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Applications of Hyaluronic Acid in Pharmaceuticals, Healthcare and Cosmetics and Its Biosynthesis 透明质酸在医药、保健和化妆品中的应用及其生物合成。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-21 DOI: 10.1002/biot.70180
Seyedali Mousavi, Divakar Dahiya, Poonam Singh Nigam, Alina Sionkowska

Hyaluronic acid (HA) is an important homopolysaccharide also known as a natural anionic mucopolysaccharide or glycosaminoglycan formed by the alternate connection of glucuronic acid and N-acetylglucosamine as disaccharide units. For this review, the literature was searched in PubMed, Scopus, and Web of Science, using a few specific keywords including hyaluronic acid, biopolymer, glucuronic acid, N-acetylglucosamine, cosmetic, pharmaceutical, anti-aging and wound. Among the searched publications, further screening was done to select reports on the use of HA in healthcare and pharmaceutical products. Information relevant to the topic of this review has been presented in the article using 100 selected references, in eight tables and five figures. HA is a commercially valuable biocompatible polymer, which has been traditionally derived from rooster combs and animal tissues. However, it is currently produced through microbial fermentation by group C Streptococci. This biopolymer occurs naturally in several human tissues, including the skin and eyes. HA is a vital ingredient used in numerous products by global industries due to its unique characteristics, like inherent biocompatibility, tissue regenerative capacity, and anti-inflammatory properties. There has been a significant interest in recent years, enhanced across the pharmaceutical and cosmetic industries. Equally, the increased consumer interest from the aging population is compelling the demand for anti-aging products. Therefore, the global market for products formulated with HA marketed with defined benefits is experiencing significant growth. In this review, we have summarized current commercial applications of HA in many industries and consequently the increasing market size in specific application sectors in the next five years by 2030 in the international market.

透明质酸(HA)是一种重要的同质多糖,也被称为天然阴离子粘多糖或糖胺聚糖,由葡萄糖醛酸和n -乙酰氨基葡萄糖作为双糖单位交替连接而成。在PubMed、Scopus和Web of Science中检索相关文献,检索关键词包括透明质酸、生物聚合物、葡萄糖醛酸、n -乙酰氨基葡萄糖、化妆品、制药、抗衰老和伤口。在检索的刊物中,我们进一步筛选有关在保健及药剂产品中使用医管局的报告。与本综述主题相关的信息已在文章中使用100个选定的参考文献,以8个表格和5个数字的形式呈现。透明质酸是一种具有商业价值的生物相容性聚合物,传统上是从鸡冠和动物组织中提取的。然而,它目前是通过C群链球菌的微生物发酵生产的。这种生物聚合物自然存在于几种人体组织中,包括皮肤和眼睛。透明质酸因其独特的特性,如固有的生物相容性、组织再生能力和抗炎特性,是全球众多产品中使用的重要成分。近年来,制药和化妆品行业对其产生了浓厚的兴趣。同样,老龄化人口对消费者兴趣的增加也推动了对抗衰老产品的需求。因此,全球市场上以透明质酸配制的产品具有明确的效益,正在经历显着增长。在这篇综述中,我们总结了目前HA在许多行业的商业应用,以及到2030年在国际市场上特定应用领域的市场规模在未来五年的增长。
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引用次数: 0
Mechanisms and Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles as Nanocarriers in Musculoskeletal Disorders 干细胞来源的细胞外囊泡作为纳米载体在肌肉骨骼疾病中的作用机制和治疗潜力。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-15 DOI: 10.1002/biot.70172
Mengran Qin, Guang Li, Yan Wang, Zihan Wang, Youyi Liu, Hui Zhang, Benchao Dong, Peichuan Yang, Yong Wang, Jianxiong Ma

