The use of microalgae to produce renewable biomass is a promising approach to addressing environmental and energy challenges, but the high cost of microalgae harvesting limits its industrial application. To explore the efficient and low-cost harvesting of microalgae, a novel method utilizing fenugreek gum for bubble-free harvesting was developed. Single-factor experiments and response surface analysis were used to screen the significant influencing factors. A multi-objective optimization model was established to determine the key factors influencing harvesting efficiency, including pH, sodium cellulose addition, stirring time, stirring speed, flotation material addition, and raw algal volume. This resulted in an optimal harvesting efficiency of 94.026% and an optimal enrichment ratio of 2.5%. Based on the life cycle evaluation, it was concluded that the environmental impact of fenugreek gum on climate change was 1.14kg CO2 eq, and the production cost was $3.15, which was significantly lower than the traditional harvesting method. Mechanistic Analysis indicates that the adhesion of fenugreek gum to microalgae is achieved through an electrostatic neutralization and adsorption bridging mechanism.
{"title":"Analysis of Fenugreek gum-based microalgae harvesting technology and its mechanism of action.","authors":"Xichen Zheng, Hao Wen, Kemin Wei, Jia He, Manli Wang, Meili Wu","doi":"10.1016/j.jbiotec.2026.02.002","DOIUrl":"https://doi.org/10.1016/j.jbiotec.2026.02.002","url":null,"abstract":"<p><p>The use of microalgae to produce renewable biomass is a promising approach to addressing environmental and energy challenges, but the high cost of microalgae harvesting limits its industrial application. To explore the efficient and low-cost harvesting of microalgae, a novel method utilizing fenugreek gum for bubble-free harvesting was developed. Single-factor experiments and response surface analysis were used to screen the significant influencing factors. A multi-objective optimization model was established to determine the key factors influencing harvesting efficiency, including pH, sodium cellulose addition, stirring time, stirring speed, flotation material addition, and raw algal volume. This resulted in an optimal harvesting efficiency of 94.026% and an optimal enrichment ratio of 2.5%. Based on the life cycle evaluation, it was concluded that the environmental impact of fenugreek gum on climate change was 1.14kg CO<sub>2</sub> eq, and the production cost was $3.15, which was significantly lower than the traditional harvesting method. Mechanistic Analysis indicates that the adhesion of fenugreek gum to microalgae is achieved through an electrostatic neutralization and adsorption bridging mechanism.</p>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":" ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142549","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}
Pub Date : 2026-01-30DOI: 10.1016/j.jbiotec.2026.01.016
Chae Eun Lee, Sohee Lim, Da Won Lee, Jong Seok Lim, Jin Wook Kim, Soon Auck Hong, Hye Jun Lee, Kisung Ko, Soon Chul Myung
Plant-based biopharmaceutical platforms offer a cost-effective and scalable alternative for therapeutic antibody production. In this study, transgenic Nicotiana tabacum (N. tabacum) plants were generated to express pembrolizumab, an anti-human programmed cell death protein-1 (PD-1) monoclonal antibody (mAb), targeting both classical PD-1 on immune cells and the recently identified intrinsic PD-1 (iPD-1) variant in tumor cells. The plant-derived anti-PD-1 mAb (mAbP PD-1) was successfully purified and validated through SDS-PAGE and immunoblotting. Functional analyses using ELISA and immunohistochemistry demonstrated that mAbP PD-1 exhibits strong binding affinity to recombinant human PD-1 and efficiently detects PD-1 expression in human tonsil tissue. Importantly, cell-based assays demonstrated that mAbP PD-1 binds effectively to iPD-1-expressing bladder urothelial cancer cell lines, resulting in significant inhibition of cell proliferation. Mechanistically, Western blot analysis revealed that mAbP PD-1 markedly suppresses extracellular signal-regulated kinase (ERK) phosphorylation without altering total ERK levels, indicating direct modulation of the mitogen-activated protein kinase (MAPK) signaling pathway associated with tumor cell proliferation. These findings establish transgenic tobacco plants as a cost-effective and scalable platform for producing functional anti-PD-1 antibodies with potent immunoregulatory and anti-proliferative properties. The dual targeting of immune cell PD-1 and tumor cell iPD-1 underscores the therapeutic potential of plant-derived antibodies in cancer immunotherapy.
