Biotechnology advances最新文献_第10页

Exploring the enzymatic landscape of 4-α-glucanotransferases in carbohydrate bioprocessing 探索碳水化合物生物加工中4-α-葡萄糖基转移酶的酶景观。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-14 DOI: 10.1016/j.biotechadv.2025.108737

Yu Wang , Yu Tian , Marie Sofie Møller , Zhengyu Jin , Xiaoxiao Li , Birte Svensson

4-α-Glucanotransferases (4αGTs), also known as amylomaltases or disproportionating enzymes, catalyze α-1,4-glucan and maltooligosaccharide transfer in starch and glycogen metabolism of microorganisms, plants and animals. The present review covers their classification, reactions, structure-function relationships, engineering and applications. 4αGTs belong to glycoside hydrolase families GH13, GH57, and GH77, and catalyze four types of reactions: disproportionation, cyclization, coupling, and hydrolysis, of which the first two are particularly important for biotechnological applications. Insights into active site structures and substrate binding have facilitated the rational design of product specificity, modes of action, and increased product yields. Assays of the four reactions encompass monitoring amylose consumption by iodine staining, release of glucose in maltotriose disproportionation, chromatographic analysis of change in chain lengths, and release of reducing sugar by hydrolysis. Major reactions in transglycosylation of starch include formation of amylopectin with extended branch chains and cyclization to large-ring cyclodextrins (LR-CDs), also referred to as cycloamyloses (CAs). Product yields, chain length distribution, and size of LR-CDs depend on the enzyme, substrates and reaction conditions. 4αGT products are useful in the food, biomaterials and pharma sectors. Thus, chain length modification can elicit resistance of starch to digestion via structural reorganization and confer thermo-reversible gel formation, while LR-CDs can increase aqueous solubility of guest-molecules for controlled delivery and adjust rheological behavior of starches. Moreover, 4αGT can generate bioactive glycoconjugates and novel oligosaccharides by transglycosylation. Future development of 4αGT-catalyzed reactions includes optimization by rational enzyme engineering and high-throughput screening technologies. This review portrays the immense potential of 4αGTs in sustainable biomanufacturing.

4-α-葡聚糖转移酶（4α gts），又称淀粉酶或歧化酶，在微生物、植物和动物的淀粉和糖原代谢中催化α-1,4-葡聚糖和麦芽糖低聚糖的转移。综述了它们的分类、反应、构效关系、工程及应用。4α gt属于糖苷水解酶家族GH13、GH57和GH77，可催化歧化、环化、偶联和水解四种反应，其中前两种反应在生物技术应用中尤为重要。对活性位点结构和底物结合的深入了解有助于合理设计产品特异性、作用模式和提高产品产量。这四种反应的测定包括用碘染色法监测直链淀粉的消耗、麦芽糖歧化过程中葡萄糖的释放、链长变化的色谱分析以及水解释放还原糖。淀粉转糖基化的主要反应包括支链延长的支链淀粉的形成和环化成大环环糊精（LR-CDs），也被称为环直链淀粉（CAs）。产物产率、链长分布和LR-CDs的大小取决于酶、底物和反应条件。4αGT产品在食品、生物材料和制药领域都很有用。因此，链长修饰可以通过结构重组引起淀粉对消化的抗性，并赋予热可逆凝胶形成，而LR-CDs可以增加客体分子的水溶性，以控制递送并调节淀粉的流变行为。此外，4αGT可以通过转糖基化生成具有生物活性的糖缀合物和新型低聚糖。4α gt催化反应的未来发展包括合理的酶工程优化和高通量筛选技术。这篇综述描绘了4α gt在可持续生物制造中的巨大潜力。

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引用次数: 0

Environments contaminated by pesticides are hotspots for the selection of bacterial chassis for biotechnological applications 农药污染环境是生物技术应用中细菌底盘选择的热点。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-03 DOI: 10.1016/j.biotechadv.2025.108723

