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Engineering strategies for microbial synthesis, customized modification, and application of hemoglobin 血红蛋白的微生物合成、定制修饰和应用的工程策略
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-14 DOI: 10.1016/j.biotechadv.2025.108752
Fan Liu , Chunxiang Feng , Zirui Yin , Jingwen Zhou , Jianghua Li , Jian Chen , Guocheng Du , Xinrui Zhao
Hemoglobin is a functional protein with heme as a cofactor, playing a crucial role in transporting oxygen and maintaining nitric oxide metabolic balance. Besides its physiological functions, hemoglobin has broad potential applications in medicine and biotechnology. However, the widespread use of hemoglobin is constrained by limited natural sources, challenges in heterologous synthesis, and functional restrictions that hinder efficient application. In this review, we discuss the key challenges and solutions associated with microbial synthesis of hemoglobin. We systematically elucidate the engineering strategies to improve the stability, autoxidation rate, heme-binding capacity, oxygen transport efficiency, and nitric oxide scavenging rate of hemoglobin, with particular emphasis on the use of artificial intelligence algorithms to customize the function modification of hemoglobin. Also, we provide a comprehensive overview of the various applications of hemoglobin, including artificial oxygen carriers, medical treatments requiring enhanced oxygen supply, synthesis of high-value products, biocatalysis, artificial foods, agriculture, functional substance testing, and bioactive peptide production, with a special focus on the potential of hemoglobin mutants and derivatives in expanding its use across various fields. Finally, we explore the prospects for accelerating the resolution of hemoglobin synthesis and overcoming the application challenges by integrating Pareto-optimal and iterative bioengineering frameworks, deep learning, synthetic biology, and other advanced technologies.
血红蛋白是一种以血红素为辅因子的功能性蛋白,在运氧和维持一氧化氮代谢平衡中起着至关重要的作用。除了具有生理功能外,血红蛋白在医学和生物技术方面具有广泛的应用前景。然而,血红蛋白的广泛使用受到有限的天然来源、异种合成的挑战以及阻碍有效应用的功能限制的限制。在这篇综述中,我们讨论了与微生物合成血红蛋白相关的主要挑战和解决方案。我们系统地阐明了提高血红蛋白稳定性、自氧化率、血红素结合能力、氧运输效率和一氧化氮清除率的工程策略,特别强调了使用人工智能算法来定制血红蛋白的功能修饰。此外,我们还全面概述了血红蛋白的各种应用,包括人工氧载体、需要增强氧气供应的医疗、高价值产品的合成、生物催化、人工食品、农业、功能物质检测和生物活性肽的生产,并特别关注血红蛋白突变体和衍生物在各个领域扩大其应用的潜力。最后,我们探讨了通过整合帕累托最优和迭代生物工程框架、深度学习、合成生物学和其他先进技术来加速血红蛋白合成和克服应用挑战的前景。
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引用次数: 0
Optimizing single and cascade microbial enzyme systems through site-directed mutagenesis for enhancing mycotoxin detoxification 优化单级和级联微生物酶系统通过定点诱变增强霉菌毒素解毒
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-10 DOI: 10.1016/j.biotechadv.2025.108751
Tosin Victor Adegoke , Sifan Lu , Ogedegbe Gloria Adegoke , Yufei Wang , Yan Wang
Mycotoxins, among the most extensively studied biological toxins, pose significant health risks to humans and animals, causing substantial economic losses in the agricultural sector. Numerous conventional enzymes isolated from microorganisms have been reported to detoxify mycotoxin, but their stability is questionable for detoxifying mycotoxin and the direct industrial production of enzymes. Currently, few commercial enzymes are available for the detoxification of mycotoxins. Enhancing enzyme stability is essential to ensure effective detoxification under feed-appropriate temperature and pH conditions. To overcome this challenge, the amalgamation of numerous fields, such as bioinformatics and protein engineering, is crucial for improving the enzyme for industrial production. Computational tools are crucial for determining the nucleotides of the sequence for modification using site-directed mutagenesis (SDM) for the existing conventional enzyme. The SDM technique offers a promising approach for modifying conventional enzymes for commercial purposes. Therefore, focusing on identifying, modifying, and producing enzymes that effectively detoxify mycotoxins is crucial for mitigating their effects on animals and preventing economic losses. Also, a fusion of modified enzymes involved in the cascade detoxification of mycotoxin and its derivatives should be focused on. This review provides an overview of the computational tools and protein engineering approaches, focusing on SDM and cascade catalysis for enhanced mycotoxin detoxification. We also discuss the future directions for incorporating these engineered enzyme systems on a commercial scale.