{"title":"Expression and functional analysis of anti-human PD-1 monoclonal antibody in transgenic plants.","authors":"Chae Eun Lee, Sohee Lim, Da Won Lee, Jong Seok Lim, Jin Wook Kim, Soon Auck Hong, Hye Jun Lee, Kisung Ko, Soon Chul Myung","doi":"10.1016/j.jbiotec.2026.01.016","DOIUrl":"10.1016/j.jbiotec.2026.01.016","url":null,"abstract":"<p><p>Plant-based biopharmaceutical platforms offer a cost-effective and scalable alternative for therapeutic antibody production. In this study, transgenic Nicotiana tabacum (N. tabacum) plants were generated to express pembrolizumab, an anti-human programmed cell death protein-1 (PD-1) monoclonal antibody (mAb), targeting both classical PD-1 on immune cells and the recently identified intrinsic PD-1 (iPD-1) variant in tumor cells. The plant-derived anti-PD-1 mAb (mAb<sup>P</sup> PD-1) was successfully purified and validated through SDS-PAGE and immunoblotting. Functional analyses using ELISA and immunohistochemistry demonstrated that mAb<sup>P</sup> PD-1 exhibits strong binding affinity to recombinant human PD-1 and efficiently detects PD-1 expression in human tonsil tissue. Importantly, cell-based assays demonstrated that mAb<sup>P</sup> PD-1 binds effectively to iPD-1-expressing bladder urothelial cancer cell lines, resulting in significant inhibition of cell proliferation. Mechanistically, Western blot analysis revealed that mAb<sup>P</sup> PD-1 markedly suppresses extracellular signal-regulated kinase (ERK) phosphorylation without altering total ERK levels, indicating direct modulation of the mitogen-activated protein kinase (MAPK) signaling pathway associated with tumor cell proliferation. These findings establish transgenic tobacco plants as a cost-effective and scalable platform for producing functional anti-PD-1 antibodies with potent immunoregulatory and anti-proliferative properties. The dual targeting of immune cell PD-1 and tumor cell iPD-1 underscores the therapeutic potential of plant-derived antibodies in cancer immunotherapy.</p>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":" ","pages":"5-13"},"PeriodicalIF":3.9,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100262","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}
Pub Date : 2026-01-29DOI: 10.1016/j.jbiotec.2026.01.014
Kefa Hu , Zhipeng Qi , Xiaode Huang , Lei Wang , Xiaomeng Zhang , Shaoheng Tang
Lavandulol and its acetate ester, lavandulyl acetate, are valuable irregular monoterpenes found in lavender essential oil, widely utilized in the food and cosmetic industries. Due to the limitations of extraction from natural plant resources, developing sustainable microbial cell factories for their production is of great interest. Here, we report the first de novo biosynthesis of lavandulol and lavandulyl acetate in Escherichia coli. Initially, a heterologous mevalonate (MVA) pathway was coupled with lavandulyl diphosphate synthase (LPPS) to establish the biosynthetic route from glycerol. To relieve pathway bottlenecks, we overexpressed the endogenous dITP/XTP pyrophosphatase RdgB, which efficiently facilitated the dephosphorylation of the precursor lavandulyl diphosphate (LPP), increasing lavandulol titers to 42.87 mg/L. Subsequently, the alcohol acyltransferase ATF1 from Saccharomyces cerevisiae was identified as the most effective enzyme for acetylating lavandulol. By integrating ATF1 into the pathway and optimizing both the host strain and fermentation process, we achieved a final lavandulyl acetate titer of 89.43 mg/L. This study establishes a promising prokaryotic platform for the efficient biosynthesis of high-value irregular monoterpenes.