The musculoskeletal system consists of bones, joint cartilage, tendons, ligaments, muscles, and their associated nerves and blood vessels. These components work together to maintain human movement and mechanical stability, serving as the critical foundation for sustaining life activities. In recent years, with the acceleration of population aging, the incidence of musculoskeletal-related diseases such as sarcopenia, muscle atrophy, osteoporosis (OP), osteoarthritis (OA), and tendon injuries has continued to rise, significantly impacting patients’ quality of life and imposing a heavy social health burden. Mesenchymal stem cells (MSCs) have garnered widespread attention in tissue repair and regenerative medicine due to their excellent self-renewal capacity, multipotent differentiation potential, and low immunogenicity. Numerous studies have shown that the therapeutic effects of MSCs primarily depend on their paracrine actions, particularly the extracellular vesicles (EVs) they secrete, which play a crucial role in regulating tissue homeostasis and repairing damage. MSC-derived EVs possess biological functions similar to those of their parent cells and lack immunogenicity and tumorigenic risks. As effective carriers of intercellular signaling, they can transport various bioactive substances (such as miRNAs, mRNAs, proteins, and lipids), demonstrating significant advantages in regulating cellular functions within the musculoskeletal system, promoting tissue regeneration, and alleviating inflammation. This paper provides a systematic review of the research progress of MSC-derived EVs in musculoskeletal system diseases, focusing on their mechanisms of action and application potential in sarcopenia, osteoporosis, degenerative joint cartilage diseases, and tendon repair, aiming to provide theoretical basis and new research directions for related basic research and clinical translation.

肌肉骨骼系统由骨骼、关节软骨、肌腱、韧带、肌肉及其相关的神经和血管组成。这些部件协同工作,维持人体运动和机械稳定性,是维持生命活动的关键基础。近年来,随着人口老龄化的加速,肌肉减少症、肌肉萎缩症、骨质疏松症、骨关节炎、肌腱损伤等肌肉骨骼相关疾病的发病率持续上升,严重影响了患者的生活质量,给社会健康造成了沉重的负担。间充质干细胞(MSCs)由于具有良好的自我更新能力、多能分化潜能和低免疫原性,在组织修复和再生医学领域受到广泛关注。大量研究表明,间充质干细胞的治疗作用主要取决于其旁分泌作用,特别是其分泌的细胞外囊泡(EVs)在调节组织稳态和修复损伤中起着至关重要的作用。msc衍生的ev具有与其亲本细胞相似的生物学功能,但缺乏免疫原性和致瘤性风险。作为细胞间信号的有效载体,它们可以运输多种生物活性物质(如mirna、mrna、蛋白质和脂质),在调节肌肉骨骼系统内的细胞功能、促进组织再生、减轻炎症等方面具有显著优势。本文系统综述了msc衍生ev在肌肉骨骼系统疾病中的研究进展,重点介绍了其在肌肉减少症、骨质疏松症、退行性关节软骨疾病、肌腱修复等方面的作用机制和应用潜力,旨在为相关基础研究和临床转化提供理论依据和新的研究方向。
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引用次数: 0
Engineering of High-Yield Recombinant Adeno-Associated Virus Producer Plasmids 高产重组腺相关病毒产生质粒的工程设计。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-14 DOI: 10.1002/biot.70179
Marco T. Radukic, Dinh To Le, Robert Freudenberg, Anne Hammann, Omar Hamdan, Claire Rothschild-Gronau, Raimund Hoffrogge, Susanne K. Golm, Rebecca C. Feiner, Kathrin E. Teschner, Kristian M. Müller

Recombinant adeno-associated virus (rAAV) production lags demand with respect to quality and quantity. We report insights from producer plasmid engineering aimed at increasing yield and homogeneity of rAAV vectors obtained by HEK-293 triple transfection. Miniaturized production and same-day quantification streamlined the investigation. We demonstrate that modifications of the AAV2 Rep gene cluster reduces titers of currently circulating packaging plasmids. Revertants to wild type yielded 116-fold higher titers of about 106 particles per cell and reduced mispackaging. Modifications of predicted Rep post-translational modification sites decreased the empty capsid titer burden. A 7 kbp minimal helper plasmid lacking L4 22k maintained production capability upon optimized Rep expression for AAV2 but not for AAV6 and AAV9. Knockout of the egress protein MAAP increased rAAV yield from the cell pellet for convenient lysate processing. Together, these findings highlight the importance and potential tradeoffs of designing producer plasmids to obtain high titer systems.

