Journal of biotechnology最新文献_第10页

Developing a robust and scalable platform for AAV8 production 为AAV8生产开发一个健壮且可扩展的平台。

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-09-09 DOI: 10.1016/j.jbiotec.2025.09.002

André Nascimento , Tiago Q. Faria , Tiago Nunes , Joana G. Oliveira , José Mendes , António Roldão , Cristina Peixoto

{"title":"Developing a robust and scalable platform for AAV8 production","authors":"André Nascimento , Tiago Q. Faria , Tiago Nunes , Joana G. Oliveira , José Mendes , António Roldão , Cristina Peixoto","doi":"10.1016/j.jbiotec.2025.09.002","DOIUrl":"10.1016/j.jbiotec.2025.09.002","url":null,"abstract":"<div><div>Creating robust and scalable bioprocesses is essential for the production of viral vectors, particularly adeno-associated virus (AAV), which are in growing demand for gene therapy applications. This study presents the design and implementation of a scalable AAV8 production platform, leveraging extensive in-house expertise. Three production campaigns were conducted: two at the 2-liter scale and one at the 50-liter scale. The robustness of the upstream and downstream processes was confirmed in the 2-liter campaigns, yielding consistent titers and recoveries close to 80 %. Scalability was validated, demonstrating successful translation from the 2–50 L scale without compromising titers, recoveries, or product quality with a 3-fold enrichment of full capsids. Key modifications, such as adjustments to inoculation concentration, the choice of nuclease, and the direct loading of clarified material onto affinity chromatography, were evaluated to enhance process economics. These modifications did not adversely impact the production process and resulted in significant cost savings. Noteworthy, this study highlights a three-fold enrichment of full capsids, showcasing the process's ability to deliver a higher quality product. While the process is optimized for AAV8, only the polishing step is serotype-specific. The rest of the operations can be broadly applied to other AAV serotypes with minor adjustments. This flexibility suggests potential for wider applications in gene therapy and other fields.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 72-79"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040267","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

Enhancement of natamycin production in Streptomyces gilvosporeus through heavy ion beam mutagenesis and global transcription machinery engineering 通过重离子束诱变和全局转录机械工程提高gilvosporeus链霉菌纳他霉素的产量。

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-10-03 DOI: 10.1016/j.jbiotec.2025.09.017

Yuxiu Xu , Liang Wang , Wei Hu , Jian Xue , Wen Xiao , Hongjian Zhang , Jianhua Zhang , Xusheng Chen

{"title":"Enhancement of natamycin production in Streptomyces gilvosporeus through heavy ion beam mutagenesis and global transcription machinery engineering","authors":"Yuxiu Xu , Liang Wang , Wei Hu , Jian Xue , Wen Xiao , Hongjian Zhang , Jianhua Zhang , Xusheng Chen","doi":"10.1016/j.jbiotec.2025.09.017","DOIUrl":"10.1016/j.jbiotec.2025.09.017","url":null,"abstract":"<div><div>Natamycin is an antifungal agent produced by <em>Streptomyces</em> and is widely used in food, pharmaceuticals, and other fields. However, the low production of natamycin limits its application in various fields, making it crucial to enhance the biosynthetic capacity of natamycin-producing strains. In this study, <em>Streptomyces gilvosporeus</em> ATCC 13326 was used to construct a chassis for the efficient production of natamycin through strain engineering. A mutant strain <em>S. gilvosporeus</em> Z1403 with a titer of 1.7 g·L<sup>−1</sup> was obtained by heavy ion beam radiation and LiCl resistance screening, 70.0 % higher than that of the wild-type strain <em>S. gilvosporeus</em> ATCC 13326. Subsequently, transcription factor screening identified <em>whiG</em> as a key regulator of natamycin biosynthesis. Targeting <em>whiG</em> via global transcription machinery engineering further enhanced natamycin production of <em>S. gilvosporeus</em> Z1403. Finally, the high-production mutant strain EP-whiG was obtained with a titer of 2.2 g·L<sup>−1</sup>, 29.4 % and 120.0 % higher than that of the parent strain <em>S. gilvosporeus</em> Z1403 and the wild-type strain, respectively. <em>S. gilvosporeus</em> EP-whiG achieved a natamycin production of 13.1 g·L<sup>−1</sup> in a 5-L bioreactor within 120 h by fed-batch fermentation, which was 61.7 % higher than that of the wild-type strain. These results suggest that combining heavy ion beam mutagenesis with global transcription machinery engineering is an effective strategy for strain improvement, laying a theoretical foundation for enhancing the production of secondary metabolites in <em>Streptomyces</em>.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 254-264"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145232628","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