{"title":"De novo biosynthesis of lavandulol and lavandulyl acetate in Escherichia coli","authors":"Kefa Hu , Zhipeng Qi , Xiaode Huang , Lei Wang , Xiaomeng Zhang , Shaoheng Tang","doi":"10.1016/j.jbiotec.2026.01.014","DOIUrl":"10.1016/j.jbiotec.2026.01.014","url":null,"abstract":"<div><div>Lavandulol and its acetate ester, lavandulyl acetate, are valuable irregular monoterpenes found in lavender essential oil, widely utilized in the food and cosmetic industries. Due to the limitations of extraction from natural plant resources, developing sustainable microbial cell factories for their production is of great interest. Here, we report the first de novo biosynthesis of lavandulol and lavandulyl acetate in <em>Escherichia coli</em>. Initially, a heterologous mevalonate (MVA) pathway was coupled with lavandulyl diphosphate synthase (LPPS) to establish the biosynthetic route from glycerol. To relieve pathway bottlenecks, we overexpressed the endogenous dITP/XTP pyrophosphatase RdgB, which efficiently facilitated the dephosphorylation of the precursor lavandulyl diphosphate (LPP), increasing lavandulol titers to 42.87 mg/L. Subsequently, the alcohol acyltransferase ATF1 from <em>Saccharomyces cerevisiae</em> was identified as the most effective enzyme for acetylating lavandulol. By integrating ATF1 into the pathway and optimizing both the host strain and fermentation process, we achieved a final lavandulyl acetate titer of 89.43 mg/L. This study establishes a promising prokaryotic platform for the efficient biosynthesis of high-value irregular monoterpenes.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"411 ","pages":"Pages 144-151"},"PeriodicalIF":3.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074870","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}
Pub Date : 2026-01-29DOI: 10.1016/j.jbiotec.2026.01.015
Constance Keller , Rocio Cozmar , Miguel Alcalde , Patrick Fickers
For decades, Komagataella phaffii has been the reference host for recombinant secretory protein (rsProt) production. However, secretion bottlenecks associated with the limited processing capacity of the endoplasmic reticulum restrict the secretion efficiency under high protein loads. Besides, Yarrowia lipolytica possesses a secretion pathway resembling that of filamentous fungi and naturally secretes large amounts of hydrolytic enzymes, making it a promising alternative host. In this study, we systematically investigated the impact of pre- and pro-sequences on the secretion of LacVader, an evolved laccase with industrial applications. In Y. lipolytica, nine constructs combining four pre-sequences (αPre, Yps3Pre, Lip2Pre, SoAmyPre) and two pro-sequences (αPro, Lip2Pro) were integrated at the LIP2 locus and expressed under the constitutive PTEF promoter. Comparative analysis revealed that most pre–pro constructs resulted in higher laccase specific activity compared to K. phaffii expressing the enzyme under the canonical PAOX1 promoter and the S. cerevisiae α-factor signal peptide. Notably, both the pre- and pro-sequences had a strong influence on laccase secretion in Y. lipolytica. The Lip2Pro sequence consistently enhanced secretion, with the Yps3Pre–Lip2Pro construct yielding the highest activity, eightfold greater than that obtained in K. phaffii. These findings highlight the crucial role of secretion signal optimization in rsProt production and confirm the superior potential of Y. lipolytica over K. phaffii as a robust host for industrial enzyme secretion.
{"title":"Yarrowia lipolytica, Komagataella phaffii and secretory proteins: Recombinant laccase as a case study","authors":"Constance Keller , Rocio Cozmar , Miguel Alcalde , Patrick Fickers","doi":"10.1016/j.jbiotec.2026.01.015","DOIUrl":"10.1016/j.jbiotec.2026.01.015","url":null,"abstract":"<div><div>For decades, <em>Komagataella phaffii</em> has been the reference host for recombinant secretory protein (rsProt) production. However, secretion bottlenecks associated with the limited processing capacity of the endoplasmic reticulum restrict the secretion efficiency under high protein loads. Besides, <em>Yarrowia lipolytica</em> possesses a secretion pathway resembling that of filamentous fungi and naturally secretes large amounts of hydrolytic enzymes, making it a promising alternative host. In this study, we systematically investigated the impact of pre- and pro-sequences on the secretion of LacVader, an evolved laccase with industrial applications. In <em>Y. lipolytica</em>, nine constructs combining four pre-sequences (αPre, Yps3Pre, Lip2Pre, SoAmyPre) and two pro-sequences (αPro, Lip2Pro) were integrated at the <em>LIP2</em> locus and expressed under the constitutive P<sub>TEF</sub> promoter. Comparative analysis revealed that most pre–pro constructs resulted in higher laccase specific activity compared to <em>K. phaffii</em> expressing the enzyme under the canonical P<sub>AOX1</sub> promoter and the <em>S. cerevisiae</em> α-factor signal peptide. Notably, both the pre- and pro-sequences had a strong influence on laccase secretion in <em>Y. lipolytica</em>. The Lip2Pro sequence consistently enhanced secretion, with the Yps3Pre–Lip2Pro construct yielding the highest activity, eightfold greater than that obtained in <em>K. phaffii</em>. These findings highlight the crucial role of secretion signal optimization in rsProt production and confirm the superior potential of <em>Y. lipolytica</em> over <em>K. phaffii</em> as a robust host for industrial enzyme secretion.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"412 ","pages":"Pages 1-4"},"PeriodicalIF":3.9,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097119","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}
Pub Date : 2026-01-27DOI: 10.1016/j.jbiotec.2026.01.012