重组腺病毒相关病毒(rAAV)的生产在质量和数量上落后于需求。我们报告了生产者质粒工程的见解,旨在提高HEK-293三重转染获得的rAAV载体的产量和均匀性。小型化生产和当日量化简化了调查。我们证明AAV2 Rep基因簇的修饰降低了目前流通的包装质粒的滴度。野生型的复归物的滴度提高了116倍,约为每个细胞106个颗粒,并且减少了误包装。预测Rep翻译后修饰位点的修饰降低了空衣壳滴度负荷。缺乏L4 22k的7 kbp最小辅助质粒在优化后的Rep表达中对AAV2保持了生产能力,但对AAV6和AAV9则没有。敲除输出蛋白MAAP增加了细胞颗粒的rAAV产量,方便了裂解物的处理。总之,这些发现强调了设计生产者质粒以获得高滴度系统的重要性和潜在的权衡。
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引用次数: 0
Advanced Scaffold-Guided Stem Cell Therapies for Myocardial Regeneration: Integrating Biomaterials, Cell Engineering, and Smart Delivery Systems 先进支架引导的心肌再生干细胞疗法:整合生物材料、细胞工程和智能输送系统。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-10 DOI: 10.1002/biot.70174
Khadije Yousefi, Ali Zareian Jahromi, Rozhin Kasiri, Peyman Daneshi

Myocardial infarction remains a leading cause of mortality worldwide, primarily due to the limited regenerative capacity of adult cardiac tissue. Recent advances in regenerative medicine aim to address this limitation through stem cell therapies supported by bioengineered scaffolds and targeted delivery systems. This review highlights current progress in scaffold-guided cardiac regeneration, focusing on the therapeutic potential of embryonic, mesenchymal, induced pluripotent, and cardiac-resident stem cells. The integration of natural and synthetic biomaterials, including hydrogels, decellularized extracellular matrices, and smart polymers, is discussed in relation to cell survival, engraftment, and paracrine signaling. Moreover, we examine innovative delivery strategies, such as temperature-responsive cell sheets, injectable hydrogel systems, and 3D-printed constructs. Key challenges, including poor cell retention, immune rejection, and variability in scaffold performance, are addressed along with emerging solutions like bioresponsive materials and multimodal imaging for in vivo cell tracking. Finally, we propose translational perspectives to accelerate the clinical application of scaffold-assisted stem cell therapies for heart repair. Overall, this review synthesizes current advances and emerging technologies to provide a comprehensive roadmap for optimizing scaffold-based stem cell strategies in cardiac regeneration.

心肌梗死仍然是世界范围内死亡的主要原因,主要是由于成人心脏组织的再生能力有限。再生医学的最新进展旨在通过生物工程支架和靶向递送系统支持的干细胞治疗来解决这一限制。本文综述了目前支架引导心脏再生的进展,重点关注胚胎干细胞、间充质干细胞、诱导多能干细胞和心脏驻留干细胞的治疗潜力。天然和合成生物材料的整合,包括水凝胶、脱细胞细胞外基质和智能聚合物,讨论了与细胞存活、植入和旁分泌信号的关系。此外,我们还研究了创新的递送策略,如温度响应细胞片、可注射水凝胶系统和3d打印结构。关键的挑战,包括细胞保留不良、免疫排斥和支架性能的可变性,以及生物反应材料和用于体内细胞跟踪的多模态成像等新兴解决方案都得到了解决。最后,我们提出了翻译的观点来加速支架辅助干细胞治疗心脏修复的临床应用。总的来说,本文综合了当前的进展和新兴技术,为优化支架干细胞在心脏再生中的策略提供了一个全面的路线图。
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引用次数: 0
Computational Fluid Dynamic Analysis of Fluid Motion and Volumetric Gas–Liquid Mass Transfer in Agitated Platelet Concentrate Storage 搅拌血小板浓缩库中流体运动和体积气液传质的计算流体动力学分析。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-08 DOI: 10.1002/biot.70177
Dean Pym, Amanda J. Davies, Jessica O. Williams, Christine Saunders, Chloë E. George, Allan Mason-Jones, Philip E. James