Preparation of high-purity 1,3-distearoyl-2-oleoylglycerol (StOSt) via a two-step enzymatic interesterification combined with two-step solvent fractionation 两步酶催化酯化结合两步溶剂分离制备高纯度1,3-二硬脂酰-2-油基甘油（StOSt）

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-09-03 DOI: 10.1016/j.jbiotec.2025.08.016

Chaeyeon Lee , Sopark Sonwai , Junsoo Lee , Byung Hee Kim , Heon-Woong Kim , In-Hwan Kim

{"title":"Preparation of high-purity 1,3-distearoyl-2-oleoylglycerol (StOSt) via a two-step enzymatic interesterification combined with two-step solvent fractionation","authors":"Chaeyeon Lee , Sopark Sonwai , Junsoo Lee , Byung Hee Kim , Heon-Woong Kim , In-Hwan Kim","doi":"10.1016/j.jbiotec.2025.08.016","DOIUrl":"10.1016/j.jbiotec.2025.08.016","url":null,"abstract":"<div><div>High-purity 1,3-distearoyl-2-oleoylglycerol (StOSt) was produced from high-oleic sunflower oil and ethyl stearate via a two-step enzymatic interesterification combined with a two-step solvent fractionation. Lipozyme RM IM (Rhizomucor miehei) was employed as a biocatalyst and the reaction was conducted in a packed-bed reactor. Molecular distillation was used to remove fatty acid ethyl esters from the reaction mixtures after enzymatic reactions. The optimum conditions were a temperature of 55 °C, a water content of 300 ppm (based on the total weight of the substrate), and a molar ratio of 1:8 (triacylglycerol (TAG) to ethyl stearate). The second enzymatic interesterification was carried out under the optimum conditions, resulting in the synthesis of 67.8 % StOSt-enriched TAG. To further enrich StOSt, two rounds of solvent fractionation were conducted using n-hexane and acetone, respectively. Consequently, StOSt TAG with a high purity of 83 % was achieved through the processes designed in this study.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 50-60"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005135","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 novel dynamic flux balance analysis for modeling CHO cell fed-batch cultures with pH and temperature shifts 一种新的动态通量平衡分析，用于模拟pH和温度变化的CHO细胞补料批培养。

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-09-04 DOI: 10.1016/j.jbiotec.2025.08.010

Ali Ghodba , Anne Richelle , Chris McCready , Luis Ricardez-Sandoval , Hector Budman

{"title":"A novel dynamic flux balance analysis for modeling CHO cell fed-batch cultures with pH and temperature shifts","authors":"Ali Ghodba , Anne Richelle , Chris McCready , Luis Ricardez-Sandoval , Hector Budman","doi":"10.1016/j.jbiotec.2025.08.010","DOIUrl":"10.1016/j.jbiotec.2025.08.010","url":null,"abstract":"<div><div>While Dynamic Flux Balance Analysis provides a powerful framework for simulating metabolic behavior, incorporating operating conditions such as pH and temperature, which profoundly impact monoclonal antibodies production, remains challenging. This study presents an advanced dFBA model that integrates kinetic constraints formulated as functions of pH and temperature to predict CHO cell metabolism under varying operational conditions. The model was validated against data from 20 fed-batch experiments conducted in Ambr®250 bioreactors. To mitigate overparameterization, a bi-level optimization approach utilizing the Bayesian Information Criterion was employed to systematically identify the most effective kinetic constraints. This optimization reduced the number of parameters (from 253 to 205) while improving predictive accuracy by up to 8.3% for training and 2.68% for validation datasets. The results highlight the model’s ability to predict cell growth, titer, and also capture metabolic shifts, including glucose, lactate, and ammonia metabolism and amino acid utilization, across different temperature and pH conditions with high predictive precision (average <span><math><mrow><msup><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msup><mo>≥</mo><mn>0</mn><mo>.</mo><mn>97</mn></mrow></math></span> for cell growth and titer and average <span><math><mrow><msup><mrow><mi>R</mi></mrow><mrow><mn>2</mn></mrow></msup><mo>≥</mo><mn>0</mn><mo>.</mo><mn>85</mn></mrow></math></span> for other metabolites). This optimized dFBA framework offers a robust tool for studying model-based optimization for CHO cell metabolism, identifying optimal operating conditions to balance growth and productivity.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 61-71"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008251","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

Microalgae in 3D bioprinting and bone regeneration: Trends, applications, and future perspectives 微藻在3D生物打印和骨再生：趋势，应用和未来展望。

