Biochemical Engineering Journal最新文献_第6页

Effects of electrolyte composition and applied voltage on methane generation and microbial community shifts in the electromethanogenesis system 电解液组成和外加电压对甲烷电生成系统中甲烷生成和微生物群落迁移的影响

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-28 DOI: 10.1016/j.bej.2025.110035

Lucky Caesar Direstiyani, Daisuke Inoue, Michihiko Ike

An electromethanogenesis (EM) system was successfully established using non-acclimated anaerobic digestion sludge as the inoculum. This study aimed to evaluate the EM performance by varying the electrolyte composition and the applied voltage. Alterations in the microbial community associated with CH₄ generation and bioelectrochemchemical performance were also investigated. The findings indicated that the use of organic-rich electrolyte with a low applied voltage of 0.15 V showed a positive correlation with enhanced CH₄ generation up to 59 % and a CH₄ yield of 223.13 mmol day⁻¹ m⁻² which was ten times higher than the operation using the same electrolyte with an applied voltage of 0.35 V. Microbial community analysis revealed a shift of dominant methanogens from Methanosaeta to Methanosarcina and Methanoculleus at the cathodic biofilms when operated with organic-rich electrolyte at low voltage of 0.15 V. The presence of electroactive bacteria, such as DMER64 and JGI-0000079-D21, and syntrophic bacteria, including Desulfovibrio and Petrimonas, suggested the development of syntrophic interactions that strengthen biofilm resilience and the overall performance of the EM system. The microbial interaction network also emphasized the significance of electrolyte composition and adequate applied voltage in shaping microbial biofilms for efficient CH₄ generation. The findings of this study accentuate the roles of sufficient electrolyte composition and low-voltage in enhancing the EM performance and corroborate the synergistic advantages of the EM system.

以未驯化的厌氧消化污泥为接种物，成功建立了电产甲烷（EM）系统。本研究旨在通过改变电解液成分和施加电压来评估电磁性能。微生物群落的变化与CH4的产生和生物电化学性能也进行了研究。结果表明，使用低电压为0.15 V的富有机电解液，CH4生成率可提高59 %，CH4产率为223.13 mmol day−1 m−2，比使用相同电压为0.35 V的电解液提高10倍。微生物群落分析表明，在0.15 V富有机物电解液作用下，阴极生物膜上优势产甲烷菌由Methanosaeta向Methanosarcina和Methanoculleus转变。电活性细菌（如DMER64和JGI-0000079-D21）和共生细菌（包括Desulfovibrio和Petrimonas）的存在表明，共生相互作用的发展增强了生物膜的弹性和EM系统的整体性能。微生物相互作用网络还强调了电解质组成和适当的施加电压在形成微生物生物膜以有效生成CH4方面的重要性。本研究的结果强调了充足的电解质成分和低电压对提高电磁性能的作用，并证实了电磁系统的协同优势。

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引用次数: 0

Hydrodynamic velocity and interfacial mass transfer dynamics in the rotating bed reactor: Application to enzymatically catalyzed biodiesel production 旋转床反应器中流体动力速度和界面传质动力学：在酶催化生物柴油生产中的应用

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-27 DOI: 10.1016/j.bej.2025.110029

Shuai Huang , Haoyuan Tan , Luxuan Sun , Meng Wang , Biqiang Chen

This study demonstrated the advantages of the rotating bed reactor (RBR) over the conventional turbine stirred tank reactor (TSTR) for enzymatically catalyzed biodiesel synthesis using D311-resin immobilized lipase. Integrating simulation and experimental analyses, the work revealed that the rotating bed generated significantly lower shear forces compared to the turbine stirred paddles, thereby preserving lipase integrity and enhancing reusability. Simulations identified tangential velocity—modulated by rotational speed and bed porosity—as the dominant factor governing hydrodynamic velocity and liquid-solid mass transfer coefficients. Experimental validation confirmed these findings: Under optimized conditions, the yield of the fatty acid methyl esters (FAMEs) decreased from 87.49 % to 60.33 % after continuous use of immobilized lipase for 48 cycles in the RBR. In contrast, TSTR systems exhibited accelerated activity loss (≤69.9 % retention after 9 cycles) and yield deterioration (60.3 %). By mitigating shear-induced lipase deactivation and optimizing mass transfer, RBR technology paired with D311-resin immobilized lipase offers a scalable, cost-effective strategy for industrial biodiesel production.