Caroline Rosa Silva , Marcos Pileggi

Water storage tanks contaminated with pesticides serve as a model for an artificial ecosystem in which non-target species, particularly microorganisms, must develop various response mechanisms to survive in such environments. These mechanisms can be classified into non-specific responses, which are associated with various stressors, as well as specific responses to herbicides. Due to the stressful conditions present in these environments, they are regarded as hotspots for the selection of bacterial chassis or consortia of strains that possess combinations of genes encoding diverse phenotypes adapted for survival against a range of toxic substances. This literature review aims to extend the concept of hotspots to other aquatic and terrestrial environments contaminated with pesticides, while also discussing hypotheses regarding the potential exploitation of adapted phenotypes in biotechnological applications. These applications include bioprospecting for microorganisms that produce antimicrobial or antitumor agents, developing live biotherapeutic products for various diseases, and implementing bioremediation strategies. While well established, advances in omics technologies offer new opportunities to enhance the efficiency and safety of these strategies by manipulating gene regulatory systems. However, substantial investment is needed for genetic and metabolic manipulation. Thus, identifying selective hotspots is a beneficial strategy for obtaining viable chassis, as many organisms have already been selected in their ecosystems, along with detailing regulatory systems through omics approaches.

被农药污染的水箱可以作为人工生态系统的模型，在这种生态系统中，非目标物种，特别是微生物，必须发展出各种反应机制才能在这种环境中生存。这些机制可分为与各种应激源相关的非特异性反应和对除草剂的特异性反应。由于这些环境中存在的压力条件，它们被认为是选择细菌底盘或菌株联合体的热点，这些菌株具有编码不同表型的基因组合，适合于对抗一系列有毒物质的生存。本文献综述旨在将热点的概念扩展到其他受农药污染的水生和陆地环境，同时也讨论了关于适应表型在生物技术应用中潜在开发的假设。这些应用包括对生产抗微生物或抗肿瘤药物的微生物进行生物勘探，开发各种疾病的活生物治疗产品，以及实施生物修复策略。虽然已经建立，组学技术的进步为通过操纵基因调控系统来提高这些策略的效率和安全性提供了新的机会。然而，基因和代谢操作需要大量的投资。因此，确定选择性热点是获得可行底盘的有益策略，因为许多生物体已经在其生态系统中被选中，同时通过组学方法详细管理系统。

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引用次数: 0

Accelerated adaptive laboratory evolution: A tool for evolutionary biotechnology 加速适应实验室进化：进化生物技术的工具。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-22 DOI: 10.1016/j.biotechadv.2025.108741

Luna Declerck , Florent Bouchon , Wouter Demeester , Chiara Guidi , Marjan De Mey

Adaptive laboratory evolution (ALE) is a powerful strategy for enhancing microbial traits by harnessing the principles of natural selection in controlled environments. It has enabled significant advances in microbial growth, stress tolerance, and product yield across a variety of organisms, while also providing insight into evolutionary mechanisms. However, the traditional ALE workflow is time- and resource-intensive, relying on prolonged cultivation to allow beneficial mutations to emerge and be maintained in the population. To improve this, a range of evolutionary engineering tools have been developed to accelerate ALE by increasing mutation rates and genetic diversity in evolving strains. In this review, we explore the core parameters that shape ALE, such as selection pressure, transfer method, and passage size, and provide a comprehensive overview of both established and emerging acceleration methods. These techniques are categorized based on portability (applicability across different microorganisms), genomic targetability (specificity of mutagenesis), and reliability (minimal off-target mutations and mutational reproducibility), with the resulting framework for selecting the most suitable approach summarized in Table 3 at the end of the review. We highlight the growing potential of accelerated ALE and outline future directions, including the integration of genome-wide and targeted mutagenesis, computational modeling, laboratory automation, and broader application beyond model organisms. This review aims to streamline the use of accelerated ALE, unlocking its true potential for advancing microbial strain engineering.

