Engineering Microbiology最新文献

英文中文

Erratum to “In vitro characterization of a nitro-forming oxygenase involved in 3-(trans-2’-aminocyclopropyl)alanine biosynthesis” [Engineering Microbiology 2 (2022) 100007] 对“参与3-（反式-2 ' -氨基环丙基）丙氨酸生物合成的一种造氮加氧酶的体外表征”的勘误[工程微生物学2 (2022)100007]

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2025-03-13 DOI: 10.1016/j.engmic.2025.100195

Linlin Pang , Weijing Niu , Yuwei Duan , Liujie Huo , Aiying Li , Jiequn Wu , Youming Zhang , Xiaoying Bian , Guannan Zhong

引用次数: 0

Complexity of antibiotic resistance and its impact on gut microbiota dynamics 抗生素耐药性的复杂性及其对肠道菌群动力学的影响

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2024-12-30 DOI: 10.1016/j.engmic.2024.100187

H. Shayista , M.N. Nagendra Prasad , S. Niranjan Raj , Ashwini Prasad , S. Lakshmi , H.K. Ranjini , K. Manju , Ravikumara , Raghuraj Singh Chouhan , Olga Y. Khohlova , Olga V. Perianova , Syed Baker

The present review explores the influence of the gut microbiota on antibiotic resistance dynamics, particularly those associated with dysbiosis. The improper use of antibiotics can induce resistance in pathogens through various pathways, which is a topic of increasing interest within the scientific community. This review highlights the importance of microbial diversity, gut metabolism, and inflammatory responses against the dysbiosis due to the action of antibiotics. Additionally, it examines how secondary metabolites secreted by pathogens can serve as biomarkers for the early detection of antibiotic resistance. Although significant progress has been made in this field, key research gaps persist, including the need for a deeper understanding of the long-term effects of antibiotic-induced dysbiosis and the specific mechanisms driving the evolution of resistance in gut bacteria. Based on these considerations, this review systematically analyzed studies from PubMed, Web of Science, Embase, Cochrane Library, and Scopus up to July 2024. This study aimed to explore the dynamics of the interactions between gut microbiota and antibiotic resistance, specifically examining how microbial composition influences the development of resistance mechanisms. By elucidating these relationships, this review provides insights into management strategies for drug resistance and improves our understanding of microbial contributions to host health.

本综述探讨了肠道微生物群对抗生素耐药性动态的影响，特别是与生态失调有关的影响。抗生素的不当使用可通过多种途径诱导病原体产生耐药性，这是科学界日益关注的一个话题。这篇综述强调了微生物多样性、肠道代谢和炎症反应对抗生素作用引起的生态失调的重要性。此外，它还研究了病原体分泌的次生代谢物如何作为抗生素耐药性早期检测的生物标志物。尽管在这一领域取得了重大进展，但关键的研究差距仍然存在，包括需要更深入地了解抗生素诱导的生态失调的长期影响以及驱动肠道细菌耐药性进化的具体机制。基于这些考虑，本综述系统分析了PubMed、Web of Science、Embase、Cochrane Library和Scopus截至2024年7月的研究。本研究旨在探讨肠道微生物群与抗生素耐药性之间相互作用的动力学，特别是研究微生物组成如何影响耐药性机制的发展。通过阐明这些关系，本综述为耐药管理策略提供了见解，并提高了我们对微生物对宿主健康贡献的理解。

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引用次数: 0

Activating cryptic biosynthetic gene clusters via ACTIMOT 通过ACTIMOT激活隐生生物合成基因簇

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2025-01-24 DOI: 10.1016/j.engmic.2025.100190

Xiaoying Bian

The mainstream strategy of genome mining relies on the homologous activation and heterologous expression of target biosynthetic gene clusters (BGCs). However, the efficiency of the current techniques available for new compound discovery hardly complements these efforts. In a recent publication in Science, Xie et al. reported their breakthrough progress in expediting the discovery of untapped chemical diversity from bacteria by establishing the leveraged know-how of ACTIMOT (Advanced Cas9-mediaTed In vivo MObilization and mulTiplication of BGCs), offering a new avenue to access the unexploited, and even unpredictable, biosynthetic potential of bacteria.