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-08-29 DOI: 10.1016/j.jbiotec.2025.08.011

Qi Zhang , Gang Wang , Yuelei Zhang , Sheng Huang , Jiangxin Wang

{"title":"Microalgae in 3D bioprinting and bone regeneration: Trends, applications, and future perspectives","authors":"Qi Zhang , Gang Wang , Yuelei Zhang , Sheng Huang , Jiangxin Wang","doi":"10.1016/j.jbiotec.2025.08.011","DOIUrl":"10.1016/j.jbiotec.2025.08.011","url":null,"abstract":"<div><div>3D bioprinting has emerged as a powerful technology for bone tissue engineering, enabling the fabrication of complex, cell-laden structures with spatial precision. In recent years, microalgae have attracted growing attention in this field due to their unique photosynthetic ability, oxygen-generating capacity, and inherent bioactivities, which can enhance tissue regeneration and angiogenesis. This review systematically outlines the types of microalgae used in bone-related 3D bioprinting, their integration into bioinks and scaffolds, and the mechanisms through which they contribute to bone healing. Compared with previous literature, this review highlights underexplored dimensions such as the immunoregulatory properties of algal-derived scaffolds, the strategies to overcome their limited mechanical strength and immunogenicity<strong>,</strong> and the potential of genetic and material engineering to enhance clinical applicability. Furthermore, we discuss recent advancements in algal-laden scaffold sterilization methods—a critical but often overlooked aspect for clinical translation. A phenotypic–mechanistic integration framework and visual workflow diagrams are provided to aid material selection and design. Finally, we identify current limitations, research gaps, and future directions for utilizing microalgae as functional components in next-generation bioinks. These insights aim to promote the rational design of photosynthetically active and regenerative scaffolds for bone and soft tissue repair.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 121-131"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144955285","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

Reduction of high mannose glycoforms from monoclonal antibodies by affinity chromatography using a recombinant prokaryotic lectin 利用重组原核凝集素亲和层析法从单克隆抗体中还原高甘露糖糖型。

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-09-18 DOI: 10.1016/j.jbiotec.2025.09.008

Elizabeth Matthews , Neha Tushar Dalvi , Michael Butler

{"title":"Reduction of high mannose glycoforms from monoclonal antibodies by affinity chromatography using a recombinant prokaryotic lectin","authors":"Elizabeth Matthews , Neha Tushar Dalvi , Michael Butler","doi":"10.1016/j.jbiotec.2025.09.008","DOIUrl":"10.1016/j.jbiotec.2025.09.008","url":null,"abstract":"<div><div>Glycan profiles of monoclonal antibodies are critical quality attributes for their use as therapeutic agents. However, the control of glycosylation can prove difficult during large-scale manufacture. An on-going problem is the increase in high-mannose glycans (HM) that can occur unexpectedly under cell culture conditions that disrupt the glycosylation pathway. We have developed a method for removal of high-mannose glycans from a heterogeneous mixture of mAb glycoforms purified from a bioprocess. This involves the use of a prokaryotic lectin (RPL-Man2) bound to agarose beads to selectively bind reversibly to mAbs carrying HM-glycans. The unbound flow-through from this step contains the remainder of the mAb preparation with a reduced HM-glycan content. In this paper we demonstrate the application of this method using two distinct antibodies derived from Chinese hamster ovary (CHO) cells purposely grown under conditions that enhanced the content of HM-glycans. The presence of an elevated level of mannose in the culture of the producer cells as well as supplementation with a specific mannosidase inhibitor resulted in purified mAbs containing significantly higher levels of HM-glycans than would be expected normally under standard conditions. We showed that HM-glycans in the purified mAbs were reduced significantly by the application of lectin chromatography. Analysis by both UPLC using fluorescence detection as well as by mass spectrometry showed that the removal of the HM-glycoforms was selective and did not affect the profile of the remaining glycoforms. This method has potential for use in large-scale biomanufacturing for the reduction or elimination of HM-glycoforms of mAbs.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 158-167"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102709","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

Genome-scale metabolic analysis reveals enhanced metabolism and antioxidative stress response in perfusion cell culture under constant hyperosmotic stimulation 基因组尺度的代谢分析揭示了持续高渗刺激下灌注细胞培养中代谢和抗氧化应激反应的增强。

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-09-22 DOI: 10.1016/j.jbiotec.2025.09.010

Qingyuan Ran , Xinran Zhang , Chen Wang , Weijian Zhang , Liang Zhao , Wen-Song Tan , Qian Ye