适应性实验室进化（ALE）是一种在受控环境中利用自然选择原理来增强微生物特性的有力策略。它使微生物生长、抗逆性和各种生物的产品产量取得了重大进展，同时也为进化机制提供了见解。然而，传统的ALE工作流程是时间和资源密集型的，依赖于长时间的培养来允许有益的突变在种群中出现和维持。为了改善这一点，已经开发了一系列进化工程工具，通过增加进化菌株的突变率和遗传多样性来加速ALE。在这篇综述中，我们探讨了形成ALE的核心参数，如选择压力、传递方法和通道尺寸，并对现有的和新兴的加速方法进行了全面的概述。这些技术根据可移植性（在不同微生物中的适用性）、基因组靶向性（诱变的特异性）和可靠性（最小的脱靶突变和突变的可重复性）进行分类，最终选择最合适的方法的框架总结在本文最后的表3中。我们强调了加速ALE的增长潜力，并概述了未来的方向，包括全基因组和靶向诱变的整合，计算建模，实验室自动化以及模式生物以外的更广泛应用。本综述旨在简化加速ALE的使用，释放其推进微生物菌株工程的真正潜力。

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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

Biotechnology advances

Pub Date : 2026-01-01 Epub 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

Gene expression and protein abundance: Just how associated are these molecular traits? 基因表达和蛋白质丰度：这些分子特征究竟有多大的关联？

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-09-30 DOI: 10.1016/j.biotechadv.2025.108720

Anahita Samih , Maurício Alexander de Moura Ferreira , Zoran Nikoloski

The ability to accurately predict the abundance of proteins from the expression of the corresponding genes has enormous potential for the advancement of biotechnological applications using metabolic engineering and synthetic biology approaches. Addressing this problem has been challenging because of the lag in methodological advances in quantifying protein abundances. Here, we reviewed and classified studies that investigated the relationship between gene expression and protein abundance in different experimental settings and cellular contexts. We focused on comparing and contrasting the findings based on different correlation-based measures, widely used with nominal or transformed transcriptomics and proteomics data. We also included studies that investigated and attempted to explain the observed correlations between gene expression and protein abundance by incorporating data on additional factors, such as translation rate, protein degradation, and post-transcriptional modifications, using various statistical and mechanistic modelling frameworks. Finally, we provided an overview of how the latest advances using data from single-cell analyses have contributed to addressing this pressing question. Our review offers a perspective about how the findings about the relationship between gene expression and protein abundance can propel biotechnological advances, particularly focusing on opportunities resulting from the availability of protein-constrained metabolic models and the complementary machine and deep learning models.

从相应基因的表达中准确预测蛋白质丰度的能力对于利用代谢工程和合成生物学方法推进生物技术应用具有巨大的潜力。由于量化蛋白质丰度的方法进展滞后，解决这个问题一直具有挑战性。在这里，我们回顾并分类了在不同实验环境和细胞环境下研究基因表达和蛋白质丰度之间关系的研究。我们的重点是比较和对比基于不同相关性的测量结果，广泛用于名义或转化转录组学和蛋白质组学数据。我们还纳入了一些研究，这些研究试图通过结合其他因素（如翻译率、蛋白质降解和转录后修饰）的数据来解释观察到的基因表达与蛋白质丰度之间的相关性，这些研究使用了各种统计和机制建模框架。最后，我们概述了利用单细胞分析数据的最新进展如何有助于解决这一紧迫问题。我们的综述提供了一个关于基因表达和蛋白质丰度之间关系的发现如何推动生物技术进步的视角，特别是关注蛋白质受限代谢模型的可用性以及互补的机器和深度学习模型所带来的机会。

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引用次数: 0

From IscB to Cas9: Engineering and advances in the next generation of miniature gene editing tools 从IscB到Cas9：下一代微型基因编辑工具的工程和进展。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-20 DOI: 10.1016/j.biotechadv.2025.108743

Changli Zhou , Sisi Zhu , Chengjian Luo , Wenju Wang , Huiqin Fan , Yuan Gao , Xinde Xu , QiuYan Wang , Yu You , Tian Xie

The CRISPR-Cas system, distinguished by its inherent modularity and broad programmability, has catalyzed a paradigm shift in genome engineering due to its unprecedented accuracy, specificity, and on-target efficiency, now serving as the cornerstone of modern genome manipulation. The efficient delivery of gene editing tools remains a major technical hurdle to clinical application, primarily due to the lack of compact editors. The recent identification of the transposon-associated nuclease IscB as an evolutionary ancestor of Cas9 has provided important insights into the molecular evolution of the CRISPR–Cas9 system. Notably, IscB is a highly compact nuclease, approximately one-third the size of Cas9, capable of precise nucleic acid cleavage in eukaryotic cells under the guidance of ωRNA. These features make it a promising candidate for the development of next-generation miniaturized genome editors. However, natural IscB exhibits limited editing performance in eukaryotic systems.