基因组挖掘的主流策略依赖于目标生物合成基因簇（BGCs）的同源激活和异源表达。然而，现有的新化合物发现技术的效率很难弥补这些努力。在最近发表在《科学》杂志上的一篇文章中，Xie等人报道了他们通过建立ACTIMOT（高级cas9介导的bgc体内动员和增殖）的利用技术，在加速发现细菌未开发的化学多样性方面取得的突破性进展，为挖掘细菌未开发的、甚至不可预测的生物合成潜力提供了新的途径。

引用次数: 0

Characterization of a small non-coding RNA S612 in Bacillus subtilis 枯草芽孢杆菌非编码小RNA S612的鉴定

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2024-12-09 DOI: 10.1016/j.engmic.2024.100186

Anqi Peng , Weijiao Zhang , Haibo Xiong , Luyao Zhang , Jian Cheng , Yang Wang , Zhen Kang

Small regulatory RNAs (sRNAs) are non-coding RNA molecules that fine-tune various cellular processes and respond to various environmental stimuli. In Bacillus subtilis, the regulatory mechanisms and specific targets of several sRNAs remain largely unknown. In this study, we identified and characterized S612 as a self-terminating sRNA in B. subtilis. The expression of S612 is regulated by external signals, including nutrient availability and salt concentration. Overexpression of S612 induced filamentous cells with extensive cellular elongation and complete inhibition of sporulation, indicating its potential to control cell morphology and spore formation. S612 directly targets and downregulates genes through post-transcriptional base pairing with mRNAs, including ylmD, trpE, ycxC, yycS, rapH, and amyE, some of which are involved in cell membrane integrity, cell wall synthesis, and sporulation initiation. Therefore, we propose that S612 is an important post-transcriptional regulator of cell morphology and sporulation.

小调控RNA （Small regulatory RNA, sRNAs）是一种非编码RNA分子，可以对各种细胞过程进行微调，并对各种环境刺激做出反应。在枯草芽孢杆菌中，几种srna的调控机制和特定靶点在很大程度上仍然未知。在这项研究中，我们鉴定并鉴定了S612是枯草芽孢杆菌中一个自终止的sRNA。S612的表达受外界信号的调控，包括养分有效性和盐浓度。过表达S612诱导的丝状细胞具有广泛的细胞伸长和孢子形成的完全抑制，表明其具有控制细胞形态和孢子形成的潜力。S612通过与mrna的转录后碱基配对直接靶向和下调基因，包括ylmD、trpE、ycxC、yycS、rapH和amyE，其中一些基因参与细胞膜完整性、细胞壁合成和孢子形成起始。因此，我们认为S612是细胞形态和孢子形成的重要转录后调节因子。

引用次数: 0

Establishment and improvement of genetic manipulation tools for Fusobacterium nucleatum 核梭杆菌基因操作工具的建立与改进

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2025-02-08 DOI: 10.1016/j.engmic.2025.100192

Zhiwei Guan , Hailong Wang , Qiang Feng

An imbalance in oral microbial homeostasis is significantly associated with the onset and progression of several systemic diseases. Fusobacterium nucleatum, a ubiquitous periodontitis-causing bacterium in the oral cavity, is frequently detected in focal sites and contributes to the pathogenesis of many extraoral diseases, including cancers, cardiovascular diseases, and adverse pregnancy outcomes (APOs). F. nucleatum is one of the few oral anaerobes that can be cultured purely in vitro and is a ‘model species’ for studying the impact of oral health on systemic health. The establishment and development of genetic manipulation tools for F. nucleatum and the construction of pathogenic gene-disrupted strains are important strategies for studying the pathogenicity of F. nucleatum. Here, we review the establishment and development of the genetic manipulation systems for F. nucleatum and summarize the characteristics of various genetic manipulation tools, such as suicide plasmid-based systems for gene inactivation, replicable plasmid-based systems controlling gene expression, and transposon-based random mutagenesis systems. Notably, we summarize and analyze their applications in the study of the pathogenic mechanisms of F. nucleatum. We hope to provide reference information and ideas for future research on genetic manipulation tools and the pathogenic mechanisms of F. nucleatum and other Fusobacterium species.