{"title":"Genome-scale metabolic analysis reveals enhanced metabolism and antioxidative stress response in perfusion cell culture under constant hyperosmotic stimulation","authors":"Qingyuan Ran , Xinran Zhang , Chen Wang , Weijian Zhang , Liang Zhao , Wen-Song Tan , Qian Ye","doi":"10.1016/j.jbiotec.2025.09.010","DOIUrl":"10.1016/j.jbiotec.2025.09.010","url":null,"abstract":"<div><div>Hyperosmotic stimulation is a prevalent strategy to enhance cell culture productivity in fed-batch cultures. Maintaining stable hyperosmotic conditions during perfusion cultures presents a promising strategy, but research on its application in perfusion processes remains limited. In this study, we investigated cellular responses under constant hyperosmolality in Chinese hamster ovary (CHO) cell perfusion cultures using Raman spectroscopy to maintain a constant hyperosmotic environment. Integrated genome-scale metabolic model (GEM) with real-time monitoring of the oxygen uptake rate (OUR) was employed to systematically analyze the metabolic alterations induced by constant hyperosmotic stimulation. Our findings showed that the CHO cells exhibited time-dependent metabolic responses, with rapid changes in nutrient uptake, glycolysis, and TCA cycle activity, while lactate metabolism responded more slowly. The specific productivity (<em>q</em><sub><em>mAb</em></sub>) displayed the slowest changes, stabilizing only after 6–9 days upon the simulation, resulting in a maximum increase up to 168.5 %. Notably, we found shifts in the intracellular redox environment, and the cells enhanced their antioxidative capacity at low dissolved oxygen (DO) levels under hyperosmotic conditions. Even when DO dropped to 10 %, the cells subjected to hyperosmotic stimulation maintained relatively low levels of reactive oxygen species (ROS) while preserving high <em>q</em><sub><em>mAb</em></sub>. Overall, this study provides new insights into cellular responses under constant hyperosmotic condition and provides insights for the application of hyperosmotic strategies in perfusion processes.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 181-191"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137658","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

Optimizing lignocellulose conversion: A comparative study of alkali-assisted ball milling pretreatment of cotton stalk and corn stover 优化木质纤维素转化：碱辅助球磨预处理棉秆和玉米秸秆的比较研究

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-09-04 DOI: 10.1016/j.jbiotec.2025.08.018

Hui Zhang , Xiwen Jia , Kaili Ding , Xueyan Liang , Yinghui He , Xiaojun Guo , Ling Zhou , Lujia Han , Weihua Xiao

{"title":"Optimizing lignocellulose conversion: A comparative study of alkali-assisted ball milling pretreatment of cotton stalk and corn stover","authors":"Hui Zhang , Xiwen Jia , Kaili Ding , Xueyan Liang , Yinghui He , Xiaojun Guo , Ling Zhou , Lujia Han , Weihua Xiao","doi":"10.1016/j.jbiotec.2025.08.018","DOIUrl":"10.1016/j.jbiotec.2025.08.018","url":null,"abstract":"<div><div>Cotton stalk (CTS) and corn stover (CRS) were pretreated using solid alkali (NaOH or Ca(OH)<sub>2</sub>) assisted ball milling (BM). The physicochemical properties of the pretreated materials and their high-solid enzymatic hydrolysis performance were systematically investigated. The interaction between alkali and straw was synergistically enhanced by mechanical force generated during BM, achieving effective lignin removal. NaOH showed superior delignification efficiency compared to Ca(OH)<sub>2</sub> for both straws at same dosages. Analysis of cation exchange capacity revealed higher stability of CTS-Ca<sup>2</sup><sup>+</sup> complex than CRS-Ca<sup>2+</sup> complex, explaining the more effective lignin removal from CTS than from CRS by Ca(OH)<sub>2</sub>. During the alkali/BM process, cellulose showed structural swelling and crystalline destruction. The cellulose of CTS mainly retained its cellulose I crystallinity, whereas most of the cellulose of CRS was converted to an amorphous state. The changes in physicochemical properties and structure effectively improved the enzymatic saccharification efficiency of pretreated straws. Under high-solids loading conditions (20 %) with an enzyme loading of 20 FPU/g, the maximum glucose yields from NaOH-pretreated and Ca(OH)<sub>2</sub>-pretreated CTS were 68.52 % and 65.90 %, respectively. The corresponding yields for CRS were 80.43 % and 80.30 %. Partial least squares (PLS) analysis identified straw composition, particularly changes in cellulose, as the dominant factor influencing enzymatic hydrolysis efficiency. This study provided valuable insights for optimizing biomass-specific pretreatment strategies to achieve efficient sugar production.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 15-27"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997605","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 review on microbial metabolic engineering for the improvement of itaconic acid production 改善衣康酸生产的微生物代谢工程研究进展

