Biotechnology advances最新文献_第6页

From discovery to application: Enabling technology-based optimizing carbonyl reductases biocatalysis for active pharmaceutical ingredient synthesis 从发现到应用：使基于技术的优化羰基还原酶生物催化活性药物成分合成。

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-12-06 DOI: 10.1016/j.biotechadv.2024.108496

Jie Gu , Wanmeng Mu , Yan Xu , Yao Nie

The catalytic conversion of chiral alcohols and corresponding carbonyl compounds by carbonyl reductases (alcohol dehydrogenases), which are NAD(P) or NAD(P)H-dependent oxidoreductases, has attracted considerable attention. However, existing carbonyl reductases are insufficient to meet the demands of diverse industrial applications; hence, new enzymes with functions that can expand the toolbox of biocatalysts are urgently required. Developing precisely controlled chiral biocatalysts is of great significance for the efficient development of a broad spectrum of active pharmaceutical ingredients via biosynthesis. In this review, we summarized methods for discovering novel natural carbonyl reductases from various perspectives. Furthermore, advances in protein engineering, utilizing known sequence and structural information as well as catalytic dynamics mechanisms to improve potential functions, are also addressed. The exponential growth in data-driven tools over the past decade has made it possible to de novo design carbonyl reductases. Additionally, various applications of these high-performance carbonyl reductases and different strategies for coenzyme regeneration involving photocatalysis during the reaction process were reviewed. These advancements will bring new opportunities and challenges to the fields of green chemistry and biosynthesis in the future.

依赖于NAD(P)或NAD(P) h的羰基还原酶（醇脱氢酶）催化手性醇及其相应羰基化合物的转化引起了广泛的关注。然而，现有的羰基还原酶不足以满足各种工业应用的需求；因此，迫切需要具有扩展生物催化剂工具箱功能的新型酶。开发精确控制的手性生物催化剂对于通过生物合成高效开发广谱活性药物成分具有重要意义。本文综述了从不同角度发现新型天然羰基还原酶的方法。此外，还介绍了蛋白质工程的进展，利用已知的序列和结构信息以及催化动力学机制来改善潜在的功能。在过去的十年中，数据驱动工具的指数级增长使得重新设计羰基还原酶成为可能。此外，综述了这些高性能羰基还原酶的各种应用以及在反应过程中涉及光催化的辅酶再生的不同策略。这些进展将给未来的绿色化学和生物合成领域带来新的机遇和挑战。

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引用次数: 0

Direct cloning strategies for large genomic fragments: A review 大片段基因组直接克隆策略综述

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-12-06 DOI: 10.1016/j.biotechadv.2024.108494

Ya-Nan Chen , You-Zhi Cui , Xiang-Rong Chen , Jun-Yi Wang , Bing-Zhi Li , Ying-Jin Yuan

Mining large-scale functional regions of the genome helps to understand the essence of cellular life. The rapid accumulation of genomic information provides a wealth of material for genomic functional, evolutionary, and structural research. DNA cloning technology is an important tool for understanding, analyzing, and manipulating the genetic code of organisms. As synthetic biologists engineer greater and broader genetic pathways and expand their research into new organisms, efficient tools capable of manipulating large-scale DNA will offer momentum to the ability to design, modify, and construct engineering life. In this review, we discuss the recent advances in the field of direct cloning of large genomic fragments, particularly of 50–150 kb genomic fragments. We specifically introduce the technological advances in the targeted release and capture steps of these cloning strategies. Additionally, the applications of large fragment cloning in functional genomics and natural product mining are also summarized. Finally, we further discuss the challenges and prospects for these technologies in the future.