口腔微生物稳态失衡与几种全身性疾病的发生和进展密切相关。核梭杆菌是口腔中普遍存在的引起牙周炎的细菌，经常在病灶部位检测到，并有助于许多口外疾病的发病机制，包括癌症、心血管疾病和不良妊娠结局（APOs）。具核梭菌是少数可以在体外培养的口腔厌氧菌之一，是研究口腔健康对全身健康影响的“模式物种”。建立和开发核仁梭菌遗传操作工具，构建致病基因破坏菌株是研究核仁梭菌致病性的重要策略。本文综述了核仁梭菌遗传操作系统的建立和发展，并总结了各种遗传操作工具的特点，如基于自杀质粒的基因失活系统、基于可复制质粒的基因表达控制系统和基于转座子的随机诱变系统。值得注意的是，我们总结和分析了它们在研究具核梭菌致病机制中的应用。希望为今后研究具核梭菌和其他梭菌的遗传操作工具和致病机制提供参考信息和思路。

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引用次数: 0

Terminal deoxynucleotidyl transferase: Properties and applications 末端脱氧核苷酸转移酶：性质与应用

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2024-11-28 DOI: 10.1016/j.engmic.2024.100179

Chengjie Zhang , Hizar Subthain , Fei Guo , Peng Fang , Shanmin Zheng , Mengzhe Shen , Xianger Jiang , Zhengquan Gao , Chunxiao Meng , Shengying Li , Lei Du

Terminal deoxynucleotidyl transferase (TdT), a unique DNA polymerase, can elongate DNA by adding deoxynucleotides to the 3′ terminal of a DNA chain in a template-independent manner. Owing to their remarkable DNA synthesis activity, TdTs have promoted the development of numerous nucleic acid-based methods, tools, and associated applications, attracting broad interest from both academia and industry. This review summarizes and discusses the recent research on TdTs, including their biochemical characteristics, enzyme engineering, and practical applications. New insights and perspectives on the future development of TdTs are provided.

末端脱氧核苷酸转移酶（TdT）是一种独特的DNA聚合酶，它可以以模板无关的方式将脱氧核苷酸添加到DNA链的3 '端，从而延长DNA。由于其显著的DNA合成活性，tdt促进了许多基于核酸的方法、工具和相关应用的发展，引起了学术界和工业界的广泛兴趣。本文综述了近年来tdt的研究进展，包括tdt的生化特性、酶工程和实际应用。对tdt的未来发展提出了新的见解和观点。

引用次数: 0

The gut virome and human health: From diversity to personalized medicine 肠道病毒与人类健康：从多样性到个性化医疗

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2025-02-07 DOI: 10.1016/j.engmic.2025.100191

Rahul Harikumar Lathakumari, Leela Kakithakara Vajravelu, Anusha Gopinathan, Poornima Baskar Vimala, Vishnupriya Panneerselvam, Sujith Sri Surya Ravi, Jayaprakash Thulukanam

The human gut virome plays a crucial role in the gut and overall health; its diversity and regulatory functions influence bacterial populations, metabolism, and immune responses. Bacteriophages (phages) and eukaryotic viruses within the gut microbiome contribute to these processes, and recent advancements in sequencing technologies and bioinformatics have greatly expanded our understanding of the gut virome. These advances have led to the development of phage-based therapeutics, diagnostics, and artificial intelligence-driven precision medicine. The emerging field of phageomics shows promise for delivering personalized phage therapies that combat antimicrobial resistance by specifically targeting pathogenic bacteria while preserving beneficial microbes. Moreover, CRISPR-Cas systems delivered via phages have shown success in selectively targeting antibiotic resistance genes and enhancing treatment effectiveness. Phage-based diagnostics are highly sensitive in detecting bacterial pathogens, offering significant benefits for human health and zoonotic disease surveillance. This synthesis of the current knowledge highlights the pivotal role of the gut virome in regulating microbial communities and its transformative potential in personalized medicine, emphasizing its importance in advancing therapeutic and diagnostic strategies for improving health outcomes.