Michaela Dölle , Maxime Hervé , Staffan Königsson , Peter Thorwid , Johan Rockberg , Véronique Chotteau
Continuous centrifugation is a well-established method for clarifying mammalian cell cultures, but traditional batch-based approaches often fall short of modern biomanufacturing’s scalability and flexibility demands. Increasing variability in product volumes and manufacturing setups calls for adaptable, scalable solutions. To address this, we developed a scaled-down continuous centrifuge (“Mini”) based on a commercial disc-stack centrifuge, facilitating efficient early-stage development and improving technology transfer and scale-up. This study demonstrates the Mini’s potential to bridge the gap between small-scale optimization and industrial-scale centrifugation. Proof-of-concept experiments with Chinese hamster ovary cell culture confirmed its separation efficiency, achieving low turbidity, high product recovery (up to 98.5%), and minimal cell stress. Lactate dehydrogenase activity remained low, with a maximum increase in host cell proteins of 11.9% across various operating conditions. Validation experiments against the pilot-scale Culture One™ Primo showed comparable or superior turbidity reduction and lower lactate dehydrogenase activity, highlighting the Mini’s gentle cell handling. The Mini enables continuous small-scale centrifugation while replicating key performance parameters of the pilot-scale system, ensuring accurate performance predictions and reliable scale-up. It provides a scalable, flexible solution that meets the evolving needs of modern biomanufacturing for efficient and adaptable clarification processes.
{"title":"Efficiency and scalability in harvesting mammalian cell cultures: A scale-down approach to continuous centrifugation","authors":"Michaela Dölle , Maxime Hervé , Staffan Königsson , Peter Thorwid , Johan Rockberg , Véronique Chotteau","doi":"10.1016/j.jbiotec.2026.01.012","DOIUrl":"10.1016/j.jbiotec.2026.01.012","url":null,"abstract":"<div><div>Continuous centrifugation is a well-established method for clarifying mammalian cell cultures, but traditional batch-based approaches often fall short of modern biomanufacturing’s scalability and flexibility demands. Increasing variability in product volumes and manufacturing setups calls for adaptable, scalable solutions. To address this, we developed a scaled-down continuous centrifuge (“Mini”) based on a commercial disc-stack centrifuge, facilitating efficient early-stage development and improving technology transfer and scale-up. This study demonstrates the Mini’s potential to bridge the gap between small-scale optimization and industrial-scale centrifugation. Proof-of-concept experiments with Chinese hamster ovary cell culture confirmed its separation efficiency, achieving low turbidity, high product recovery (up to 98.5%), and minimal cell stress. Lactate dehydrogenase activity remained low, with a maximum increase in host cell proteins of 11.9% across various operating conditions. Validation experiments against the pilot-scale Culture One™ Primo showed comparable or superior turbidity reduction and lower lactate dehydrogenase activity, highlighting the Mini’s gentle cell handling. The Mini enables continuous small-scale centrifugation while replicating key performance parameters of the pilot-scale system, ensuring accurate performance predictions and reliable scale-up. It provides a scalable, flexible solution that meets the evolving needs of modern biomanufacturing for efficient and adaptable clarification processes.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"411 ","pages":"Pages 89-101"},"PeriodicalIF":3.9,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074868","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}
Soil salinization poses a critical threat to agricultural productivity, particularly in the Mediterranean regions where olive cultivation is of major economic and ecological significance. This study investigates the potential of phenolic extracts derived from olive mill solid waste (OMSW) to enhance salt stress tolerance in Olea europaea L. cv. Koroneiki. One-year-old olive plants were subjected to six treatments: a non-stressed control (C), phenolic extract application under non-stress conditions (C + PE-OMSW), OMSW amendment under non-stress conditions (C + OMSW), salt stress induced by 100 mM NaCl (SS), salt stress combined with phenolic extract (SS + PE-OMSW), and salt stress combined with OMSW (SS + OMSW). A comprehensive physiological and biochemical evaluation was conducted, including measurements of vegetative growth, relative water content, membrane stability, chlorophyll fluorescence, photosynthetic pigments, oxidative stress markers (malondialdehyde and hydrogen peroxide), osmoprotectants (proline and soluble sugars), total polyphenols, flavonoids, and leaf mineral content. Application of phenolic extract under saline conditions (SS + PE-OMSW) markedly improved plant performance by enhancing water status, preserving membrane integrity, and increasing chlorophyll fluorescence efficiency. These plants also exhibited higher polyphenols and flavonoids accumulation, along with significant reductions in oxidative stress markers, suggesting enhanced antioxidant defenses. Elevated levels of proline and soluble sugars further indicated an adaptive osmotic adjustment to salinity. These results demonstrate the efficacy of OMSW-derived phenolic extracts as sustainable biostimulants capable of mitigating salt stress through integrated physiological and biochemical mechanisms. This valorization pathway offers a promising approach to recycling agro-industrial residues into high-value agricultural inputs, contributing to climate-resilient and circular bioeconomy-based crop production systems.