挖掘基因组的大规模功能区域有助于理解细胞生命的本质。基因组信息的快速积累为基因组功能、进化和结构研究提供了丰富的材料。DNA克隆技术是理解、分析和操纵生物遗传密码的重要工具。随着合成生物学家设计更大和更广泛的遗传途径，并将他们的研究扩展到新的生物体，能够操纵大规模DNA的有效工具将为设计、修改和构建工程生命的能力提供动力。本文综述了近年来大片段基因组直接克隆的研究进展，特别是50-150 kb基因组片段的直接克隆。我们特别介绍了这些克隆策略的目标释放和捕获步骤的技术进步。综述了大片段克隆技术在功能基因组学和天然产物挖掘中的应用。最后，我们进一步讨论了这些技术在未来面临的挑战和前景。

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引用次数: 0

Is it possible to shape the microalgal biomass composition with operational parameters for target compound accumulation? 是否有可能用目标化合物积累的操作参数来塑造微藻生物量组成？

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-12-05 DOI: 10.1016/j.biotechadv.2024.108493

Ana F. Esteves , Ana L. Gonçalves , Vítor J.P. Vilar , José C.M. Pires

Microalgae, as photosynthetic microorganisms, offer a sustainable source of proteins, lipids, carbohydrates, pigments, vitamins, and antioxidants. Leveraging their advantages, such as fast growth, CO₂ fixation, cultivation without arable land, and wastewater utilisation, microalgae can produce a diverse range of compounds. The extracted products find applications in bioenergy, animal feed, pharmaceuticals, nutraceuticals, cosmetics, and food industries. The selection of microalgal species is crucial, and their biochemical composition varies during growth phases influenced by environmental factors like light, salinity, temperature, and nutrients. Manipulating growth conditions shapes biomass composition, optimising the production of target compounds.

This review synthesises research from 2019 onwards, focusing on stress induction and two-stage cultivation in microalgal strategies. This review takes a broader approach, addressing the effects of various operating conditions on a range of biochemical compounds. It explores the impact of operational parameters (light, nutrient availability, salinity, temperature) on biomass composition, elucidating microalgal mechanisms. Challenges include species-specific responses, maintaining stable conditions, and scale-up complexities. A two-stage approach balances biomass productivity and compound yield. Overcoming challenges involves improving upstream and downstream processes, developing sophisticated monitoring systems, and conducting further modelling work. Future efforts should concentrate on strain engineering and refined monitoring, facilitating real-time adjustments for optimal compound accumulation. Moreover, conducting large-scale experiments is essential to evaluate the feasibility and sustainability of the process through techno-economic analysis and life cycle assessments.

微藻作为一种光合微生物，提供了蛋白质、脂质、碳水化合物、色素、维生素和抗氧化剂的可持续来源。利用其快速生长、二氧化碳固定、无需耕地种植和废水利用等优势，微藻可以生产各种化合物。提取的产品在生物能源、动物饲料、药品、保健品、化妆品和食品工业中都有应用。微藻的种类选择是至关重要的，其生化组成在生长阶段受到光、盐度、温度和营养等环境因素的影响。操纵生长条件塑造生物质组成，优化目标化合物的生产。本文综述了自2019年以来的研究，重点关注微藻策略中的应激诱导和两阶段培养。这篇综述采取了更广泛的方法，解决了各种操作条件对一系列生化化合物的影响。它探讨了操作参数（光，养分有效性，盐度，温度）对生物量组成的影响，阐明了微藻的机制。挑战包括物种特有的反应、维持稳定的条件和扩大的复杂性。两阶段方法平衡生物质生产力和复合产量。克服挑战需要改进上游和下游流程，开发复杂的监测系统，并开展进一步的建模工作。未来的工作应集中在应变工程和精细监测上，以便实时调整最佳的化合物积累。此外，通过技术经济分析和生命周期评估，进行大规模实验对评价该过程的可行性和可持续性至关重要。

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引用次数: 0

Engineering microbial cell factories by multiplexed spatiotemporal control of cellular metabolism: Advances, challenges, and future perspectives 通过多重时空控制细胞代谢的工程微生物细胞工厂：进展、挑战和未来展望。

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-12-05 DOI: 10.1016/j.biotechadv.2024.108497

Wenwen Yu , Ke Jin , Xianhao Xu , Yanfeng Liu , Jianghua Li , Guocheng Du , Jian Chen , Xueqin Lv , Long Liu

Generally, the metabolism in microbial organism is an intricate, spatiotemporal process that emerges from gene regulatory networks, which affects the efficiency of product biosynthesis. With the coming age of synthetic biology, spatiotemporal control systems have been explored as versatile strategies to promote product biosynthesis at both spatial and temporal levels. Meanwhile, the designer synthetic compartments provide new and promising approaches to engineerable spatiotemporal control systems to construct high-performance microbial cell factories. In this article, we comprehensively summarize recent developments in spatiotemporal control systems for tailoring advanced cell factories, and illustrate how to apply spatiotemporal control systems in different microbial species with desired applications. Future challenges of spatiotemporal control systems and perspectives are also discussed.