This review first outlines the biochemical function of the transposon IscB and briefly traces the evolutionary origin of the Cas9 system. It then describes and compares the structural characteristics and cleavage mechanisms of OgeuIscB and Cas9. Subsequent sections summarize various engineering strategies for current IscB systems, including the development of base editors and recent advances in their application. Finally, the limitations of existing systems are discussed, and potential directions for future optimization are proposed, aiming to provide new insights and facilitate the advancement of IscB-based miniaturized editors.

CRISPR-Cas系统以其固有的模块化和广泛的可编程性而闻名，由于其前所未有的准确性、特异性和靶向效率，催化了基因组工程的范式转变，现在成为现代基因组操作的基石。基因编辑工具的有效传递仍然是临床应用的主要技术障碍，主要是由于缺乏紧凑型编辑器。最近发现转座子相关核酸酶IscB是Cas9的进化祖先，这为CRISPR-Cas9系统的分子进化提供了重要的见解。值得注意的是，IscB是一种高度紧凑的核酸酶，大小约为Cas9的三分之一，能够在ωRNA的指导下在真核细胞中精确切割核酸。这些特点使其成为开发下一代小型化基因组编辑器的一个有希望的候选者。然而，天然IscB在真核系统中表现出有限的编辑性能。本文首先概述了转座子IscB的生化功能，并简要追溯了Cas9系统的进化起源。然后描述并比较了OgeuIscB和Cas9的结构特征和裂解机制。随后的部分总结了当前IscB系统的各种工程策略，包括碱基编辑器的发展及其应用的最新进展。最后，讨论了现有系统的局限性，并提出了未来优化的潜在方向，旨在为基于iscb的小型化编辑器的发展提供新的见解。

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引用次数: 0

Microbial quorum sensing: Mechanisms, applications, and challenges 微生物群体感应：机制、应用和挑战。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-06 DOI: 10.1016/j.biotechadv.2025.108733

Qi Ruan , Shuting Geng , Jianqiu Yu , Leilei Lu , Yanhua Liu , Jianqiu Chen , Qianjiahua Liao , Ruixin Guo

Quorum sensing (QS) is a sophisticated microbial communication system that orchestrates gene expression in response to population density, governing collective behaviors crucial for microbial survival and function. This comprehensive review elucidates the intricate synthesis pathways and mechanisms of QS signaling molecules across diverse microbial species. We critically analyze the multifaceted applications of QS in healthcare, agriculture, and environmental biotechnology, highlighting its potential to revolutionize these fields. The review also explores quorum quenching (QQ) strategies as a novel approach to microbial control and examines the unique adaptations of QS systems in extreme environments. By synthesizing recent advancements and identifying knowledge gaps, we outline pressing challenges and propose promising future research directions. This work aims to provide a roadmap for leveraging QS in developing innovative biotechnological solutions to address global challenges in health, food security, and environmental sustainability.

群体感应（Quorum sensing， QS）是一种复杂的微生物通讯系统，它根据种群密度协调基因表达，控制对微生物生存和功能至关重要的集体行为。本文综述了QS信号分子在不同微生物物种中复杂的合成途径和机制。我们批判性地分析了QS在医疗保健、农业和环境生物技术方面的多方面应用，强调了它在这些领域的革命性潜力。这篇综述还探讨了群体猝灭（QQ）策略作为一种新的微生物控制方法，并研究了QS系统在极端环境中的独特适应性。通过综合最近的进展和识别知识差距，我们概述了紧迫的挑战，并提出了有希望的未来研究方向。这项工作旨在为利用QS开发创新生物技术解决方案提供路线图，以应对健康、粮食安全和环境可持续性方面的全球挑战。

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引用次数: 0

Adaptability and resiliency of Lepidoptera and their cells in culture - linking evolutionary biology to biotechnological advantage 鳞翅目及其细胞在培养中的适应性和弹性——将进化生物学与生物技术优势联系起来。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-01 DOI: 10.1016/j.biotechadv.2025.108721