以d311 -树脂固定化脂肪酶为原料，研究了旋转床反应器（RBR）在催化合成生物柴油方面优于传统的涡轮搅拌槽反应器（TSTR）。结合仿真和实验分析，研究表明，与涡轮搅拌桨相比，旋转床产生的剪切力显着降低，从而保持了脂肪酶的完整性并提高了可重用性。模拟结果表明，由转速和床层孔隙度调制的切向速度是控制流体动力速度和液固传质系数的主要因素。实验验证了这些发现：在优化条件下，固定化脂肪酶在RBR中连续使用48个循环后，脂肪酸甲酯（FAMEs）的产率从87.49 %下降到60.33 %。相比之下，TSTR体系表现出加速的活性损失（9个循环后保留率≤69.9 %）和产量恶化（60.3 %）。通过减少剪切引起的脂肪酶失活和优化传质，RBR技术与d311树脂固定化脂肪酶相结合，为工业生物柴油生产提供了一种可扩展的、具有成本效益的策略。

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引用次数: 0

AntibodyPlus enzyme fusion protein cell line development using a novel multidimensional screening of productivity, purity, and specific activity AntibodyPlus酶融合蛋白细胞系的开发使用一种新的多维筛选的生产力，纯度和特异性活性

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-27 DOI: 10.1016/j.bej.2025.110030

Yanling Wang , Lei Ma , Wilburt Tam, Weibin Zheng, Dana Lee, Qinhong Yu, Lixin Feng

AntibodyPlus denotes engineered antibodies that incorporate an added functional module, such as an enzyme, cytokine, peptide, or small-molecule payload, to expand or enhance their biological activity beyond that of a conventional antibody. Among its formats, enzyme-fusion antibodies, coupling binding modules to enzymes, enable precise functions for enzyme replacement, prodrug activation, diagnostics, and cancer therapy. However, as a hard-to-express protein, challenges remain in maintaining enzyme integrity, activity, and proper bispecific assembly during its manufacture. Thus, for enzyme-fusion antibodies, optimizing transfection and clone selection strategies that consider both titer and enzymatic activity is key for manufacturing and clinical translation. In this study, a Leap-In transposon site-specific integration strategy was first introduced to the enzyme-fusion antibody CHO transfection and expression system, providing sufficient, high-quality clones for screening. Sequentially, a novel tailored multidimensional single-clone screening method was originally established and introduced for the expression of asymmetric enzyme-fused antibodies, achieving both high titer and high enzyme activity systematically. It enabled efficient identification of high-performing clones, achieving titers above 6 g/L and enzymatic specific activities over 1200 mU/mg through vector chain balancing, optimized screening strategies, and analytical validation such as CE-SDS, SEC-HPLC, and ELISA. This work establishes a robust and resource-efficient CLD workflow for enzyme-fusion antibodies, offering a significant advancement for the expression and development of complex, hard-to-express biologics.

AntibodyPlus是指加入了额外功能模块的工程抗体，如酶、细胞因子、肽或小分子有效载荷，以扩大或增强其生物活性，超过传统抗体。在其格式中，酶融合抗体，酶偶联结合模块，使酶替代，前药激活，诊断和癌症治疗的精确功能。然而，作为一种难以表达的蛋白质，在其制造过程中保持酶的完整性，活性和适当的双特异性组装仍然存在挑战。因此，对于酶融合抗体，考虑滴度和酶活性的优化转染和克隆选择策略是制造和临床翻译的关键。本研究首次将Leap-In转座子位点特异性整合策略引入酶融合抗体CHO转染和表达系统，为筛选提供了充足、高质量的克隆。随后，我们建立并引入了一种新的定制多维单克隆筛选方法，用于非对称酶融合抗体的表达，系统地实现了高效价和高酶活性。通过载体链平衡、优化筛选策略以及CE-SDS、SEC-HPLC和ELISA等分析验证，高效鉴定出高效克隆，滴度大于6 g/L，酶特异性活性大于1200 mU/mg。这项工作为酶融合抗体建立了一个强大的、资源高效的CLD工作流程，为复杂的、难以表达的生物制品的表达和开发提供了重大的进步。