一般来说，微生物的代谢是一个复杂的时空过程，是由基因调控网络产生的，它影响着产物的生物合成效率。随着合成生物学时代的到来，时空控制系统已被探索为在空间和时间水平上促进产品生物合成的通用策略。同时，设计合成隔间为构建高性能微生物细胞工厂的可工程时空控制系统提供了新的和有前途的方法。在本文中，我们全面总结了用于定制先进细胞工厂的时空控制系统的最新进展，并说明了如何将时空控制系统应用于不同的微生物物种。本文还讨论了时空控制系统的未来挑战和前景。

引用次数: 0

Interpretable and explainable predictive machine learning models for data-driven protein engineering 用于数据驱动蛋白质工程的可解释和可解释的预测机器学习模型。

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-12-05 DOI: 10.1016/j.biotechadv.2024.108495

David Medina-Ortiz , Ashkan Khalifeh , Hoda Anvari-Kazemabad , Mehdi D. Davari

Protein engineering through directed evolution and (semi)rational design has become a powerful approach for optimizing and enhancing proteins with desired properties. The integration of artificial intelligence methods has further accelerated protein engineering process by enabling the development of predictive models based on data-driven strategies. However, the lack of interpretability and transparency in these models limits their trustworthiness and applicability in real-world scenarios. Explainable Artificial Intelligence addresses these challenges by providing insights into the decision-making processes of machine learning models, enhancing their reliability and interpretability. Explainable strategies has been successfully applied in various biotechnology fields, including drug discovery, genomics, and medicine, yet its application in protein engineering remains underexplored. The incorporation of explainable strategies in protein engineering holds significant potential, as it can guide protein design by revealing how predictive models function, benefiting approaches such as machine learning-assisted directed evolution. This perspective work explores the principles and methodologies of explainable artificial intelligence, highlighting its relevance in biotechnology and its potential to enhance protein design. Additionally, three theoretical pipelines integrating predictive models with explainable strategies are proposed, focusing on their advantages, disadvantages, and technical requirements. Finally, the remaining challenges of explainable artificial intelligence in protein engineering and future directions for its development as a support tool for traditional protein engineering methodologies are discussed.

通过定向进化和（半）理性设计的蛋白质工程已成为优化和增强具有所需特性的蛋白质的有力方法。人工智能方法的集成通过基于数据驱动策略的预测模型的开发，进一步加速了蛋白质工程的进程。然而，这些模型缺乏可解释性和透明度，限制了它们在现实场景中的可信度和适用性。可解释的人工智能通过洞察机器学习模型的决策过程，提高其可靠性和可解释性来解决这些挑战。可解释策略已成功地应用于各种生物技术领域，包括药物发现、基因组学和医学，但其在蛋白质工程中的应用仍有待探索。蛋白质工程中可解释策略的结合具有巨大的潜力，因为它可以通过揭示预测模型的功能来指导蛋白质设计，有利于机器学习辅助定向进化等方法。这项前瞻性工作探讨了可解释人工智能的原理和方法，强调了其在生物技术中的相关性及其增强蛋白质设计的潜力。此外，提出了三种将预测模型与可解释策略相结合的理论管道，重点分析了它们的优缺点和技术要求。最后，讨论了可解释人工智能在蛋白质工程中的剩余挑战，以及其作为传统蛋白质工程方法的支持工具的未来发展方向。

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引用次数: 0

Current innovations in mRNA vaccines for targeting multidrug-resistant ESKAPE pathogens 针对多药耐药ESKAPE病原体的mRNA疫苗的最新创新。