Computational fluid dynamics (CFD) offers a powerful tool in characterizing the complex biophysical environment inducing by dynamic storage conditions, providing insights often beyond the reach of conventional experimental approaches. As our understanding of platelet (PLT) biology has advanced, increased attention has been directed toward mechanical stresses, attributing shear forces encountered during collection, processing, and storage to an acceleration decline in PLT concentrate (PC) quality. CFD simulations using the volume of fluid model were used to simulate PC storage under varying agitation frequencies. Key parameters assessed include fluid velocity, wall shear stress (WSS), and gas–liquid mass transfer. Agitation increased fluid velocity and WSS while preserving the temporal symmetry characteristic of sinusoidal motion. Enhanced oxygen transfer was observed in open-top containers; however, when accounting for the gas permeability of storage materials, oxygen availability was ultimately constrained by container permeability rather than fluid motion. These results highlight the dual role of agitation: promoting oxygen transfer while simultaneously introducing mechanical stress that may contribute to PLT storage lesions. Importantly, since oxygen supply is limited by container permeability, reducing agitation could minimize shear-induced PLT damage without compromising oxygenation. Future optimization strategies may involve modifying storage container geometry or permeability to further improve oxygen delivery during storage.

计算流体动力学(CFD)为描述由动态存储条件引起的复杂生物物理环境提供了强大的工具,提供了传统实验方法无法达到的见解。随着我们对血小板(PLT)生物学的深入了解,人们越来越关注机械应力,将收集、加工和储存过程中遇到的剪切力归因于血小板浓缩物(PC)质量的加速下降。采用流体体积模型对不同搅拌频率下的PC存储进行了CFD模拟。评估的关键参数包括流体速度、壁面剪切应力(WSS)和气液传质。搅拌增加了流体速度和WSS,同时保持了正弦运动的时间对称性。在开盖容器中观察到氧传递增强;然而,当考虑到储存材料的气体渗透性时,氧气的可用性最终受到容器渗透性而不是流体运动的限制。这些结果突出了搅拌的双重作用:促进氧转移,同时引入可能导致PLT储存病变的机械应力。重要的是,由于氧气供应受到容器渗透性的限制,减少搅拌可以最大限度地减少剪切引起的PLT损伤,同时不影响氧合。未来的优化策略可能包括修改存储容器的几何形状或渗透率,以进一步改善存储过程中的氧气输送。
{"title":"Computational Fluid Dynamic Analysis of Fluid Motion and Volumetric Gas–Liquid Mass Transfer in Agitated Platelet Concentrate Storage","authors":"Dean Pym,&nbsp;Amanda J. Davies,&nbsp;Jessica O. Williams,&nbsp;Christine Saunders,&nbsp;Chloë E. George,&nbsp;Allan Mason-Jones,&nbsp;Philip E. James","doi":"10.1002/biot.70177","DOIUrl":"10.1002/biot.70177","url":null,"abstract":"<div>\u0000 \u0000 <p>Computational fluid dynamics (CFD) offers a powerful tool in characterizing the complex biophysical environment inducing by dynamic storage conditions, providing insights often beyond the reach of conventional experimental approaches. As our understanding of platelet (PLT) biology has advanced, increased attention has been directed toward mechanical stresses, attributing shear forces encountered during collection, processing, and storage to an acceleration decline in PLT concentrate (PC) quality. CFD simulations using the volume of fluid model were used to simulate PC storage under varying agitation frequencies. Key parameters assessed include fluid velocity, wall shear stress (WSS), and gas–liquid mass transfer. Agitation increased fluid velocity and WSS while preserving the temporal symmetry characteristic of sinusoidal motion. Enhanced oxygen transfer was observed in open-top containers; however, when accounting for the gas permeability of storage materials, oxygen availability was ultimately constrained by container permeability rather than fluid motion. These results highlight the dual role of agitation: promoting oxygen transfer while simultaneously introducing mechanical stress that may contribute to PLT storage lesions. Importantly, since oxygen supply is limited by container permeability, reducing agitation could minimize shear-induced PLT damage without compromising oxygenation. Future optimization strategies may involve modifying storage container geometry or permeability to further improve oxygen delivery during storage.</p>\u0000 </div>","PeriodicalId":134,"journal":{"name":"Biotechnology Journal","volume":"21 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931573","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
Pioneer Factor FOXA1 Boosts CHO Cell Productivity 先锋因子FOXA1提高CHO细胞的生产力。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-08 DOI: 10.1002/biot.70171
Sienna P. Butterfield, Fay L. Saunders, Robert J. White