真菌毒素是研究最广泛的生物毒素之一,对人类和动物的健康构成重大风险,给农业部门造成重大经济损失。据报道,从微生物中分离出的许多常规酶可以解毒霉菌毒素,但它们在解毒霉菌毒素和直接工业生产酶方面的稳定性值得怀疑。目前,很少有商业酶可用于真菌毒素的解毒。提高酶的稳定性对于确保在适宜饲料的温度和pH条件下有效解毒至关重要。为了克服这一挑战,生物信息学和蛋白质工程等众多领域的融合对于提高酶的工业生产至关重要。计算工具对于确定现有常规酶的位点定向突变(SDM)修饰序列的核苷酸至关重要。SDM技术为用于商业目的的传统酶的修饰提供了一种很有前途的方法。因此,专注于鉴定、改造和生产能够有效解毒真菌毒素的酶对于减轻其对动物的影响和防止经济损失至关重要。此外,参与真菌毒素及其衍生物级联解毒的修饰酶的融合应该是重点。这篇综述综述了计算工具和蛋白质工程方法,重点是SDM和级联催化增强霉菌毒素解毒。我们还讨论了在商业规模上整合这些工程酶系统的未来方向。
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引用次数: 0
Methods for detecting off-target effects of CRISPR/Cas9 CRISPR/Cas9脱靶效应检测方法
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-08 DOI: 10.1016/j.biotechadv.2025.108750
Ying-ying Xu , Sheng-mei Zhou , Lu-yan Wang , Rong Zhang , Kai Li , Zhi-yuan Qian , Li Xiao
The CRISPR/Cas9 system has emerged as a revolutionary tool for gene editing, widely used in the biomedical field due to its simplicity, efficiency, and cost-effectiveness. However, evidence suggests that CRISPR/Cas9 can induce off-target effects, leading to unintended mutations that may compromise the precision of gene modifications. Consequently, predicting,detecting and evaluating these off-target effects is crucial for optimizing the accuracy and reliability of CRISPR/Cas9 system. This paper provides an overview of the various methodologies and strategies, used or to be used for identifying off-target effects in CRISPR/Cas9-based genome editing, offering insights to improve the precision and safety of CRISPR applications in research and therapeutics.
CRISPR/Cas9系统已成为一种革命性的基因编辑工具,因其简单、高效和成本效益而广泛应用于生物医学领域。然而,有证据表明,CRISPR/Cas9可以诱导脱靶效应,导致可能损害基因修饰精度的意外突变。因此,预测、检测和评估这些脱靶效应对于优化CRISPR/Cas9系统的准确性和可靠性至关重要。本文概述了在基于CRISPR/ cas9的基因组编辑中用于或将用于识别脱靶效应的各种方法和策略,为提高CRISPR在研究和治疗中应用的准确性和安全性提供了见解。
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引用次数: 0
Precise control of transcriptional stoichiometry in bacteria: From mechanisms to synthetic biology applications 细菌转录化学计量学的精确控制:从机制到合成生物学应用
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-02 DOI: 10.1016/j.biotechadv.2025.108748
Duodong Wang , Na Wang , Houhui Song , Chenggang Xu
Bacteria exhibit remarkable precision in controlling the stoichiometry of protein subunits within metabolic pathways and macromolecular complexes—a requirement for optimal function and fitness. This review explores the RNA-level mechanisms that enable bacteria to maintain precise subunit ratios, moving beyond canonical transcriptional regulation to highlight the role of post-transcriptional fine-tuning. We discuss how internal transcriptional terminators serve as tunable attenuators, creating expression gradients within polycistronic operons, and how selective RNA processing and stabilization (SRPS) systems generate differential mRNA stability to shape proteomic stoichiometry. Furthermore, we outline how these native strategies have inspired the design of synthetic genetic circuits—including promoter libraries, engineered terminators, and RNase-based processing modules—that allow programmable control of gene expression levels. By leveraging modular and layered regulatory elements, synthetic biologists can now construct robust systems with user-defined stoichiometric outputs, facilitating the engineering of complex metabolic pathways and protein assemblies for biotechnological and biomedical applications.
