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Coupling between the cell cycle and the circadian clock: Lessons from computational modelling and consequences for cancer chronotherapy 细胞周期与昼夜节律时钟之间的耦合:计算建模的启示及对癌症时间疗法的影响
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-02-01 DOI: 10.1016/j.coisb.2024.100507
Didier Gonze

Chronotherapy aims at optimising the time of day and dosing of drugs administration. This is a promising perspective because the toxicity and efficacy of many drugs show a dependence on the time of the day at which they are administrated. Efficient cancer chronotherapy requires a good understanding of the interplay between the cell cycle and the circadian clock. Computational models offer a way to study the dynamics resulting from the coupling between these two biological oscillators and to predict successful therapeutic protocols. We review here recent advances and highlight key challenges for further developments of predictive mathematical models.

时间疗法旨在优化每天的用药时间和剂量。这是一个很有前景的观点,因为许多药物的毒性和疗效都与一天中的用药时间有关。高效的癌症时间疗法需要充分了解细胞周期与昼夜节律时钟之间的相互作用。计算模型为研究这两种生物振荡器之间的耦合所产生的动态变化以及预测成功的治疗方案提供了一种方法。我们在此回顾了最近的研究进展,并强调了进一步开发预测性数学模型所面临的主要挑战。
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引用次数: 0
Biodegradation of polystyrene and systems biology-based approaches to the development of new biocatalysts for plastic degradation 聚苯乙烯的生物降解和基于系统生物学的塑料降解新生物催化剂开发方法
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-12 DOI: 10.1016/j.coisb.2024.100505
Ye-Bin Kim , Seongmin Kim , Chungoo Park , Soo-Jin Yeom

Plastic waste has become one of the most pressing environmental issues with rapidly increased their production that also has a severe impact on individual species and ecosystem functioning.

With recycling technologies in place, the waste plastic will become a valuable resource and hence less material will be lost to the environment. In the pursuit of a sustainable approach to the treatment of plastic waste, biological processes have emerged as an eco-friendly method with significant potential. In this review, we summarize previous research on the biodegradation of polystyrene (PS) as major plastics, including a review of the analytical methods used to investigate the plastic biodegradation, the isolation of PS-degrading microbes from various environment, and the identification of potential enzymes for PS biodegradation. Based on this, we propose a potential PS biodegradation pathway, even though the specific biochemical mechanisms associated with certain enzymes have not yet been fully identified. Finally, we discuss how PS-biodegrading enzymes can be identified using a systems biology-based screening approach that combines culture-based genomic and culture-independent metagenomic methods. This strategy can be applied to searching biodegrading enzymes for other plastics.

随着塑料产量的迅速增加,塑料废物已成为最紧迫的环境问题之一,同时也对物种个体和生态系统功能产生了严重影响。为了寻求一种可持续的方法来处理塑料废物,生物工艺已成为一种具有巨大潜力的生态友好型方法。在这篇综述中,我们总结了以往关于聚苯乙烯(PS)作为主要塑料的生物降解的研究,包括用于研究塑料生物降解的分析方法、从各种环境中分离聚苯乙烯降解微生物以及鉴定潜在的聚苯乙烯生物降解酶。在此基础上,我们提出了潜在的 PS 生物降解途径,尽管与某些酶相关的具体生化机制尚未完全确定。最后,我们讨论了如何利用基于系统生物学的筛选方法来鉴定 PS 生物降解酶,该方法结合了基于培养的基因组学和不依赖培养的元基因组学方法。这种策略可用于寻找其他塑料的生物降解酶。
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引用次数: 0
Capped or uncapped? Techniques to assess the quality of mRNA molecules 有封顶还是无封顶?评估 mRNA 分子质量的技术
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-04 DOI: 10.1016/j.coisb.2023.100503
Ying Tu, Akashaditya Das, Chileab Redwood-Sawyerr, Karen M. Polizzi

The successful use of mRNA vaccines during the Covid-19 pandemic has created a boom in mRNA therapeutic research and development. The efficacy of mRNA vaccines and therapies relies on the quality of the synthesized molecules – a key feature of which is the 5′-end cap modification. The development of analytical methods for assessing mRNA quality needs to be prioritized to enable manufacturing development, process control, and rapid assessment of batch quality before release. In this review, we provide an overview of the latest techniques in the analysis of mRNA 5′ capping. We also discuss future possibilities and challenges in quality control of mRNA products at scale.