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-12-03 DOI: 10.1016/j.biotechadv.2024.108492

Saber Imani , Shuojie Lv , Hongbo Qian , Yulan Cui , XiaoYan Li , Ali Babaeizad , Qingjing Wang

The prevalence of multidrug-resistant (MDR) ESKAPE pathogens, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa, represents a critical global public health challenge. In response, mRNA vaccines offer an adaptable and scalable platform for immunotherapy against ESKAPE pathogens by encoding specific antigens that stimulate B-cell-driven antibody production and CD8⁺ T-cell-mediated cytotoxicity, effectively neutralizing these pathogens and combating resistance. This review examines recent advancements and ongoing challenges in the development of mRNA vaccines targeting MDR ESKAPE pathogens. We explore antigen selection, the nuances of mRNA vaccine technology, and the complex interactions between bacterial infections and antibiotic resistance. By assessing the potential efficacy of mRNA vaccines and addressing key barriers to their paraclinical implementation, this review highlights the promising function of mRNA-based immunization in combating MDR ESKAPE pathogens.

包括屎肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌和铜绿假单胞菌在内的多药耐药ESKAPE病原体的流行是一项重大的全球公共卫生挑战。因此，mRNA疫苗通过编码特异性抗原，刺激b细胞驱动的抗体产生和CD8+ t细胞介导的细胞毒性，有效中和这些病原体并对抗耐药性，为ESKAPE病原体的免疫治疗提供了一个适应性强、可扩展的平台。本文综述了针对MDR ESKAPE病原体的mRNA疫苗的最新进展和面临的挑战。我们探索抗原选择，mRNA疫苗技术的细微差别，以及细菌感染和抗生素耐药性之间的复杂相互作用。通过评估mRNA疫苗的潜在功效和解决其临床应用的关键障碍，本综述强调了mRNA免疫在对抗耐多药ESKAPE病原体方面的有希望的功能。

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引用次数: 0

Selection of aptamers targeting small molecules by capillary electrophoresis: Advances, challenges, and prospects 通过毛细管电泳选择以小分子为靶标的适配体：进展、挑战与前景。

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-11-26 DOI: 10.1016/j.biotechadv.2024.108491

Yangyang Hu , Guangyu Jiang , Yalun Wen , Yuchen Shao , Ge Yang , Feng Qu

Aptamers, as novel recognition molecules, hold immense potential across various domains such as biosensing, nucleic acid drugs, medical diagnostics, as well as environmental and food analysis. The majority of aptamer selection processes targeting small molecules and protein commonly employ magnetic bead-based methodologies, wherein the target is initially immobilized on magnetic beads, followed by magnetic separation. The Evolutionary Systematic Evolution of Ligands by Exponential Enrichment technique based on capillary electrophoresis (CE-SELEX) is acknowledged as one of the most efficient screening methods. Our research group has achieved breakthroughs in employing CE-SELEX for the selection of aptamers targeting small molecules. This paper outlines specific methodologies utilized from 2005 to 2023 for CE-SELEX screening for small-molecule targets. It summarizes the methods for the separation of small molecules and oligonucleotide complexes, as well as the identification of candidate aptamers. Drawing upon our research group's extensive experience in CE-SELEX for selecting aptamers targeting multi-scale targets, we offer strategic guidance specifically tailored to the screening of aptamers for small-molecule targets using CE-SELEX. This includes systematic insights into each technical aspect of the screening process: analysis of the structure of small-molecule targets and characteristics of ssDNA libraries, patterns of CE separation and collection of complexes, screening strategies, and CE-based methods for the affinity and specificity characterization of aptamers. This comprehensive review aims to contribute to the widespread adoption of CE-SELEX technology, enhancing the efficiency and success rate of selecting aptamers for small-molecule targets.