细菌在控制代谢途径和大分子复合物中蛋白质亚基的化学计量学方面表现出非凡的精确性,这是最佳功能和适应性的要求。这篇综述探讨了rna水平的机制,使细菌能够保持精确的亚基比率,超越典型的转录调控,突出转录后微调的作用。我们讨论了内部转录终止子如何作为可调衰减子,在多顺反子操纵子内创建表达梯度,以及选择性RNA加工和稳定(SRPS)系统如何产生差异mRNA稳定性以形成蛋白质组学化学统计。此外,我们概述了这些天然策略如何启发合成遗传电路的设计-包括启动子库,工程终止子和基于rase的处理模块-允许对基因表达水平进行可编程控制。通过利用模块化和分层调节元件,合成生物学家现在可以构建具有用户定义的化学计量输出的强大系统,促进生物技术和生物医学应用的复杂代谢途径和蛋白质组装的工程。
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引用次数: 0
Peroxisome engineering in yeast: Advances, challenges, and prospects 酵母过氧化物酶体工程:进展、挑战和前景
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 DOI: 10.1016/j.biotechadv.2025.108747
Cuifang Ye , Xiaoqian Li , Tao Liu , Shiyu Li , Mengyu Zhang , Yao Zhao , Jintao Cheng , Guiling Yang , Peiwu Li
Peroxisome engineering in yeast has emerged as a promising strategy for biomanufacturing, as it enables the compartmentalization of biosynthetic pathways and thus alleviates key bottlenecks in natural product biosynthesis. By sequestering specific metabolic pathways within peroxisomes, this strategy effectively reduces product cytotoxicity, enhances intracellular product storage, and allows precise redirection of metabolic fluxes. Nevertheless, its broader application remains limited by several unresolved challenges, including the insufficient understanding of peroxisomal membrane permeability, inadequate cofactor supply, and glucose-mediated repression of peroxisomal capacity. To overcome these obstacles, a range of conventional and emerging approaches—such as engineering peroxisomal targeting signal type 1 (PTS1), regulation of peroxisome proliferation, development of orthogonal artificial peroxisomal protein transport systems, and applying machine learning to predict gene overexpression for optimizing peroxisomal functional capacity—have expanded the toolkit for peroxisome engineering in yeast. This review summarizes recent advances in peroxisomal surface display engineering, peroxisomal matrix engineering, and multi-organelle spatial combination coordination, highlighting the importance of peroxisome engineering in optimizing yeast-based cell factories for natural product biosynthesis. Moreover, it critically evaluates current limitations, along with a comprehensive discussion of both conventional and emerging approaches aimed at further optimizing peroxisome engineering. In the future, integrating peroxisome engineering with advanced machine learning will be crucial for addressing remaining challenges and fully realizing the potential of sustainable and scalable yeast-based biomanufacturing.