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引用次数: 0

Investigating the role of covalent stapling and cavity filling in enzyme thermostability 探讨共价钉接和空腔填充在酶热稳定性中的作用

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-26 DOI: 10.1016/j.bej.2025.110026

Guojuan Yi , Zidan Liu , Linyu Luo , Zhiqiang Ding , Tolbert Osire , Mengfei Long , Yongmei Xie

The enhancement of enzyme thermostability is critical for industrial applications such as food processing, and covalent bond engineering, such as disulfide bond formation, has proven effective in achieving this goal. However, the relationship between disulfide bond engineering and internal cavity modulation remained unclear. In this study, we first optimized the thermostability and catalytic performance of pullulanase using computer-aided disulfide bond engineering. The double disulfide bond mutant S643C-E668C/R680C-H715C exhibited significant improvements in thermostability (T_m increased by 6℃, half-life at 70℃ extended by 1.64-fold) and catalytic efficiency (specific activity enhanced by 21.5 %). Molecular dynamics simulations revealed that disulfide bonds stabilized the enzyme structure by reducing conformational flexibility, increasing molecular compactness, and optimizing internal cavities. Building on these findings, we developed a covalent bond “stapling” strategy based on internal cavity engineering and applied it to ethyl carbamate (EC) hydrolase, incorporating both disulfide and non-natural thioether bonds. Specific mutants, such as M46C-K123C and I76C-L212TAG, significantly improved catalytic activity, ethanol tolerance, and thermostability. These enhancements were attributed to rigid connections formed by covalent bonds in critical regions, which mitigated local stress or conformational changes potentially induced by cavity-filling mutations. By elucidating the synergistic effects of disulfide bond engineering and cavity filling, this study provided a novel theoretical and practical foundation for designing industrial enzymes with superior thermostability.

增强酶的热稳定性对于食品加工等工业应用至关重要，而共价键工程，如二硫键的形成，已被证明是实现这一目标的有效方法。然而，二硫键工程与内腔调制之间的关系尚不清楚。在本研究中，我们首先利用计算机辅助二硫键工程对普鲁兰酶的热稳定性和催化性能进行了优化。双二硫键突变体s645c - e668c /R680C-H715C表现出显著的热稳定性（Tm提高6℃，70℃半衰期延长1.64倍）和催化效率（比活性提高21.5 %）。分子动力学模拟表明，二硫键通过降低构象柔韧性、增加分子致密性和优化内腔来稳定酶的结构。基于这些发现，我们开发了一种基于内腔工程的共价键“钉接”策略，并将其应用于氨基甲酸乙酯（EC）水解酶，结合了二硫键和非天然硫醚键。特异性突变体，如M46C-K123C和I76C-L212TAG，显著提高了催化活性、乙醇耐受性和热稳定性。这些增强归因于关键区域的共价键形成的刚性连接，这减轻了局部应力或可能由空腔填充突变引起的构象变化。通过阐明二硫键工程与空腔填充的协同作用，为设计具有优良热稳定性的工业酶提供了新的理论和实践基础。

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引用次数: 0

Optimizing ammonium supply strategies for mitigation of free ammonia inhibition in the mass cultivation of Limnospira fusiformis 优化铵供应策略以缓解梭形Limnospira fususiformis大规模养殖中游离氨抑制

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-26 DOI: 10.1016/j.bej.2025.110018