在 Covid-19 大流行期间,mRNA 疫苗的成功使用掀起了 mRNA 疗法研究与开发的热潮。mRNA 疫苗和疗法的疗效取决于合成分子的质量,其中一个关键特征是 5′端帽修饰。需要优先发展评估 mRNA 质量的分析方法,以便进行生产开发、过程控制和发布前批次质量的快速评估。在本综述中,我们概述了分析 mRNA 5′ 端封帽的最新技术。我们还讨论了大规模 mRNA 产品质量控制的未来可能性和挑战。
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引用次数: 0
Synthetic interventions in epigenome: Unraveling chromatin's potential for therapeutic applications 表观基因组的合成干预:揭示染色质的治疗应用潜力
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-03 DOI: 10.1016/j.coisb.2023.100504
Junyoung Kim , Jonghyun Kim , Minhee Park

The epigenome, comprising DNA and histone modifications alongside intricate chromatin structures, has emerged as pivotal players in disease development. These factors offer promising opportunities for therapeutic interventions, expanding the avenues traditionally explored within genetic elements. Eukaryotic chromatin exhibits an impressive capacity for computation and information storage, fueled by the dynamic interplay of factors that modify the physicochemical states of chromatin. With its unique attributes, chromatin emerges as a compelling candidate for synthetic intervention and therapeutic reprogramming. In this review, we explore pioneering initiatives aimed at synthetically manipulating the epigenome, a relatively uncharted domain with transformative potential for both diagnostics and treatments.

表观基因组包括 DNA 和组蛋白修饰以及错综复杂的染色质结构,已成为疾病发展的关键因素。这些因素为治疗干预提供了大好机会,拓展了传统上在遗传因子中探索的途径。真核染色质在改变染色质理化状态的各种因素的动态相互作用下,表现出惊人的计算和信息存储能力。染色质具有独特的属性,是合成干预和治疗重编程的理想候选对象。在这篇综述中,我们将探讨旨在综合操纵表观基因组的开创性计划,这是一个相对未知的领域,在诊断和治疗方面都具有变革潜力。
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引用次数: 0
Microbial cell factories for bio-based isoprenoid production to replace fossil resources 用于生产生物基异戊二烯以替代化石资源的微生物细胞工厂
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-01-03 DOI: 10.1016/j.coisb.2023.100502
Min-Kyoung Kang , Sang-Hwal Yoon , Moonhyuk Kwon , Seon-Won Kim

Concerns about environmental issues and limited fossil resources have increased interest and efforts in developing sustainable production of bio-based chemicals and fuels using microorganisms. Advanced metabolic engineering has developed microbial cell factories (MCFs) with the support of synthetic biology and systems biology. Isoprenoids are one of the largest classes of natural products and possess many practical industrial applications. However, it is challenging to meet the market demand for isoprenoids because of the current inefficient and unsustainable strategies for isoprenoid production such as chemical synthesis and plant extraction. Therefore, many efforts have been made to build isoprenoid-producing MCFs by applying metabolic engineering strategies, biological devices, and machinery from synthetic biology and systems biology. This review introduces recent studies of strain engineering and applications of biological tools and systems for developing isoprenoid MCFs. In addition, we also reviewed the isoprenoid fermentation strategies that lead to the best performance of isoprenoid-producing MCFs.