酵母中的过氧化物酶体工程已成为生物制造的一种有前途的策略,因为它使生物合成途径的区隔化成为可能,从而缓解了天然产物生物合成的关键瓶颈。通过在过氧化物酶体中隔离特定的代谢途径,这种策略有效地降低了产物的细胞毒性,增强了细胞内产物的储存,并允许代谢通量的精确重定向。然而,它的广泛应用仍然受到几个尚未解决的挑战的限制,包括对过氧化物酶体膜通透性的了解不足,辅因子供应不足,葡萄糖介导的过氧化物酶体容量抑制。为了克服这些障碍,一系列传统的和新兴的方法——如工程过氧化物酶体靶向信号类型1 (PTS1),调节过氧化物酶体增殖,正交人工过氧化物酶体蛋白质运输系统的发展,以及应用机器学习来预测基因过表达以优化过氧化物酶体的功能能力——扩大了酵母过氧化物酶体工程的工具箱。本文综述了近年来在过氧化物酶体表面显示工程、过氧化物酶体基质工程和多细胞器空间组合协调等方面的研究进展,强调了过氧化物酶体工程在优化酵母细胞工厂进行天然产物生物合成中的重要性。此外,它批判性地评估了当前的局限性,并全面讨论了旨在进一步优化过氧化物酶体工程的传统方法和新兴方法。在未来,将过氧化物酶体工程与先进的机器学习相结合将是解决剩余挑战和充分实现可持续和可扩展的酵母生物制造潜力的关键。
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引用次数: 0
Brews, fuels, and opioids: Expanding the yeast Ehrlich pathway for chemical and pharmaceutical manufacturing. 啤酒、燃料和阿片类药物:扩大酵母埃利希途径用于化学和制药制造。
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-08-06 DOI: 10.1016/j.biotechadv.2025.108684
Anastasia E C Rumpl, Joshua R Goodhew, Paul F Kelly, Mika Hirano, Michael E Pyne

The Ehrlich pathway is a catabolic process that imparts Saccharomyces cerevisiae and other yeasts with the ability to utilize branched-chain and aromatic amino acids as a source of nitrogen. Using this route, amino acids are transaminated to α-keto acids and the liberated ammonia is utilized for assimilatory reactions. This process leaves behind an array of aliphatic and aromatic carbon skeletons (fusel metabolites) that have found a multitude of uses in the production of flavors, chemicals, and pharmaceuticals. This review provides an update on the genetics and biochemistry of the Ehrlich pathway with an emphasis on the biotechnological valorization of fusel metabolites. We outline the impact of fusel metabolism on the organoleptic properties of fermented beverages and recap ongoing efforts to repurpose the Ehrlich pathway for production of advanced biofuels. We also highlight recent activity directed at producing opioids and other plant benzylisoquinolines, as well as engineering new-to-nature alkaloids by rewiring the yeast Ehrlich pathway. Collectively, these efforts have stimulated a deeper understanding of yeast fusel metabolism and opened new opportunities for biomanufacturing using conventional and non-conventional yeasts.