Haymanot Yenesew Sewunet , Anupreet Kaur Chowdhary , Yuanjun Xia , Mutsumi Sekine , Pranshu Bhatia , Ayirkm Adugna Woldie , Tatsuki Toda

Ammonium is abundant in agro-industrial effluents, providing a cost-effective and sustainable nitrogen source for cultivating the cyanobacterium Limnospira fusiformis. However, under high pH conditions, ammonium converts into free ammonia (NH₃), causing inhibition. Therefore, an optimal ammonium supply strategy is required. This study assessed L. fusiformis growth under intermittent, continuous, and nighttime ammonium supply methods across four nitrogen loading rates: 3.9, 5.8, 11.6, and 17.4 mg NH₄⁺-N L⁻¹ d⁻¹ . At a loading rate of 11.6 mg NH₄⁺-N L⁻¹ d⁻¹ , intermittent and continuous supply yielded higher productivities (0.22 and 0.20 g L⁻¹ d⁻¹, respectively) than the nighttime method (0.15 g L⁻¹ d⁻¹) (p < 0.05). Increasing the loading rate to 17.4 mg NH₄⁺-N L⁻¹ d⁻¹ resulted in elevated NH₃ concentrations, leading to growth inhibition and productivity declines to 0.09, 0.10, and 0.06 g L⁻¹ d⁻¹ under intermittent, continuous, and nighttime supply, respectively (p < 0.05). This study is the first to demonstrate that continuous or intermittent ammonium supply strategies can be effectively applied in the mass cultivation of L. fusiformis.

农业工业废水中含有丰富的铵，为培养梭状蓝藻提供了一种经济、可持续的氮源。然而，在高pH条件下，铵转化为游离氨（NH3），产生抑制作用。因此，需要一个最佳的铵供应策略。这项研究评估了断断式、连续式和夜间铵供应方式下梭状乳杆菌的生长情况，四种氮负荷率：3.9、5.8、11.6和17.4 mg NH₄+ -N L⁻¹ d⁻¹ 。加载速率为11.6 mg NH₄ ⁺- n L⁻¹ d⁻¹ ,间歇和连续供应产生了更高的生产力(0.22和0.20 g  L⁻¹d⁻¹,分别)比夜间的方法(0.15 g  L⁻¹d⁻¹)(p & lt; 0.05)。提高加载速率为17.4 mg NH₄⁺- n L⁻¹ d⁻¹ 导致NH₃浓度升高,导致抑制增长和生产率下降至0.09,0.10,和0.06 g  L⁻¹ d⁻¹ 在断断续续的,连续的,分别和夜间供应(p & lt; 0.05)。本研究首次证明了连续或间歇铵供应策略可以有效地应用于梭状螺旋藻的大规模种植。

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引用次数: 0

Generation of gene-protein-reaction association rules in genome scale metabolic models: Chronology, challenges, and future perspectives 基因组尺度代谢模型中基因-蛋白反应关联规则的产生：年表、挑战和未来展望

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-25 DOI: 10.1016/j.bej.2025.110017

Pınar Kocabaş

Genome-scale metabolic models (GEMs) are powerful tools for exploring the metabolic state of cells and interpreting complex biological data. A key component of these models is the gene-protein-reaction (GPR) association, which links genes to enzymatic reactions via Boolean logic to account for isozymes and protein complexes. The accuracy of GPRs, alongside the stoichiometric matrix, critically determines the predictive performance of GEMs. GPRs play a central role in constructing condition-specific, cell line, and disease models, and are widely used in gene essentiality analysis, expression profiling, and strain design. This review presents a historical overview of GPR construction in mammalian and yeast GEMs, summarizes the main tools, databases, and methods used for their generation and curation, and identifies current challenges and limitations. Finally, potential improvements in GPR generation frameworks to enhance their utility in systems biology and metabolic engineering applications are discussed.