对环境问题和有限化石资源的关注,提高了人们对利用微生物开发可持续生产生物基化学品和燃料的兴趣和努力。在合成生物学和系统生物学的支持下,先进的代谢工程开发出了微生物细胞工厂(MCF)。异戊烯类化合物是最大类的天然产品之一,具有许多实际的工业应用。然而,由于目前的异戊烯类化合物生产策略(如化学合成和植物提取)效率低下且不可持续,因此要满足市场对异戊烯类化合物的需求具有挑战性。因此,人们已经做出许多努力,通过应用合成生物学和系统生物学中的代谢工程策略、生物装置和机器来构建生产异戊二烯的 MCF。本综述介绍了最近在开发异戊二烯 MCFs 的菌株工程和生物工具及系统应用方面的研究。此外,我们还综述了能使生产异戊烯类化合物的 MCF 达到最佳性能的异戊烯类化合物发酵策略。
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引用次数: 0
From sequence to function and back – High-throughput sequence-function mapping in synthetic biology 从序列到功能再到序列--合成生物学中的高通量序列功能图谱
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-13 DOI: 10.1016/j.coisb.2023.100499
Simon Höllerer , Charlotte Desczyk , Ricardo Farrera Muro , Markus Jeschek

How does genetic sequence give rise to biological function? Answering this question is key to our understanding of life and the construction of synthetic biosystems that fight disease, resource scarcity and climate change. Unfortunately, the virtually infinite number of possible sequences and limitations in their functional characterization limit our current understanding of sequence-function relationships. To overcome this dilemma, several high-throughput methods to experimentally link sequences to corresponding functional properties have been developed recently. While all of these share the goal to collect sequence-function data at large scale, they differ significantly in their technical approach, functional readout and application scope. Herein, we highlight recent developments in the aspiring field of high-throughput sequence-function mapping providing a critical assessment of their potential in synthetic biology.

基因序列如何产生生物功能?回答这个问题是我们了解生命、构建合成生物系统以对抗疾病、资源匮乏和气候变化的关键。遗憾的是,可能存在的序列数量几乎无穷无尽,而其功能表征却存在局限性,这限制了我们目前对序列-功能关系的理解。为了克服这一困境,最近开发了几种高通量方法,通过实验将序列与相应的功能特性联系起来。虽然所有这些方法的共同目标都是大规模收集序列-功能数据,但它们在技术方法、功能读出和应用范围上有很大不同。在此,我们将重点介绍高通量序列-功能图谱这一令人向往的领域的最新进展,并对其在合成生物学中的潜力进行批判性评估。
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引用次数: 0
Accelerate acetogenic bioproduction: Acetogens as sustainable producers of biocommodities 加速醋酸生物生产:作为可持续生物商品生产者的产酸菌
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-12 DOI: 10.1016/j.coisb.2023.100500
Maximilian Flaiz , Diana Z. Sousa

Gas fermentation using autotrophic acetogenic bacteria has been industrialized, however, its full potential remains untapped, with only native products like ethanol being produced thus far. Advancements in synthetic biology have enabled the recombinant production of diverse biocommodities to broaden their limited natural product spectrum from C1-gases. Additionally, co-culturing acetogens with other microorganisms holds the potential for expanding the product spectrum further. However, commercialization remains challenging due to complex pathway and (co)culturing optimizations. To address this, novel synthetic biology tools, including the use of high throughput biopart screenings using reporter proteins, the deployment of cell-free systems to combine best-performing enzymes, and the identification and elimination of competing pathways, can be employed. Incorporating genetically engineered strains in co-cultures improves dependencies, directs product formation, and increases resilience, enhancing bioproduction efficiency. This review emphasizes using these tools to enhance the recombinant production of biocommodities, offering promising solutions to overcome existing challenges.