Sophia Letcher , Barry Trimmer , David L. Kaplan

Lepidopteran cells are an important tool for producing recombinant proteins, vaccines, and other biomolecules, and there is growing interest in using lepidopteran cells for other industries such as cultivated meat or as bioactuators. Lepidopteran cells are favored over mammalian cells for these applications because they grow in relatively simple systems in low-cost culture media and are adaptable to a wide range of culture conditions. Although these advantages of lepidopteran cells are well known, the mechanistic basis for these advantages are not well understood. Here, we consider the evolutionary and physiological pressures guiding cell-level adaptations in Lepidoptera and how these adaptations lead to favorable cell culture behavior. Specifically, we link lepidopteran cell resiliency (i.e., ability to withstand environmental stressors) with a robust antioxidant system, altered chromosome structure, polyploidy, and pre-conditioning of cell stress pathways. We also link lepidopteran cell adaptability (i.e., ability to grow in a range of media formulations) to metabolic flexibility, variable resource allocation options and efficient energy budgeting. We then consider the evolutionary pressures that led to selection for these favorable cell culture traits, including exposure to high oxidative stress, environmental clastogens, small size, metamorphosis, and limited food access and diversity. Finally, we highlight key future experiments to facilitate an improved understanding of lepidopteran resiliency and adaptability for biomanufacturing goals with insect cells, as well as ideas for utilizing this knowledge to improve vertebrate cell culture.

鳞翅目细胞是生产重组蛋白、疫苗和其他生物分子的重要工具，人们对将鳞翅目细胞用于其他行业（如养殖肉类或作为生物致动器）的兴趣日益浓厚。鳞翅目细胞在这些应用中比哺乳动物细胞更受青睐，因为它们在相对简单的系统中生长，在低成本的培养基中生长，并且适应广泛的培养条件。虽然鳞翅目细胞的这些优点是众所周知的，但这些优点的机制基础还不是很清楚。在这里，我们考虑进化和生理压力指导鳞翅目细胞水平的适应，以及这些适应如何导致有利的细胞培养行为。具体来说，我们将鳞翅目细胞的弹性（即承受环境压力的能力）与强大的抗氧化系统、改变的染色体结构、多倍体和细胞应激途径的预处理联系起来。我们还将鳞翅目细胞的适应性（即在各种培养基配方中生长的能力）与代谢灵活性、可变资源分配选择和有效的能量预算联系起来。然后，我们考虑了导致这些有利的细胞培养特性选择的进化压力，包括暴露于高氧化应激、环境致裂原、小尺寸、变态、有限的食物获取和多样性。最后，我们强调了未来的关键实验，以促进对鳞翅目昆虫细胞生物制造目标的弹性和适应性的更好理解，以及利用这些知识改进脊椎动物细胞培养的想法。

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引用次数: 0

Material-binding peptides: sources, mechanisms, directed evolution and applications 物质结合肽：来源、机制、定向进化和应用。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-16 DOI: 10.1016/j.biotechadv.2025.108742

Huan Chen , Ya-Ting Gao , Xu-Zhe Ge , Xin Wang , Feng Cheng , Ya-Ping Xue , Yu-Guo Zheng

Material-binding peptides (MBPs) can specifically bind to materials under mild conditions, such as room temperature and aqueous environments, thereby offering promising applications in both biotechnology and materials science. Recent advances in screening techniques, including phage display, bacterial display, and proteomics-based methods, combined with innovations in protein engineering and machine learning, have significantly accelerated the discovery and optimization of MBPs. These peptides have been successfully applied in areas such as catalyst immobilization (biocatalysis), biodegradation, and biomimetic mineralization. This review provides a comprehensive synthesis of the state-of-the-art in MBP research. It begins by discussing the sources of MBPs and the engineering strategies used to enhance their performance, then delves into the molecular mechanisms underlying their material interactions, and finally examines their emerging industrial applications. The review aims to guide researchers through current screening methodologies, provide mechanistic insights, and explore practical applications, offering a roadmap for future advancements in the field.

