continuous medium exchange. The results demonstrated that, in a dynamic environment, the release of PERLs from MCs in a perfused system does not influence product quality at levels that would pose a patient safety risk. Furthermore, process concentrations remain significantly below exposure levels that could have detrimental effects on therapeutic human cells. This demonstrates the benefits of perfused systems, or systems with partial medium exchange, as the washout effect dominates PERL release rates. PERL concentrations in such dynamic systems will always be significantly lower than PERL equilibrium concentrations under static, stagnant conditions.","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/biot.70220","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147621280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Issue Information: Biotechnology Journal 4/2026 期刊信息：Biotechnology Journal 4/2026

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-04-04 DOI: 10.1002/biot.70221

引用次数: 0

Autotransduction and Pseudotyping as a Key Limitations in Lentiviral Vector Production 自转导和假分型是慢病毒载体生产的关键限制。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-04-04 DOI: 10.1002/biot.70219

Filip Walczak, Anna Szymkiewicz, Ilona Pacak, Artur Kowalik

{"title":"Autotransduction and Pseudotyping as a Key Limitations in Lentiviral Vector Production","authors":"Filip Walczak, Anna Szymkiewicz, Ilona Pacak, Artur Kowalik","doi":"10.1002/biot.70219","DOIUrl":"10.1002/biot.70219","url":null,"abstract":"<div>\u0000 \u0000 Lentiviral vectors are one of the important tools used in gene and cell therapy. Vector production involves a process known as pseudotyping, whereby glycoproteins originally derived from other viruses are incorporated into the envelope of the vector. The production of lentiviral vectors is associated with the risk of autotransduction. This phenomenon can cause genetic changes in the producer cells, loss of vector particles, and overproduction of transgenic proteins. This review article presents the phenomenon of autotransduction and the factors that influence its intensity. The review focuses on various viral envelopes, as different pseudotypes have been observed to interact differently with entry receptors. In addition to the classical VSV-G pseudotype, attention has also been directed toward alternative pseudotypes and viral envelopes, including GALV, BaEV, HERV-W, CNV-G, PRV-G, HA Rostock, Sendai virus, Sindbis virus, KoRV, LCMV, NiV, and RD114-pro. Particular emphasis has been placed on the low-density lipoprotein receptor, which is currently the most thoroughly characterized viral entry receptor. Furthermore, this review explores strategies aimed at minimizing autotransduction. In addition, we highlight key areas that warrant further investigation regarding lentiviral vector production.\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 4","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep Learning as a Compass for Industrial Biocatalysis: The Grase Framework Rewrites the Rules for Polyurethane Recycling 深度学习作为工业生物催化的指南针：Grase框架重写了聚氨酯回收规则。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-04-04 DOI: 10.1002/biot.70222

Lijun Wu, Lei Wang, Fan Wang, Weiyao Hu, Haibo Zhang

引用次数: 0

Front Cover: In Vivo Multi-Enzymatic Catalysis for Bioproduction of L-Lactic Acid from Sole Methanol 封面：单甲醇生物生产l -乳酸的体内多酶催化

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-04-04 DOI: 10.1002/biot.70223

Yunxia Li, Wei Yu, Lin Shan, Xiaoxin Zhai, Fan Yang, Hongwei Luan, Jiaoqi Gao, Yongjin J. Zhou

引用次数: 0

Analytical Centrifugal Ultrafiltration as a Tool for High Throughput Process Development in Virus Removal Filtration. 分析离心超滤作为高通量病毒去除过滤工艺开发的工具。

IF 3.1 3区生物学

Biotechnology Journal Pub Date : 2026-04-01 DOI: 10.1002/biot.70227

Sebastien Maffeis, Yuliia Fomichova, Levon Manukyan, Albert Mihranyan

{"title":"Analytical Centrifugal Ultrafiltration as a Tool for High Throughput Process Development in Virus Removal Filtration.","authors":"Sebastien Maffeis, Yuliia Fomichova, Levon Manukyan, Albert Mihranyan","doi":"10.1002/biot.70227","DOIUrl":"10.1002/biot.70227","url":null,"abstract":"Virus removal filtration constitutes an essential component in biopharmaceutical manufacturing processes for both recombinant and plasma-derived protein products. The increasing demand for protein-based therapies necessitates expedited analytical screening methodologies for virus filtration materials and process parameters utilizing high-throughput development (HTPD) platforms. This study examines a novel HTPD methodology, specifically the implementation of analytical centrifugal ultrafiltration, as a scaled-down virus removal filtration tool. A nanocellulose-derived filter membrane of controlled porosity (33 µm thickness, 23 nm) was integrated into a centrifugal ultrafiltration apparatus. The system underwent comprehensive evaluation to determine centrifugal ultrafiltration flux characteristics, product yield across varying buffer viscosities, virus removal capacity utilizing model MS2 (27 nm) and ΦX174 (28 nm) bacteriophages, and IgG throughput capacity. Application of centrifugal force facilitated the generation of multiple filtration pressure gradients suitable for small-volume sample processing. The resultant flux decay profiles exhibited high reproducibility, demonstrating superior IgG throughput and virus removal efficiency. Overall, the approach adds value to the arsenal of analytical tools useful for HTPD in biopharmaceutics.","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 4","pages":"e70227"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147696941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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