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-09-03 DOI: 10.1016/j.jbiotec.2025.08.017

Yanhua Zhang , Tianqi Han , Wenlong Qu , Xiaolu Wang , Depei Wang , Xianli Xue

{"title":"A review on microbial metabolic engineering for the improvement of itaconic acid production","authors":"Yanhua Zhang , Tianqi Han , Wenlong Qu , Xiaolu Wang , Depei Wang , Xianli Xue","doi":"10.1016/j.jbiotec.2025.08.017","DOIUrl":"10.1016/j.jbiotec.2025.08.017","url":null,"abstract":"<div><div>Itaconic acid (IA), also known as methylene-butanedioic acid, is one of the top 12 platform chemicals in the world and demand for it is growing worldwide. The itaconic acid molecule contains one reactive double bond and two carboxyl groups, endowing it with chemical reactivity. It is widely used in fields such as light industry, agriculture, energy, and medical applications. The recent progress in understanding the biosynthesis, the regulation and the cellular transport of itaconic acid has facilitated the optimisation of existing processes as well as the construction of new microbial platforms. However, there is still need for further optimisation to increase the space-time yield, to achieve higher final concentrations and to use a broader range of low cost sustainable raw materials. In this review article, we have summarized the current status of itaconic acid production by natural microbial strains, recent advances in research on genetically engineered modified strains, and further analyzed the gene clusters associated with itaconic acid biosynthesis in <em>Aspergillus terreus</em>, <em>Ustilago maydis</em>, as well as similar genetic clusters identified in <em>A. niger</em>. Genetic engineering and process development need to apply intelligent screening platforms to obtain as much information as possible in small scale so as to provide more detailed basic information and newer improvement ideas for subsequent research.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 28-38"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004677","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

Optimizing Chlorella vulgaris production and exploring its impact on germination through microalga-N2-fixing bacteria consortia 优化小球藻产量及探讨微藻-固氮菌群对其萌发的影响。

IF 3.9 2区生物学

Journal of biotechnology Pub Date : 2025-12-01 Epub Date: 2025-10-01 DOI: 10.1016/j.jbiotec.2025.09.018

Ana Sanchez-Zurano , Silvia Vilaró-Cos , Daniel Figueiredo , Lusine Melkonyan , Alice Ferreira , Francisco Gabriel Acién , Tomas Lafarga , Luisa Gouveia

{"title":"Optimizing Chlorella vulgaris production and exploring its impact on germination through microalga-N2-fixing bacteria consortia","authors":"Ana Sanchez-Zurano , Silvia Vilaró-Cos , Daniel Figueiredo , Lusine Melkonyan , Alice Ferreira , Francisco Gabriel Acién , Tomas Lafarga , Luisa Gouveia","doi":"10.1016/j.jbiotec.2025.09.018","DOIUrl":"10.1016/j.jbiotec.2025.09.018","url":null,"abstract":"<div><div>Microalgal biomass is increasingly valued in industrial and agricultural sectors due to its bioactive compounds. However, large-scale production remains costly, mainly due to nitrogen fertilizer expenses. A promising sustainable alternative is co-cultivation with N<sub>2</sub>-fixing bacteria, capable of supplying biologically available nitrogen. In this study, <em>Chlorella vulgaris</em> was grown in synthetic medium with and without nitrogen, as well as in co-culture with three different N<sub>2</sub>-fixing bacteria in nitrogen-free medium. Microalgal growth was assessed by dry weight, <em>Fv/Fm</em> ratio, and flow cytometry, which also allowed evaluation of population dynamics and cell viability. Biomass composition (proteins, carbohydrates, lipids, chlorophyll, and carotenoids) was analyzed under all conditions. Co-cultures in nitrogen-free medium showed comparable biomass productivity to nitrogen-supplemented controls, although <em>Fv/Fm</em> values indicated physiological stress in some cases. Moreover, the agricultural potential of the resulting biomass and supernatants was evaluated through germination bioassays using lettuce seeds. All cultures tested at 0.2 g·L<sup>−1</sup> significantly improved the germination index. Also, applying the culture supernatant (biomass removed) also yielded positive effects, with GI increases exceeding 40 %. These results suggest that co-cultivation with N<sub>2</sub>-fixing bacteria can support efficient microalgal production while generating biomass and supernatants with biostimulant potential, contributing to sustainable agriculture and circular bioeconomy strategies.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"408 ","pages":"Pages 244-253"},"PeriodicalIF":3.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225246","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