基因组尺度代谢模型（GEMs）是探索细胞代谢状态和解释复杂生物学数据的有力工具。这些模型的一个关键组成部分是基因-蛋白质-反应（GPR）关联，它通过布尔逻辑将基因与酶促反应联系起来，以解释同工酶和蛋白质复合物。gpr的准确性与化学计量矩阵一起，关键地决定了GEMs的预测性能。GPRs在构建条件特异性、细胞系和疾病模型中起着核心作用，并广泛用于基因本质分析、表达谱和菌株设计。本文介绍了在哺乳动物和酵母gem中构建GPR的历史概况，总结了用于它们的生成和管理的主要工具，数据库和方法，并指出了当前的挑战和局限性。最后，讨论了GPR生成框架的潜在改进，以增强其在系统生物学和代谢工程应用中的效用。

引用次数: 0

Inferring microbe–disease association via higher-order weighted perturbation and dual-channel feature learning based on similarity matrix fusion 基于相似矩阵融合的高阶加权扰动和双通道特征学习推断微生物与疾病的关联

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-24 DOI: 10.1016/j.bej.2025.110015

Xiaoxin Du , Lisen Yang , Bo Wang , Guangda Zhang

A growing number of studies have demonstrated that many complex human diseases are closely associated with microbial communities. Therefore, identifying potential microbe-disease associations is of great significance for disease diagnosis, prognosis, and treatment. However, traditional biomedical experiments are often costly, time-consuming, and labor-intensive. To address these challenges, we propose a novel computational model (HWP-SMFDCFL), for microbe-disease association prediction. Specifically, we introduce a new similarity matrix fusion algorithm (SMF) to integrate microbe and disease similarities. Second, a high-order weighted perturbation (HWP) technique is designed to dynamically assign weights to associations of different orders, thereby fully capturing high-order relational information. On this basis, a dual-path matrix factorization (DPMF) method is employed to reconstruct both original and high-order association matrices and extract low-dimensional linear features. Furthermore, by integrating hypergraph convolution and multilayer perceptron into dual-channel feature learning module (DCFL), the model captures nonlinear relationships in the microbe-disease similarity network at multiple levels, thus enhancing feature representation. Finally, Deep neural network (DNN) combined with Heterogeneous Newton boosting machine (HNBoost) is used to make the final predictions. Experimental results demonstrate that the proposed model outperforms six state-of-the-art prediction methods. Ablation Experiments and case study further validate its effectiveness and reliability. HWP-SMFDCFL is publicly available at https://github.com/senliyang/HWP-SMFDCFL.

越来越多的研究表明，许多复杂的人类疾病与微生物群落密切相关。因此，确定潜在的微生物与疾病的关联对疾病的诊断、预后和治疗具有重要意义。然而，传统的生物医学实验往往是昂贵、耗时和劳动密集型的。为了解决这些挑战，我们提出了一种新的计算模型（HWP-SMFDCFL），用于微生物-疾病关联预测。具体来说，我们引入了一种新的相似矩阵融合算法（SMF）来整合微生物和疾病的相似度。其次，设计了一种高阶加权摄动（HWP）技术，为不同阶的关联动态分配权重，从而充分捕获高阶关系信息。在此基础上，采用双路径矩阵分解（DPMF）方法重构原始关联矩阵和高阶关联矩阵，提取低维线性特征。此外，通过将超图卷积和多层感知器集成到双通道特征学习模块（DCFL）中，该模型在多个层次上捕获微生物-疾病相似网络中的非线性关系，从而增强特征表征。最后，利用深度神经网络（DNN）结合异质牛顿增强机（HNBoost）进行最终预测。实验结果表明，该模型优于六种最先进的预测方法。烧蚀实验和实例研究进一步验证了该方法的有效性和可靠性。HWP-SMFDCFL可在https://github.com/senliyang/HWP-SMFDCFL公开获取。

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引用次数: 0

Divanillin synthesis from vanillin by horseradish peroxidase in consideration of mathematical model and morphology of product 从数学模型和产物形态的角度考虑，用辣根过氧化物酶由香兰素合成二万尼林

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-24 DOI: 10.1016/j.bej.2025.110016