土壤盐碱化对农业生产力构成严重威胁，特别是在橄榄树种植具有重大经济和生态意义的地中海地区。本研究探讨了橄榄厂固体废物（OMSW）酚类提取物提高油橄榄（Olea europaea L. cv）耐盐性的潜力。Koroneiki。对1年生橄榄植株进行6个处理：无胁迫对照(C)、无胁迫条件下施用酚类提取物（C + PE-OMSW）、无胁迫条件下添加OMSW （C + OMSW）、100 mM NaCl诱导盐胁迫（SS）、盐胁迫+酚类提取物（SS + PE-OMSW）、盐胁迫+ OMSW （SS + OMSW）。进行了全面的生理生化评价，包括营养生长、相对含水量、膜稳定性、叶绿素荧光、光合色素、氧化应激标志物（丙二醛和过氧化氢）、渗透保护剂（脯氨酸和可溶性糖）、总多酚、类黄酮和叶片矿物质含量的测定。在生理盐水条件下施用酚提取物（SS + PE-OMSW），通过改善水分状态、保持膜完整性和提高叶绿素荧光效率，显著改善了植物的生产性能。这些植物还表现出更高的多酚和类黄酮积累，以及氧化应激标志物的显著减少，表明抗氧化防御能力增强。脯氨酸和可溶性糖水平的升高进一步表明了对盐度的适应性渗透调节。这些结果表明，omsw衍生的酚类提取物作为一种可持续的生物刺激剂，能够通过综合的生理和生化机制缓解盐胁迫。这一增值途径为将农业工业残留物循环利用为高价值农业投入物提供了一种有希望的方法，有助于建立适应气候变化和基于循环生物经济的作物生产系统。
{"title":"Multilevel agro-physiological and biochemical alleviation of salt stress in Olea europaea via phenolic-rich extracts from olive mill waste","authors":"Samia Abboud , Nada Ammar , Azhar Ouni , Mourad Jellali , Darine Tlili , Sahar Ben Abdelwaheb , Amani Bchir , Soumaya Dbara","doi":"10.1016/j.jbiotec.2026.01.013","DOIUrl":"10.1016/j.jbiotec.2026.01.013","url":null,"abstract":"<div><div>Soil salinization poses a critical threat to agricultural productivity, particularly in the Mediterranean regions where olive cultivation is of major economic and ecological significance. This study investigates the potential of phenolic extracts derived from olive mill solid waste (OMSW) to enhance salt stress tolerance in Olea europaea L. cv. Koroneiki. One-year-old olive plants were subjected to six treatments: a non-stressed control (C), phenolic extract application under non-stress conditions (C + PE-OMSW), OMSW amendment under non-stress conditions (C + OMSW), salt stress induced by 100 mM NaCl (SS), salt stress combined with phenolic extract (SS + PE-OMSW), and salt stress combined with OMSW (SS + OMSW). A comprehensive physiological and biochemical evaluation was conducted, including measurements of vegetative growth, relative water content, membrane stability, chlorophyll fluorescence, photosynthetic pigments, oxidative stress markers (malondialdehyde and hydrogen peroxide), osmoprotectants (proline and soluble sugars), total polyphenols, flavonoids, and leaf mineral content. Application of phenolic extract under saline conditions (SS + PE-OMSW) markedly improved plant performance by enhancing water status, preserving membrane integrity, and increasing chlorophyll fluorescence efficiency. These plants also exhibited higher polyphenols and flavonoids accumulation, along with significant reductions in oxidative stress markers, suggesting enhanced antioxidant defenses. Elevated levels of proline and soluble sugars further indicated an adaptive osmotic adjustment to salinity. These results demonstrate the efficacy of OMSW-derived phenolic extracts as sustainable biostimulants capable of mitigating salt stress through integrated physiological and biochemical mechanisms. This valorization pathway offers a promising approach to recycling agro-industrial residues into high-value agricultural inputs, contributing to climate-resilient and circular bioeconomy-based crop production systems.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"411 ","pages":"Pages 116-129"},"PeriodicalIF":3.9,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074869","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}
Pub Date : 2026-01-25DOI: 10.1016/j.jbiotec.2026.01.010
Sneha Banerjee, Sreeja Vangapally, Anna Mariya, Bhaskar Paidimuddala
Bispecific nanobodies are the emerging class of engineered nanobodies with great scope for targeted therapy due to their small size, high stability, extended half-life, and dual antigenic recognition properties. They can bind to two different antigens simultaneously which significantly improves the therapeutic index in the treatment of various diseases. To achieve enhanced binding avidity, specificity and minimal off-target effects, the bispecific nanobodies have been further subjected to advanced engineering strategies such as site-specific combinations, fusions and multivalent formats. The recombinant production of bispecific nanobodies has been tested in