利用自养醋酸菌进行气体发酵已经实现了工业化,但其全部潜力仍未开发,迄今只能生产乙醇等本地产品。合成生物学的进步使得重组生产多种生物商品成为可能,从而扩大了 C1 气体的有限天然产品范围。此外,与其他微生物共同培养乙炔原也有可能进一步扩大产品范围。然而,由于复杂的途径和(共)培养优化,商业化仍具有挑战性。为解决这一问题,可采用新型合成生物学工具,包括使用报告蛋白进行高通量生物部分筛选、部署无细胞系统以组合性能最佳的酶,以及识别和消除竞争途径。在共培养物中加入基因工程菌株可改善依赖性、指导产品的形成并提高复原力,从而提高生物生产效率。本综述强调利用这些工具来提高生物商品的重组生产,为克服现有挑战提供有前景的解决方案。
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引用次数: 0
Cell-free systems and genetic biosensors for accelerating enzyme and pathway prototyping 加速酶和通路原型开发的无细胞系统和基因生物传感器
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-10 DOI: 10.1016/j.coisb.2023.100501
Wonhee Kim , Sohun Lee , Bong Hyun Sung , Jeong-Geol Na , Jeong Wook Lee

Integration of cell-free systems with genetic biosensors is emerging as an advantageous platform for small molecule detection. This biosensor-coupled cell-free system simplifies an assay-and-detection procedure by combining the advantages of rapid and efficient protein expression through a cell-free system and the in situ detection capabilities provided by genetic biosensors. Moreover, this system is easy to assay multiple conditions at once, as the open environment of the cell-free systems enhances overall ease of handling. In this review, we focus on the acceleration of enzyme and pathway prototyping using cell-free biosensors, as well as strategies to improve the sensitivity and specificity of biosensors. High-throughput screening tools that can expand the prototyping process by generating massive data sets for rapid evaluation were also described.

无细胞系统与基因生物传感器的整合正在成为小分子检测的有利平台。这种生物传感器耦合无细胞系统结合了无细胞系统快速高效表达蛋白质的优势和基因生物传感器提供的原位检测能力,简化了化验和检测程序。此外,由于无细胞系统的开放环境提高了整体操作的简便性,因此该系统易于同时检测多种条件。在本综述中,我们将重点讨论利用无细胞生物传感器加速酶和通路原型开发,以及提高生物传感器灵敏度和特异性的策略。此外还介绍了高通量筛选工具,这些工具可以通过生成大量数据集来快速评估,从而扩展原型开发过程。
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引用次数: 0
Designing microbial cell factories for programmable control of cellular metabolism 设计可编程控制细胞代谢的微生物细胞工厂
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-04 DOI: 10.1016/j.coisb.2023.100493
Soo Young Moon , So-Hee Son , Seung-Ho Baek , Ju Young Lee

Synthetic biology has promoted a conceptual shift in metabolic engineering for the microbial production of industrial chemicals toward a sustainable economy. Engineering principles from synthetic biology and metabolic engineering are integrated to redesign cellular metabolism to create microbial cell factories with emerging and programmable functionalities. Combining metabolic engineering with programmed spatial control is a promising approach that enables deep rewiring of microbial cell factory metabolism for the efficient production of bio-based chemicals. In this review, we discuss metabolic compartmentalization approaches for programmable control of cellular metabolism, including intracellular or intercellular partitioning-based organization of biosynthetic pathways. We also examine the designs and applications of cellular compartments and their analogs, highlighting selected examples for creating efficient and sustainable microbial cell factories.

合成生物学促进了代谢工程概念的转变,使工业化学品的微生物生产朝着可持续经济的方向发展。合成生物学的工程原理与代谢工程相结合,重新设计细胞代谢,创建具有新兴和可编程功能的微生物细胞工厂。将代谢工程与程序化空间控制相结合是一种很有前景的方法,它能深度重构微生物细胞工厂的新陈代谢,从而高效生产生物基化学品。在本综述中,我们将讨论可编程控制细胞代谢的代谢分区方法,包括基于细胞内或细胞间分区的生物合成途径组织。我们还研究了细胞区室及其类似物的设计和应用,重点介绍了用于创建高效、可持续微生物细胞工厂的部分实例。
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引用次数: 0
Editorial Board Page 编辑委员会页面
IF 3.7 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2023-12-01 DOI: 10.1016/S2452-3100(23)00052-5
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引用次数: 0
期刊
Current Opinion in Systems Biology
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