材料结合肽（MBPs）可以在室温和水环境等温和条件下特异性结合材料，因此在生物技术和材料科学中都有很好的应用前景。筛选技术的最新进展，包括噬菌体展示、细菌展示和基于蛋白质组学的方法，结合蛋白质工程和机器学习的创新，极大地加速了MBPs的发现和优化。这些多肽已成功应用于催化剂固定化（生物催化）、生物降解和仿生矿化等领域。本文综述了MBP研究的最新进展。首先讨论MBPs的来源和用于提高其性能的工程策略，然后深入研究其材料相互作用的分子机制，最后研究其新兴的工业应用。该综述旨在指导研究人员了解当前的筛选方法，提供机制见解，并探索实际应用，为该领域的未来发展提供路线图。

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引用次数: 0

Smart culture medium optimization for recombinant protein production: Experimental, modeling, and AI/ML-driven strategies 重组蛋白生产的智能培养基优化：实验、建模和AI/ ml驱动策略。

IF 12.5 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2026-01-01 Epub Date: 2025-10-15 DOI: 10.1016/j.biotechadv.2025.108738

Galib Khan , Carrie Sanford , Cong T. Trinh

Recombinant protein production (RPP) is central to biotechnology, where recombinant proteins are used as either end products or catalysts in the synthesis of chemicals, fuels, and materials. Among the major cost drivers, culture medium plays a pivotal role in determining protein yield and quality. This review presents a comprehensive perspective on the critical stages of “smart” culture medium optimization: planning, screening, modeling, optimization, and validation. In the planning stage, we examine the nutritional and energetic roles of medium components, including carbon, nitrogen, amino acids, salts, and trace metals, and their impacts on culture parameters such as pH, oxidative state, and osmolality. We highlight the variability in trace metal content due to water sources, culture vessels, and raw materials, which can substantially influence RPP. The screening stage covers Design of Experiments (DoE) approaches, assessing their theoretical basis, implementation, and limitations. For modeling, we describe methods that integrate experimental data to develop predictive models for smart medium formulation. Model-based optimization strategies can then be employed to select optimal media compositions for a given application. The validation stage aims to evaluate model predictions and provide feedback for model training and refinement. Finally, we survey mechanistic and artificial intelligence/machine learning (AI/ML)-driven models as integrated, transformational tools for predictive modeling of bioprocess conditions, nutrient availability, cellular metabolism, and protein quality, with the goal of optimizing culture media to enhance protein yields while reducing costs and environmental impact. We conclude by addressing the challenges of translating laboratory-scale medium optimization to industrial-scale settings and exploring future AI/ML-driven approaches that may overcome current bottlenecks and accelerate medium design for RPP. Overall, this review provides a unified framework for advancing smart medium design in RPP.

重组蛋白生产（RPP）是生物技术的核心，重组蛋白被用作合成化学品、燃料和材料的最终产品或催化剂。在主要的成本驱动因素中，培养基在决定蛋白质产量和质量方面起着关键作用。本文综述了“智能”培养基优化的关键阶段：规划、筛选、建模、优化和验证。在计划阶段，我们研究了培养基成分的营养和能量作用，包括碳、氮、氨基酸、盐和微量金属，以及它们对pH、氧化状态和渗透压等培养参数的影响。我们强调了由于水源、培养容器和原材料而引起的微量金属含量的变化，这些变化会极大地影响RPP。筛选阶段包括实验设计（DoE）方法，评估其理论基础，实施和局限性。对于建模，我们描述了整合实验数据以开发智能介质配方预测模型的方法。然后可以使用基于模型的优化策略为给定的应用程序选择最佳的媒体组合。验证阶段的目的是评估模型预测，并为模型训练和改进提供反馈。最后，我们调查了机械和人工智能/机器学习（AI/ML）驱动的模型，作为生物过程条件、营养可用性、细胞代谢和蛋白质质量预测建模的集成转换工具，目的是优化培养基，提高蛋白质产量，同时降低成本和环境影响。最后，我们解决了将实验室规模的介质优化转化为工业规模设置的挑战，并探索了未来人工智能/机器学习驱动的方法，这些方法可能克服当前的瓶颈，并加速RPP的介质设计。总之，这篇综述为推进RPP中的智能介质设计提供了一个统一的框架。

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