bacterial, yeast and mammalian expression platforms to facilitate their large-scale production and cost-effective clinical applications. This review exclusively focuses on recent progress in the design and development of bispecific nanobodies. It presents the engineering of nanobodies into bispecific formats, their design, expression strategies and therapeutic outcomes. It also discusses the recent preclinical and clinical developments of bispecific nanobodies focusing on tackling half-life extension problems, reducing immunogenicity and optimal delivery modalities. Overall, with the promising scope of bispecific nanobodies as targeted therapies, their acceptance into mainstream medicine holds great promise for precision and personalized therapeutic approaches for the effective treatment of various infections, cancers, autoimmune and neurodegenerative diseases.
{"title":"Bispecific nanobodies – promising engineered candidates with high therapeutic efficiency","authors":"Sneha Banerjee, Sreeja Vangapally, Anna Mariya, Bhaskar Paidimuddala","doi":"10.1016/j.jbiotec.2026.01.010","DOIUrl":"10.1016/j.jbiotec.2026.01.010","url":null,"abstract":"<div><div>Bispecific nanobodies are the emerging class of engineered nanobodies with great scope for targeted therapy due to their small size, high stability, extended half-life, and dual antigenic recognition properties. They can bind to two different antigens simultaneously which significantly improves the therapeutic index in the treatment of various diseases. To achieve enhanced binding avidity, specificity and minimal off-target effects, the bispecific nanobodies have been further subjected to advanced engineering strategies such as site-specific combinations, fusions and multivalent formats. The recombinant production of bispecific nanobodies has been tested in bacterial, yeast and mammalian expression platforms to facilitate their large-scale production and cost-effective clinical applications. This review exclusively focuses on recent progress in the design and development of bispecific nanobodies. It presents the engineering of nanobodies into bispecific formats, their design, expression strategies and therapeutic outcomes. It also discusses the recent preclinical and clinical developments of bispecific nanobodies focusing on tackling half-life extension problems, reducing immunogenicity and optimal delivery modalities. Overall, with the promising scope of bispecific nanobodies as targeted therapies, their acceptance into mainstream medicine holds great promise for precision and personalized therapeutic approaches for the effective treatment of various infections, cancers, autoimmune and neurodegenerative diseases.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"411 ","pages":"Pages 102-115"},"PeriodicalIF":3.9,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146063078","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}
Pub Date : 2026-01-24DOI: 10.1016/j.jbiotec.2026.01.011
Li Zhang, Jianan Yang, Zhixuan Lv, Longjun Han, Zhiwei Zha, Zhijie Cheng, Xu Yang, Zhengyang Xu, Lei Yang, Jian Gao
Oxidative stress in Escherichia coli during chemical production, caused by reactive oxygen species (ROS), impairs cell viability and limits output. This study addressed product accumulation and ROS stress in L-lysine-producing strains. Genetic engineering created three variants: dynamically up-regulated R1, down-regulated R2, and temporally regulatable R3 to reduce ROS during fermentation. Under stress conditions, all engineered strains showed significantly lower ROS levels versus parental strain R0, with R3 exhibiting the greatest reduction. Fermentation confirmed R3's superior performance, yielding 85.8 % more L-lysine than R0. These results demonstrate that constructing ROS mitigator achieves precise ROS control and efficient L-lysine synthesis. This dynamic regulation strategy enhances cell viability and production performance under oxidative stress, providing a viable approach for improving engineered cell factories' stress resistance.