适配体作为新型识别分子，在生物传感、核酸药物、医疗诊断以及环境和食品分析等各个领域都具有巨大的潜力。大多数以小分子和蛋白质为目标的适配体选择过程通常采用基于磁珠的方法，即首先将目标固定在磁珠上，然后进行磁分离。基于毛细管电泳的配体指数富集系统进化技术（CE-SELEX）被公认为最有效的筛选方法之一。我们的研究小组在利用 CE-SELEX 筛选小分子适配体方面取得了突破性进展。本文概述了从 2005 年到 2023 年用于小分子靶标 CE-SELEX 筛选的具体方法。它总结了分离小分子和寡核苷酸复合物以及鉴定候选适配体的方法。我们的研究小组在利用 CE-SELEX 筛选针对多尺度靶标的适配体方面积累了丰富的经验，在此基础上，我们提供了专门针对利用 CE-SELEX 筛选针对小分子靶标的适配体的战略指导。其中包括对筛选过程中每个技术环节的系统见解：小分子靶标结构和 ssDNA 文库特征的分析、CE 分离和收集复合物的模式、筛选策略以及基于 CE 的适配体亲和性和特异性表征方法。本综述旨在促进 CE-SELEX 技术的广泛应用，提高为小分子靶标选择适配体的效率和成功率。

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引用次数: 0

Expanding the frontiers of genome engineering: A comprehensive review of CRISPR-associated transposons 拓展基因组工程的前沿：CRISPR相关转座子的全面回顾。

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-11-22 DOI: 10.1016/j.biotechadv.2024.108481

Cheng Chen , Ya-Wen Li , Yuan-Yuan Zheng , Xiu-Juan Li , Na Wu , Qi Guo , Tian-Qiong Shi , He Huang

Genome engineering is extensively utilized in diverse scientific disciplines, advancing human welfare and addressing various challenges. Numerous genome engineering tools have been developed to modify genomic sequences. Among these, the CRISPR-Cas system has transformed the field and remains the most commonly employed genome-editing tool. However, the CRISPR-Cas system relies on induced double-strand breaks, with editing efficiency often limited by factors such as cell type and homologous recombination, impeding further progress. CRISPR-associated transposons (CASTs) represent programmable mobile genetic elements. CASTs identified as active were developed as CAST systems, which can perform RNA-guided DNA integration and are featured by high precision, programmability, and kilobase-level payload capacity. Moreover, CAST system allows for precise genome modifications independent of host DNA repair mechanisms, addressing the constraints of conventional CRISPR-Cas systems. It expands the genome engineering toolkit and is poised to become a representative of next-generation genome editing tools. This review thoroughly examines the research progress on CASTs, highlighting the current challenges faced in genome engineering based on CASTs, and offering insights into the ongoing development of this transformative technology.

基因组工程被广泛应用于不同的科学学科，增进人类福祉，应对各种挑战。目前已开发出许多基因组工程工具来修改基因组序列。其中，CRISPR-Cas 系统改变了这一领域，至今仍是最常用的基因组编辑工具。然而，CRISPR-Cas 系统依赖于诱导双链断裂，其编辑效率往往受到细胞类型和同源重组等因素的限制，阻碍了其进一步发展。CRISPR 相关转座子（CAST）是可编程的移动遗传元件。被鉴定为具有活性的 CAST 被开发为 CAST 系统，它可以执行 RNA 引导的 DNA 整合，具有高精度、可编程和千碱基级有效载荷容量的特点。此外，CAST 系统可以不受宿主 DNA 修复机制的影响，对基因组进行精确修饰，解决了传统 CRISPR-Cas 系统的局限性。它扩展了基因组工程工具包，有望成为下一代基因组编辑工具的代表。这篇综述深入探讨了 CAST 的研究进展，强调了当前基于 CAST 的基因组工程所面临的挑战，并对这一变革性技术的持续发展提出了见解。

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引用次数: 0

A non-classical view of antibody properties: Allosteric effect between variable and constant regions 抗体特性的非经典观点：可变区和恒定区之间的异化作用

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-11-21 DOI: 10.1016/j.biotechadv.2024.108482

Xiaoting Yu , Huiling Zhang , Tao Zhou , Kangliang Pan , Sayed Haidar Abbas Raza , Xing Shen , Hongtao Lei