埃利希途径是一种分解代谢过程,赋予酿酒酵母和其他酵母利用支链氨基酸和芳香氨基酸作为氮源的能力。通过这种途径,氨基酸被转胺为α-酮酸,释放的氨被用于同化反应。这一过程留下了一系列脂肪族和芳香碳骨架(杂醇化代谢物),它们在香精、化学品和药品的生产中有着广泛的用途。这篇综述提供了埃利希途径的遗传学和生物化学方面的最新进展,重点是燃料代谢物的生物技术增值。我们概述了燃料代谢对发酵饮料的感官特性的影响,并概述了正在进行的重新利用埃利希途径生产先进生物燃料的努力。我们还强调了最近针对生产阿片类药物和其他植物苯基异喹啉的活动,以及通过重新连接酵母埃利希途径来设计新的自然生物碱。总的来说,这些努力刺激了对酵母燃料代谢的更深层次的理解,并为使用传统和非传统酵母的生物制造开辟了新的机会。
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引用次数: 0
Bacillus spore germination: Interpretation of the spore germination mechanism and innovation of the inactivation strategies. 芽孢杆菌孢子萌发:孢子萌发机制的阐释及灭活策略的创新。
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-08-06 DOI: 10.1016/j.biotechadv.2025.108683
Yangfu Li, Juan Wang, Guicheng Zhou, Xiaoming Yuan, Ling Chen, Qihui Gu, Youxiong Zhang, Xianhu Wei, Yu Ding, Qingping Wu

Bacillus is a ubiquitous genus renowned for its ability to form highly resilient spores, posing significant challenges to the food industry. As society progresses, the demand for high-quality food continues to rise. While reducing excessive processing helps maintain nutritional value and quality which fits the demands from consumers, it increases the risk of spore contamination. Germination-inactivation strategies offer a promising solution by converting spores into vegetative cells, which can be eliminated through milder treatments, thus preserving food quality while ensuring food safety. However, the limited efficiency of current methods to induce germination, particularly due to the emergence of super-dormant spores, hinders their widespread application. Optimizing spore germination is critical for the successful implementation of the germination-inactivation strategies. This study aims to provide a comprehensive overview of the mechanisms underlying Bacillus spore germination, focusing on the latest advances in signal transduction and macromolecular biosynthesis. Additionally, we systematically summarize the characteristics of super-dormant spores and their potential causes. Current methods for enhancing spore germination efficiency are thoroughly reviewed, and their limitations are discussed in detail. Based on these insights, innovative solutions are proposed to address the existing challenges. Recent research has unveiled the signal transduction mechanisms involved in spore germination, emphasizing the critical role of ion release. Moreover, transcription and translation likely govern dipicolinic acid release and cortex hydrolysis, respectively, with spores being able to rapidly initiate transcription through pre-located RNA polymerase. Interestingly, the emergence of super-dormant spores is influenced by both permanent and transient factors. To improve spore germination efficiency, promising solutions include innovative screening of germinants, optimization of the key factors of thermal activation and pressure-induced germination, and utilization of key substances during germination process.

芽孢杆菌是一种普遍存在的属,以其形成高度弹性孢子的能力而闻名,对食品工业构成了重大挑战。随着社会的进步,对高质量食品的需求不断增加。虽然减少过度加工有助于保持符合消费者需求的营养价值和质量,但它增加了孢子污染的风险。发芽灭活策略提供了一个很有前途的解决方案,通过将孢子转化为营养细胞,可以通过温和的处理消除,从而在确保食品安全的同时保持食品质量。然而,目前诱导发芽的方法效率有限,特别是由于超级休眠孢子的出现,阻碍了它们的广泛应用。优化孢子萌发是成功实施发芽灭活策略的关键。本文综述了芽孢杆菌孢子萌发的机制,重点介绍了信号转导和大分子生物合成的最新进展。此外,我们还系统地总结了超休眠孢子的特征及其潜在原因。综述了目前提高孢子萌发效率的方法,并详细讨论了它们的局限性。基于这些见解,提出了解决现有挑战的创新解决方案。近年来的研究揭示了孢子萌发的信号转导机制,强调了离子释放的关键作用。此外,转录和翻译可能分别控制着二吡啶酸的释放和皮质水解,孢子能够通过预先定位的RNA聚合酶快速启动转录。有趣的是,超级休眠孢子的出现受到永久和短暂因素的影响。为了提高孢子的萌发效率,有希望的解决方案包括创新筛选萌发剂,优化热激活和压力诱导萌发的关键因素,以及萌发过程中关键物质的利用。
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引用次数: 0
Dissecting the specificity of sugar code recognition - Unleashing the biomedical potential of galectins by protein engineering. 剖析糖编码识别的特异性——通过蛋白质工程释放凝集素的生物医学潜力。
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-11-01 Epub Date: 2025-08-05 DOI: 10.1016/j.biotechadv.2025.108681
Marta Kalka, Julia Ptak, Paulina Gregorczyk, Krzysztof Ciura, Aleksandra Chorążewska, Subhradeep Haldar, Natalia Porębska, Ewa Marcinkowska, Łukasz Opaliński