{"title":"Dynamic regulation of ROS stress in the accumulation of L-lysine in Escherichia coli","authors":"Li Zhang, Jianan Yang, Zhixuan Lv, Longjun Han, Zhiwei Zha, Zhijie Cheng, Xu Yang, Zhengyang Xu, Lei Yang, Jian Gao","doi":"10.1016/j.jbiotec.2026.01.011","DOIUrl":"10.1016/j.jbiotec.2026.01.011","url":null,"abstract":"<div><div>Oxidative stress in <em>Escherichia coli</em> during chemical production, caused by reactive oxygen species (ROS), impairs cell viability and limits output. This study addressed product accumulation and ROS stress in <span>L</span>-lysine-producing strains. Genetic engineering created three variants: dynamically up-regulated R1, down-regulated R2, and temporally regulatable R3 to reduce ROS during fermentation. Under stress conditions, all engineered strains showed significantly lower ROS levels versus parental strain R0, with R3 exhibiting the greatest reduction. Fermentation confirmed R3's superior performance, yielding 85.8 % more <span>L</span>-lysine than R0. These results demonstrate that constructing ROS mitigator achieves precise ROS control and efficient <span>L</span>-lysine synthesis. This dynamic regulation strategy enhances cell viability and production performance under oxidative stress, providing a viable approach for improving engineered cell factories' stress resistance.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"411 ","pages":"Pages 66-77"},"PeriodicalIF":3.9,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146052160","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}
Streptomyces-derived melanins exhibit diverse bioactive properties. This study aims to (1) produce melanin production from Streptomyces bottropensis SY8 (GenBank accesion number: PQ565816), (2) characterize the melanin, and (3) investigate its bioactive properties (toxicity and irritancy as well as invitro wound healing and anti-skin aging activities). Under optimized culture conditions, melanin production of 3.26 g/L was achieved in shaking flask cultures of the bacterium. The purified melanin was characterized as eumelanin. Compared to the control (Vitamin C), the purified melanin was found to have moderate antioxidant activity in radical scavenging assays. It did not cause toxicity on fibroblast cell line and irritancy in HET-CAM test (hen's egg test on chorioallantoic membrane test). The melanin reduced reactive oxygen species (ROS) accumulation and cell senescence induced by H2O2 or UV in fibroblast cells, indicating its anti-skin aging potential. When compared the control (melanin free), the melanin doses of 500 µg/mL and 1000 µg/mL caused increments of 17.59 % and 24.53 % in wound closure ratios at the end of the 24th hour, respectively. This is the first report on melanin production from S. bottropensis. Besides, in vitro wound healing and anti-skin aging activities of Streptomyces-derived melanins were investigated for the first time. Furthermore, HET-CAM test was used for the first time to analyze irritancy property of melanins. The results of this study indicate that S. bottropensis SY8-derived eumelanin can be exploited as an ingredient of anti-aging creams or wound dressings.