Ikuya Teranishi, Shusuke Ito, Shintaro Morisada, Keisuke Ohto, Hidetaka Kawakita

Vanillin is one of the monomers originated from lignin. We have synthesized divanillin from vanillin as a precipitate using the enzymatic reaction of horseradish peroxidase (HRP), to examine the effects of the concentration of HRP and of the reaction medium on the reactivity of the substrate and the morphology of the product, divanillin. Mathematical modeling was used to analyze the effects of solvent-induced enzyme inactivation and substrate reactivity on substrate concentration. The amount of HRP on the reaction influenced the inactivation due to the reaction media. It was quantitatively shown that changing the concentration of methanol in the reaction medium increased the solvation to the substrate vanillin and increased the contact efficiency with HRP. SEM observation of the precipitates revealed that they were spherical and needle-like and varied with the reaction conditions. Divanillin is a substance with potential for subsequent effective utilization of biomass, and this research will lead to future applications of novel materials.

香兰素是源自木质素的单体之一。我们利用辣根过氧化物酶（HRP）的酶促反应，将香兰素作为沉淀物合成了万西林，考察了HRP浓度和反应介质对底物反应活性和产物万西林形态的影响。采用数学模型分析了溶剂诱导酶失活和底物反应性对底物浓度的影响。由于反应介质的不同，HRP的投加量会影响失活效果。定量结果表明，改变反应介质中甲醇的浓度可以提高对底物香兰素的溶剂化，提高与HRP的接触效率。对析出物的SEM观察表明，析出物呈针状球形，随反应条件的变化而变化。vananillin是一种具有后续有效利用生物质潜力的物质，该研究将导致未来新材料的应用。

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引用次数: 0

Rational engineering of Corynebacterium glutamicum for L-Glutamine biosynthesis 谷氨酰胺棒状杆菌生物合成l -谷氨酰胺的合理工程

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-23 DOI: 10.1016/j.bej.2025.110011

Ying-Tong Lin, Meng Chai, Qing-Hai Liu, Yu-Shu Ma, Xin-Yi Tao, Min Liu, Dong-Zhi Wei

L-Glutamine (L-Gln) was efficiently biosynthesized in Corynebacterium glutamicum using metabolic engineering strategies. Four C. glutamicum strains (ATCC 13032, ATCC 13809, s026, and s9114) were screened, and γ-glutamyl kinase was deleted using CRISPR/Cas12a system to redirect carbon flux, increasing L-Gln titer from 4.7 g/L to 5.3 g/L. Several glutamine synthetase (GS) were screened from different sources, and Saccharomyces cerevisiae-derived GS demonstrated to be with optimal activity. Combined with RBS optimization to enhance translational efficiency, L-Gln titer was increased to 14.62 g/L. Subsequently, a dual strategy of site-directed mutagenesis of GS and small RNA-mediated inhibition of adenylyltransferase were conducted to relieve the adenylylation of GS, increasing L-Gln titer to 19.06 g/L. A “pull-push” strategy was implemented by strengthening glutamate dehydrogenase to enhance L-glutamate precursor supply while blocking L-Gln catabolism via deletion of glutamate synthase and glutaminase, resulting in 28.51 g/L L-Gln. Self-regulatory metabolic control was achieved using a growth-responsive promoter Pcg2705 to downregulate α-ketoglutarate dehydrogenase during stationary phase, achieving a shake flask titer of 31.85 g/L. The engineered strain CG17 produced 58.96 g/L L-Gln in a 5 L fed-batch bioreactor, with a yield of 0.31 g/g glucose and productivity of 1.05 g/L/h. The work provides valuable insights for developing high-performance strains for amino acid biosynthesis.