The cell surface is extremely rich in multilayered information that exists in the form of complex monosaccharide assemblies, establishing a cellular sugar code. The sugar code is specifically deciphered by extracellular lectins, galectins, which are capable of recognizing sugar code components and transforming the code into precise cellular activities. Galectin-dependent reading of the sugar code relies on two major features: the specific recognition of sugars by the galectins' carbohydrate recognition domains (CRDs) and the modular architecture of galectins or their oligomerization. These two characteristics of galectins are essential for most of galectins' functions, as they ensure the specificity of sugar code recognition and permit multivalent interactions with carbohydrate ligands. The natural galectins are characterized by relatively fixed modular architecture, which allows for evolutionarily defined reading of the sugar code, limiting the spectrum of biological activities of galectins. Distinct protein engineering approaches, like linker modulation, crosslinking, domain swapping or fusion with oligomerization scaffolds allow for the modulation of galectin multivalency in order to overcome the natural decoding limitations of galectins and permit alternative reading of the sugar code. In this review, we we provide an overview of the architectures of engineered galectins with altered valency and discuss how alternative reading of the code by such proteins may prove beneficial in biotechnology.

细胞表面含有极其丰富的多层信息,这些信息以复杂的单糖组合的形式存在,建立了细胞糖密码。细胞外凝集素(galectin)能够识别糖密码成分并将其转化为精确的细胞活动,从而特异地破译糖密码。半乳糖凝集素依赖性的糖编码读取依赖于两个主要特征:半乳糖凝集素的碳水化合物识别域(CRDs)对糖的特异性识别和半乳糖凝集素的模块化结构或其寡聚化。这两个特征对于大多数乳糖凝集素的功能至关重要,因为它们确保了糖编码识别的特异性,并允许与碳水化合物配体的多价相互作用。天然半乳糖凝集素具有相对固定的模块化结构,这允许从进化角度定义糖密码的读取,限制了半乳糖凝集素的生物活性谱。不同的蛋白质工程方法,如连接子调制、交联、结构域交换或与寡聚化支架的融合,允许调节聚集素的多价性,以克服聚集素的自然解码限制,并允许糖密码的替代读取。在这篇综述中,我们概述了具有改变价的工程聚集素的结构,并讨论了这些蛋白质对代码的替代读取如何在生物技术中证明是有益的。
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引用次数: 0
Advances in biosensors for microbial biosynthesis of amino acids and their derivatives 微生物合成氨基酸及其衍生物生物传感器研究进展
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-10-27 DOI: 10.1016/j.biotechadv.2025.108746
Huina Dong , Tingting Li , Xinyi Ren , Huiying Wang , Xuan Liu , Xuyang Huang , Xiaolin Shen , Gang Fu , Miaomiao Xia , Guangqing Du , Xinxiao Sun , Jia Wang , Zhaoxia Jin , Sang Yup Lee , Qipeng Yuan , Dawei Zhang
Amino acids and their derivatives play pivotal roles across diverse fields including biotechnology, pharmaceuticals, agriculture, and industrial manufacturing. The development of high-throughput screening methods for strains producing amino acids and their derivatives is crucial for both mining key enzymes and screening overproducers. This review systematically evaluates six classes of direct biosensors employed in the metabolic engineering of amino acid- or derivative-producing strains. These include biosensors based on transcription factors, riboswitches, Förster resonance energy transfer, circularly permuted fluorescent proteins, compound-inducible putative promoter regions, and protein translation elements. Their operational principles and recent advances in rational design, performance optimization, and practical implementation are critically analyzed. In addition, a systematic analysis of four categories of indirect biosensing strategies for the screening or regulation of amino acid- or derivative-producing strains is provided. These strategies target universal metabolic precursors, pathway-specific precursors, enzymatically transformed downstream metabolites, or competitive intermediates in branched pathways. Then, the design strategies, performance optimization methods, and practical implementation challenges of the existing biosensors are compared, which are accompanied by the discussion of the key parameters that are optimal for the biosensors applied in metabolic engineering. This work will facilitate the development of biosensors for metabolites that currently lack biosensing systems, and promote the innovation of the existing biosensors. These developments are expected to support efficient and sustainable production of amino acid-related compounds and other high-value metabolites.