{"title":"Streptomyces bottropensis SY8-derived eumelanin exhibits skin wound healing activity and prevents H2O2 or UV-induced skin aging","authors":"Sevval Yildirim , Buket Bakan , Meryem Doymus , Seydanur Elmas , Nazli Pinar Arslan , Mesut Taskin","doi":"10.1016/j.jbiotec.2026.01.009","DOIUrl":"10.1016/j.jbiotec.2026.01.009","url":null,"abstract":"<div><div><em>Streptomyces</em>-derived melanins exhibit diverse bioactive properties. This study aims to (1) produce melanin production from <em>Streptomyces bottropensis</em> SY8 (GenBank accesion number: PQ565816), (2) characterize the melanin, and (3) investigate its bioactive properties (toxicity and irritancy as well as <em>invitro</em> wound healing and anti-skin aging activities). Under optimized culture conditions, melanin production of 3.26 g/L was achieved in shaking flask cultures of the bacterium. The purified melanin was characterized as eumelanin. Compared to the control (Vitamin C), the purified melanin was found to have moderate antioxidant activity in radical scavenging assays. It did not cause toxicity on fibroblast cell line and irritancy in HET-CAM test (hen's egg test on chorioallantoic membrane test). The melanin reduced reactive oxygen species (ROS) accumulation and cell senescence induced by H<sub>2</sub>O<sub>2</sub> or UV in fibroblast cells, indicating its anti-skin aging potential. When compared the control (melanin free), the melanin doses of 500 µg/mL and 1000 µg/mL caused increments of 17.59 % and 24.53 % in wound closure ratios at the end of the 24th hour, respectively. This is the first report on melanin production from <em>S. bottropensis</em>. Besides, <em>in vitro</em> wound healing and anti-skin aging activities of <em>Streptomyces</em>-derived melanins were investigated for the first time. Furthermore, HET-CAM test was used for the first time to analyze irritancy property of melanins. The results of this study indicate that <em>S. bottropensis</em> SY8-derived eumelanin can be exploited as an ingredient of anti-aging creams or wound dressings.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"411 ","pages":"Pages 40-53"},"PeriodicalIF":3.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146036093","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}
Pub Date : 2026-01-21DOI: 10.1016/j.jbiotec.2026.01.008
Priya S.A., Nevaditha N.T.
Poly(lactic acid) (PLA) composites reinforced with various natural fibers have been extensively investigated for biomedical applications. However, the use of nut grass-derived cellulose nanofibers (CNFs) remains unexplored in the current literature. This study presents the development of PLA nanocomposites reinforced with CNFs extracted from nut grass for biomedical applications. The PLA matrix was chemically modified using ethylene glycol dimethacrylate (EGDMA) and plasticized with castor oil. SEM analysis revealed uniform dispersion of CNFs at lower concentrations, leading to improved film morphology. XRD analysis indicated a CNF particle size of approximately 26 nm. Mechanical testing showed significant enhancements in material strength, with tensile strength and Young’s modulus increasing by 97.1 % and 113.9 %, respectively. The nanocomposites showed greater degradation in alkaline than acidic medium due to accelerated hydrolysis. Antibacterial activity against Staphylococcus aureus and Pseudomonas aeruginosa increased with CNF content. Hemolysis assays revealed reduced red blood cell damage compared to plain PLA, indicating favorable hemocompatibility. Additionally, MTT assay confirmed low cytotoxicity of the nanocomposites toward PBMC cells. These results demonstrate the potential of PLA nanocomposites as biocompatible, multifunctional materials suitable for applications in implants, wound healing and regenerative medicine.
{"title":"Antibacterial nut grass cellulose reinforced polylactic acid nanocomposites: A holistic assessment for biomedical scaffolds","authors":"Priya S.A., Nevaditha N.T.","doi":"10.1016/j.jbiotec.2026.01.008","DOIUrl":"10.1016/j.jbiotec.2026.01.008","url":null,"abstract":"<div><div>Poly(lactic acid) (PLA) composites reinforced with various natural fibers have been extensively investigated for biomedical applications. However, the use of nut grass-derived cellulose nanofibers (CNFs) remains unexplored in the current literature. This study presents the development of PLA nanocomposites reinforced with CNFs extracted from nut grass for biomedical applications. The PLA matrix was chemically modified using ethylene glycol dimethacrylate (EGDMA) and plasticized with castor oil. SEM analysis revealed uniform dispersion of CNFs at lower concentrations, leading to improved film morphology. XRD analysis indicated a CNF particle size of approximately 26 nm. Mechanical testing showed significant enhancements in material strength, with tensile strength and Young’s modulus increasing by 97.1 % and 113.9 %, respectively. The nanocomposites showed greater degradation in alkaline than acidic medium due to accelerated hydrolysis. Antibacterial activity against <em>Staphylococcus aureus</em> and <em>Pseudomonas aeruginosa</em> increased with CNF content. Hemolysis assays revealed reduced red blood cell damage compared to plain PLA, indicating favorable hemocompatibility. Additionally, MTT assay confirmed low cytotoxicity of the nanocomposites toward PBMC cells. These results demonstrate the potential of PLA nanocomposites as biocompatible, multifunctional materials suitable for applications in implants, wound healing and regenerative medicine.</div></div>","PeriodicalId":15153,"journal":{"name":"Journal of biotechnology","volume":"411 ","pages":"Pages 54-65"},"PeriodicalIF":3.9,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040224","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}
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