Industrial production of biologics commonly involves the integration of transgenes into the genomes of host cells, such as Chinese hamster ovary (CHO) cells. A major determinant of productivity is the epigenetic control of the transgene promoter, accessibility of which can decrease during production due to the spread of heterochromatin. Pioneer factors such as forkhead box A1 (FOXA1) can bind heterochromatin, increase its accessibility and facilitate transcription of target genes. We show that FOXA1 can bind the EF1α and CMV promoters, which are widely used in industry. Overexpressing FOXA1 in CHO-K1 or an industrially-relevant CHO-DG44 cell line raised production of monoclonal antibody encoded by transgenes transcribed from these promoters. Mechanistically, this response can be attributed to recruitment by FOXA1 of epigenetic modifiers and a chromatin remodeling complex, which reprogram the promoter to optimize transcription. In parallel, FOXA1 overexpression induces endogenous genes with beneficial effects on cell viability. This strategy significantly enhanced cell-specific productivity, demonstrating potential benefit in biomanufacturing.

生物制剂的工业生产通常涉及将转基因整合到宿主细胞的基因组中,例如中国仓鼠卵巢(CHO)细胞。生产力的一个主要决定因素是转基因启动子的表观遗传控制,由于异染色质的扩散,其可及性在生产过程中降低。叉头盒A1 (FOXA1)等先锋因子可以结合异染色质,增加其可及性,促进靶基因的转录。我们发现FOXA1可以结合工业上广泛使用的EF1α和CMV启动子。在CHO-K1或工业相关的CHO-DG44细胞系中过表达FOXA1可提高由这些启动子转录的转基因编码的单克隆抗体的产生。从机制上讲,这种反应可归因于FOXA1招募表观遗传修饰因子和染色质重塑复合体,该复合体重新编程启动子以优化转录。同时,FOXA1过表达诱导内源基因对细胞活力产生有益影响。这一策略显著提高了细胞特异性生产力,显示了生物制造的潜在效益。
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引用次数: 0
From Liposomes to Virosomes: Evolution of Phospholipid Nanocarriers in Drug Delivery 从脂质体到病毒体:药物传递中磷脂纳米载体的进化。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-08 DOI: 10.1002/biot.70178
Kateryna Mykhailivna Doroshenko, Oleksandr Ivanovych Shevchenko

Phospholipid-based nanocarriers are an adaptable and chemically tunable class of drug delivery systems that self-assemble into bilayered vesicles due to the amphiphilic nature of phospholipids. Phospholipid-based nanocarriers can encapsulate both hydrophilic and hydrophobic drugs through non-covalent interactions and modulation of lipid phase behavior. This review explores the molecular and supramolecular principles governing the formation, stability, and function of key phospholipid-derived nanocarriers, including liposomes, transferosomes, ethosomes, invasomes, phytosomes, pharmacosomes, and virosomes. The structural attributes—such as bilayer packing, surface charge, curvature elasticity, and membrane permeability—are critically evaluated for the impact of those structural parameters on optimizing drug loading, drug release, and bioavailability. For example, variations in bilayer packing affect the encapsulation efficiency and drug release profiles, while surface charge modulates cellular uptake and colloidal stability. Curvature elasticity plays a pivotal role in membrane fusion and drug release, and membrane permeability determines the rate at which drugs diffuse from the nanocarrier. Emerging multilamellar systems such as vesosomes and spongosomes are also discussed for their potential in site-specific, controlled drug release. Common fabrication techniques (e.g., thin-film hydration, ethanol injection, freeze–thaw, and microfluidics) and characterization methods (e.g., DLS, DSC, FTIR, and cryo-TEM) are reviewed. The translational landscape is assessed through clinically approved liposomal drugs, patent trends, and ongoing trials involving stimuli-responsive systems. Challenges related to colloidal stability, tumor penetration, immune interactions, and large-scale manufacturing are addressed. This review provides a chemistry-centered framework to guide the rational design and clinical development of phospholipid nanocarriers, particularly in cancer therapeutics.