利用代谢工程技术在谷氨酰胺棒状杆菌中高效合成l -谷氨酰胺。筛选4株C. glutamum菌株ATCC 13032、ATCC 13809、s026和s9114，利用CRISPR/Cas12a系统删除γ-谷氨酰激酶，重定向碳通量，将L- gln滴度从4.7 g/L提高到5.3 g/L。从不同来源筛选了几种谷氨酰胺合成酶，结果表明，酿酒酵母衍生的谷氨酰胺合成酶活性最佳。结合RBS优化提高翻译效率，L- gln滴度提高到14.62 g/L。随后，通过对GS进行定点诱变和小rna介导的腺苷酸转移酶抑制的双重策略来缓解GS的腺苷酸化，将L- gln滴度提高到19.06 g/L。通过加强谷氨酸脱氢酶来增加L-谷氨酸前体供应，同时通过缺失谷氨酸合酶和谷氨酰胺酶来阻断L- gln分解代谢，实现“拉推”策略，使L- gln达到28.51 g/L。利用生长响应启动子Pcg2705在固定期下调α-酮戊二酸脱氢酶，实现自我调节代谢控制，摇瓶滴度为31.85 g/L。工程菌株CG17在5 L补料间歇反应器中产生58.96 g/L L- gln，产糖量为0.31 g/g，产率为1.05 g/L/h。这项工作为开发高效氨基酸生物合成菌株提供了有价值的见解。

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引用次数: 0

DLF-BBP: A novel deep learning framework for blood-brain barrier penetrating peptides design DLF-BBP：一种新的血脑屏障穿透肽设计深度学习框架

IF 3.7 3区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biochemical Engineering Journal

Pub Date : 2025-11-22 DOI: 10.1016/j.bej.2025.110014

Lei Huang , Zhanglong Li , Zhengtai Li , Hongjiang Li , Tiejun Bing , Yingji Li , Changyuan Yu

The blood-brain barrier (BBB) maintains brain homeostasis by selectively regulating substance exchange but also limits central nervous system (CNS) drug delivery. Blood-brain barrier penetrating peptides (BBPs) are short peptides capable of traversing the BBB, serving as drug carriers or therapeutic agents. Therefore, designing novel BBPs is crucial for overcoming the BBB's limitations and advancing CNS-targeted drug development. In this study, we propose a novel deep learning framework for BBPs design (DLF-BBP). Beginning with a Self-Attention Generative Adversarial Network (SAGAN) model to generate novel candidate BBPs that were evaluated in silico, we subsequently constructed a predictive model based on a Convolutional Neural Network (CNN) for the initial screening of GAN-designed BBPs, achieving an area under the curve (AUC) of 0.988 and an accuracy of 0.954. Further multi-step screening was conducted using physicochemical property analysis, molecular docking, and online platforms. Finally, the filtered candidate GAN-designed BBPs were validated through in vitro BBB penetration assay, leading to the identification of three promising GAN-designed BBPs with high permeation capability, demonstrating penetration comparable to that of the positive control Lixisenatide. Our research offers new possibilities for treating neurological disorders.

血脑屏障（BBB）通过选择性调节物质交换来维持大脑稳态，但也限制了中枢神经系统（CNS）的药物传递。血脑屏障穿透肽（BBPs）是一种能够穿过血脑屏障的短肽，可作为药物载体或治疗剂。因此，设计新的血脑屏障对于克服血脑屏障的局限性和推进cns靶向药物的开发至关重要。在本研究中，我们提出了一种新的bbp设计深度学习框架（DLF-BBP）。我们首先使用自注意生成对抗网络（Self-Attention Generative Adversarial Network， SAGAN）模型来生成新的候选bbp，并在计算机上进行评估，随后构建了基于卷积神经网络（Convolutional Neural Network， CNN）的预测模型，用于gan设计的bbp的初始筛选，实现了曲线下面积（AUC）为0.988，准确率为0.954。通过理化性质分析、分子对接和在线平台进行进一步的多步骤筛选。最后，通过体外血脑屏障渗透实验对过滤后的候选gan设计的血脑屏障进行验证，鉴定出三种具有高渗透能力的gan设计的血脑屏障屏障，其渗透能力与阳性对照利昔那肽相当。我们的研究为治疗神经系统疾病提供了新的可能性。

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