Historically, antibodies have been divided into two functionally independent domains, the variable (V) region for antigen binding and the constant (C) region for mediating effector functions. However, this classical view of antibody function has been severely challenged by a large and growing number of studies, which reveal long-range conformational interactions and allosteric links between the V and C regions. This review comprehensively summarizes the existing studies on antibody allostery, including allosteric conformational changes induced by covalent modifications or noncovalent ligand binding. In addition, we discuss how intramolecular allosteric signals are transmitted from the V to C regions and vice versa. This review argues that there is sufficient evidence to revisit the structure-function relationship of antibodies. These advances in antibody allostery will provide a blueprint for regulating antibody functions in a simple and highly predictable manner. More focus on antibody allostery will definitely benefit antibody engineering and vaccine design in the field of biotechnology.

一直以来，抗体被划分为两个功能独立的结构域，可变区（V）用于抗原结合，恒定区（C）用于介导效应功能。然而，大量且日益增多的研究揭示了 V 区和 C 区之间的长程构象相互作用和异构联系，这对抗体功能的经典观点提出了严峻挑战。本综述全面总结了现有的抗体异构研究，包括共价修饰或非共价配体结合诱导的异构构象变化。此外，我们还讨论了分子内异构信号如何从 V 区传递到 C 区，反之亦然。这篇综述认为，有足够的证据可以重新审视抗体的结构-功能关系。抗体异构研究的这些进展将为以简单和高度可预测的方式调节抗体功能提供蓝图。对抗体异构的更多关注必将有利于生物技术领域的抗体工程和疫苗设计。

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引用次数: 0

Advances and challenges in preparing membrane proteins for native mass spectrometry 为原生质谱法制备膜蛋白的进展与挑战

IF 12.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology advances

Pub Date : 2024-11-20 DOI: 10.1016/j.biotechadv.2024.108483

Di Cheng , Yi Guo , Jixing Lyu , Yang Liu , Wenhao Xu , Weiyi Zheng , Yuchen Wang , Pei Qiao

Native mass spectrometry (nMS) is becoming a crucial tool for analyzing membrane proteins (MPs), yet challenges remain in solubilizing and stabilizing their native conformations while resolving and characterizing the heterogeneity introduced by post-translational modifications and ligand binding. This review highlights recent advancements and persistent challenges in preparing MPs for nMS. Optimizing detergents and additives can significantly reduce sample heterogeneity and surface charge, enhancing MP signal quality and structural preservation in nMS. A strategic workflow incorporating affinity capture, stabilization agents, and size-exclusion chromatography to remove unfolded species demonstrates success in improving nMS characterization. Continued development of customized detergents and reagents tailored for specific MPs may further minimize heterogeneity and boost signals. Instrumental advances are also needed to elucidate more dynamically complex and labile MPs. Effective sample preparation workflows may provide insights into MP structures, dynamics, and interactions underpinning membrane biology. With ongoing methodological innovation, nMS shows promise to complement biophysical studies and facilitate drug discovery targeting this clinically important yet technically demanding protein class.

原生质谱（nMS）正成为分析膜蛋白（MPs）的重要工具，但在溶解和稳定其原生构象，同时解析和表征翻译后修饰和配体结合带来的异质性方面仍存在挑战。本综述重点介绍了在制备用于 nMS 的 MPs 方面的最新进展和长期挑战。优化去垢剂和添加剂可大大降低样品的异质性和表面电荷，从而提高 MP 信号质量和 nMS 中的结构保存。将亲和捕获、稳定剂和尺寸排阻色谱法结合起来以去除未折叠物种的战略工作流程在改进 nMS 表征方面取得了成功。继续开发针对特定 MPs 的定制去垢剂和试剂可进一步减少异质性并提高信号。此外，还需要在仪器方面取得进展，以阐明更为动态复杂和易变的 MPs。有效的样品制备工作流程可让人们深入了解膜生物学中的 MP 结构、动力学和相互作用。随着方法的不断创新，nMS有望补充生物物理研究，促进针对这一临床上重要但技术要求高的蛋白质类别的药物发现。

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引用次数: 0