基于磷脂的纳米载体是一种适应性强、化学可调的药物递送系统,由于磷脂的两亲性,它们可以自组装成双层囊泡。基于磷脂的纳米载体可以通过非共价相互作用和调节脂相行为来包裹亲水和疏水药物。本文综述了磷脂源性纳米载体的形成、稳定性和功能的分子和超分子原理,包括脂质体、转移体、质体、侵入体、磷脂质体、药物质体和病毒体。结构属性——如双层包装、表面电荷、曲率弹性和膜透性——被严格评估这些结构参数对优化药物负载、药物释放和生物利用度的影响。例如,双层包装的变化影响包封效率和药物释放谱,而表面电荷调节细胞摄取和胶体稳定性。曲率弹性在膜融合和药物释放中起着关键作用,膜的通透性决定了药物从纳米载体扩散的速度。新兴的多层系统,如囊体和海绵体,也讨论了它们在位点特异性,控制药物释放方面的潜力。综述了常用的制备技术(如薄膜水化、乙醇注射、冻融和微流体)和表征方法(如DLS、DSC、FTIR和冷冻透射电镜)。通过临床批准的脂质体药物、专利趋势和涉及刺激反应系统的正在进行的试验来评估转化前景。解决了胶体稳定性、肿瘤穿透、免疫相互作用和大规模生产相关的挑战。本文综述提供了一个以化学为中心的框架来指导磷脂纳米载体的合理设计和临床开发,特别是在癌症治疗中。
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引用次数: 0
Issue Information: Biotechnology Journal 1/2026 期刊信息:Biotechnology Journal 1/2026
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-04 DOI: 10.1002/biot.70176
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引用次数: 0
Enhanced Lincomycin Titer Through Knockout of GntR Family Regulator SLCG_2790 Combined With Fermentation Optimization in an Industrial Strain of Streptomyces lincolnensis L-427 敲除GntR家族调控因子SLCG_2790并优化林肯链霉菌L-427工业菌株发酵提高林可霉素效价
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-04 DOI: 10.1002/biot.70173
Yinxu Zhao, Feng Xu, Qinghai Shang, Feng Li, Zhenhua Yu, Xiwei Tian, Ju Chu

In this study, lincomycin A (Lin-A), a lincosamide antibiotic primarily synthesized by Streptomyces lincolnensis, was selected as a model to demonstrate a combined genetic regulation and process engineering strategy for production improvement. The GntR-family transcriptional regulator SLCG_2790 was identified as a negative modulator of Lin-A biosynthesis. Disruption of SLCG_2790 in the industrial strain S. lincolnensis L-427 led to enhanced Lin-A accumulation, accompanied by increased transcriptional levels of mycothiol and ergothioneine biosynthesis genes. Metabolic flux analysis revealed an 83.6% elevation in pentose phosphate pathway activity compared to the parental strain. Despite the observed reduction in mycelial growth resulting from SLCG_2790 deletion, fermentation performance was significantly improved through medium optimization using Plackett–Burman design, steepest ascent, and response surface methodology. The optimized conditions yielded a 38.1% increase in Lin-A production in shake-flask culture, along with an accelerated onset of physiological activity. In a 5-L bioreactor, the engineered strain achieved a maximum Lin-A titer of 3640.6 mg/L, representing a 101.4% improvement over the parental strain cultured in the original medium. These findings underscore the potential of transcriptional regulation coupled with rational process optimization to overcome metabolic constraints and enhance antibiotic production in actinomycetes.