氨基酸及其衍生物在生物技术、制药、农业和工业制造等领域发挥着关键作用。开发高通量筛选氨基酸及其衍生物菌株的方法对于挖掘关键酶和筛选过量生产者至关重要。本文系统地评价了六类用于氨基酸或衍生物生产菌株代谢工程的直接生物传感器。这些包括基于转录因子的生物传感器,核开关,Förster共振能量转移,循环排列的荧光蛋白,化合物诱导的假定启动子区域和蛋白质翻译元件。他们的工作原理和最近的进展,合理的设计,性能优化和实际实施进行了批判性的分析。此外,系统地分析了四类用于筛选或调节氨基酸或衍生物产生菌株的间接生物传感策略。这些策略针对普遍代谢前体、途径特异性前体、酶转化的下游代谢物或分支途径中的竞争中间体。然后,比较了现有生物传感器的设计策略、性能优化方法和实际实现挑战,并讨论了应用于代谢工程的生物传感器的最佳关键参数。这项工作将促进目前缺乏生物传感系统的代谢物生物传感器的发展,并促进现有生物传感器的创新。预计这些发展将支持氨基酸相关化合物和其他高价值代谢物的高效和可持续生产。
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引用次数: 0
Regulating cellular activity to enhance microbial cell factory efficiency 调节细胞活动,提高微生物细胞工厂效率
IF 12.5 1区 工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2025-10-24 DOI: 10.1016/j.biotechadv.2025.108745
Chong Qiu , Tianzhao Zhang , Guangjie Liang , Kaifang Liu , Jia Liu , Xiaomin Li , Guipeng Hu , Cong Gao , Liming Liu
Cellular activity serves as a critical determinant of growth, metabolism, and production efficiency in microbial cell factories. However, industrial-scale microbial fermentation is often limited by reduced cellular activity due to metabolite toxicity, metabolic burden, and environmental stress, which constrain productivity and compromise target compound synthesis. This review systematically explores contemporary strategies to enhance cellular activity, focusing on three aspects: (i) alleviating toxicity from substrates, intermediates, and products; (ii) optimizing cellular resource allocation and cofactor synthesis to reduce metabolic burden; and (iii) developing adaptive evolution techniques, screening tolerance targets, engineering cell membranes, and employing exogenous protective agents to bolster cell resistance to environmental stress. Recent advances addressing these challenges are summarized, aiming to enhance the production capacity and stability of microbial cell factories. Finally, we discuss persistent challenges and future research priorities in improving cellular activity.
在微生物细胞工厂中,细胞活性是生长、代谢和生产效率的关键决定因素。然而,工业规模的微生物发酵往往受到代谢物毒性、代谢负担和环境压力导致的细胞活性降低的限制,这些因素限制了生产率并损害了目标化合物的合成。本综述系统地探讨了增强细胞活性的当代策略,重点关注三个方面:(1)减轻底物、中间体和产物的毒性;(ii)优化细胞资源分配和辅因子合成,减轻代谢负担;(iii)发展适应性进化技术,筛选耐受性靶点,工程细胞膜,并使用外源性保护剂来增强细胞对环境胁迫的抵抗力。综述了近年来解决这些挑战的研究进展,旨在提高微生物细胞工厂的生产能力和稳定性。最后,我们讨论了改善细胞活性的持续挑战和未来的研究重点。
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引用次数: 0
期刊
Biotechnology advances
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