本研究以林肯链霉菌(Streptomyces lincolnensis)合成的lincosamide抗生素lincomycin A (Lin-A)为模型,通过基因调控和工艺工程相结合的策略来提高产量。gntr家族转录调节因子SLCG_2790被鉴定为Lin-A生物合成的负调节因子。工业菌株林肯S. L-427中SLCG_2790的破坏导致Lin-A积累增加,同时真菌硫醇和麦角硫因生物合成基因的转录水平增加。代谢通量分析显示,与亲本菌株相比,戊糖磷酸途径活性提高了83.6%。尽管SLCG_2790缺失导致菌丝生长减少,但通过使用Plackett-Burman设计、最陡上升和响应面法对培养基进行优化,发酵性能显著提高。优化后的条件使摇瓶培养的Lin-A产量提高了38.1%,并加速了生理活性的开始。在5-L的生物反应器中,工程菌株的最高Lin-A滴度为3640.6 mg/L,比在原始培养基中培养的亲本菌株提高了101.4%。这些发现强调了转录调控与合理的过程优化相结合的潜力,以克服代谢限制并提高放线菌的抗生素生产。
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引用次数: 0
A Growth-Coupled Evolutionary Strategy Enhances Heme Biosynthesis in Saccharomyces cerevisiae 生长耦合进化策略促进酿酒酵母菌血红素生物合成。
IF 3.1 3区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS Pub Date : 2026-01-04 DOI: 10.1002/biot.70175
Seoyoon Bang, Eunbi Kim, Sehyeon Park, Pil Kim

Enhancing the nutritional and sensory qualities of microbial single-cell proteins (SCPs) requires strategies to increase heme content in edible microorganisms. We adapted the Growth-Acceleration Targeting Evolution (GATE) platform, initially developed in Corynebacterium glutamicum, for use in Saccharomyces cerevisiae. By engineering a plasmid that connects the heme-responsive CYC1 promoter to the growth-promoting PTH1 gene, we established a feedback loop that links intracellular heme levels to accelerated cell proliferation. After 100 h of continuous culture under growth-selective pressure, we cured out the plasmid to isolate an Evol-GATE strain. Compared to the parental type, Evol-GATE displayed a five-fold increase in intracellular heme, a slight reduction in biomass, and coordinated upregulation of the heme biosynthetic pathway. Transcriptome analysis confirmed increased expression of heme biosynthesis and associated respiratory genes in Evol-GATE. Whole-genome sequencing revealed only a small number of dispersed variants, and no residual plasmid sequences, supporting its classification as a non-GMO mutant. Our results demonstrate that GATE can effectively select yeast mutants with significantly improved heme productivity, providing a promising approach to develop non-GMO SCPs enriched in heme for next-generation meat analogues.

提高微生物单细胞蛋白(SCPs)的营养和感官品质需要提高食用微生物中血红素含量的策略。我们将最初在谷氨酸棒状杆菌中开发的生长加速靶向进化(GATE)平台用于酿酒酵母。通过设计一种质粒,将血红素反应性CYC1启动子与促进生长的PTH1基因连接起来,我们建立了一个反馈回路,将细胞内血红素水平与加速细胞增殖联系起来。在生长选择压力下连续培养100 h后,我们将质粒固化,分离出一株进化门菌株。与亲本型相比,evolo - gate表现出细胞内血红素增加5倍,生物量略有减少,血红素生物合成途径协同上调。转录组分析证实,进化门中血红素生物合成和相关呼吸基因的表达增加。全基因组测序仅发现少量分散的变体,没有残留的质粒序列,支持其归类为非转基因突变体。我们的研究结果表明,GATE可以有效地选择具有显著提高血红素产量的酵母突变体,为开发富含血红素的非转基因SCPs提供了一种有希望的方法,用于下一代肉类类似物。
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引用次数: 0
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