人类肠道病毒组在肠道和整体健康中起着至关重要的作用；其多样性和调控功能影响细菌种群、代谢和免疫反应。肠道微生物组中的噬菌体（噬菌体）和真核病毒有助于这些过程，最近测序技术和生物信息学的进展大大扩展了我们对肠道病毒组的理解。这些进步导致了基于噬菌体的治疗、诊断和人工智能驱动的精准医学的发展。新兴的噬菌体领域显示出提供个性化噬菌体疗法的希望，通过特异性靶向致病菌来对抗抗菌素耐药性，同时保留有益微生物。此外，通过噬菌体传递的CRISPR-Cas系统在选择性靶向抗生素耐药基因和提高治疗效果方面取得了成功。基于噬菌体的诊断在检测细菌病原体方面非常敏感，为人类健康和人畜共患疾病监测提供了重大益处。这种对当前知识的综合强调了肠道病毒组在调节微生物群落方面的关键作用及其在个性化医疗中的变革潜力，强调了其在推进治疗和诊断策略以改善健康结果方面的重要性。

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引用次数: 0

Engineering Microbiology

Pub Date : 2025-03-01 Epub Date: 2025-01-01 DOI: 10.1016/j.engmic.2024.100188

Zhiwei Deng, Zhenbo Yuan, Zhengshan Luo, Yijian Rao

Owing to their diverse coordination patterns and catalytic mechanisms, non-heme iron-dependent dioxygenases catalyze a variety of biochemical reactions involved in the synthesis of numerous natural products and valuable compounds. Recently, we discovered a novel and atypical non-heme iron-dependent dioxygenase, BTG13, that features a unique coordination center consisting of four histidines and a carboxylated lysine (Kcx). This enzyme catalyzes the C–C bond cleavage of anthraquinone through two unconventional steps, with modified Kcx playing a key role in facilitating these processes, as revealed by molecular dynamics simulations and quantum chemical calculations. Phylogenetic analyses and other studies suggest that BTG13-related metalloenzymes are widespread in various organisms. Here, we highlight the significance of this new class of non-heme iron-dependent oxygenases and their potential as novel tools for practical applications in synthetic biology.

非血红素铁依赖性双加氧酶由于其不同的配位模式和催化机制，催化多种生物化学反应，参与许多天然产物和有价值化合物的合成。最近，我们发现了一种新的非典型非血红素铁依赖性双加氧酶BTG13，它具有一个独特的配位中心，由四个组氨酸和一个羧化赖氨酸（Kcx）组成。分子动力学模拟和量子化学计算表明，该酶通过两个非常规步骤催化蒽醌的C-C键裂解，改性的Kcx在促进这一过程中发挥了关键作用。系统发育分析和其他研究表明，btg13相关的金属酶广泛存在于各种生物中。在这里，我们强调了这类新的非血红素铁依赖加氧酶的重要性，以及它们作为合成生物学实际应用的新工具的潜力。

引用次数: 0

Genetically engineered bacteria as inflammatory bowel disease therapeutics 作为炎症性肠病疗法的基因工程细菌

Engineering Microbiology

Pub Date : 2024-12-01 Epub Date: 2024-09-01 DOI: 10.1016/j.engmic.2024.100167

Zhen-Ping Zou , Xiao-Peng Zhang , Qian Zhang, Bin-Cheng Yin, Ying Zhou, Bang-Ce Ye

Inflammatory bowel disease (IBD) is a chronic and recurrent disease caused by immune response disorders that disrupt the intestinal lumen symbiotic ecosystem and dysregulate mucosal immune functions. Current therapies available for IBD primarily focus on symptom management, making early diagnosis and prompt intervention challenging. The development of genetically engineered bacteria using synthetic biology presents a new strategy for addressing these challenges. In this review, we present recent breakthroughs in the field of engineered bacteria for the treatment and detection of IBD and describe how bacteria can be genetically modified to produce therapeutic molecules or execute diagnostic functions. In particular, we discuss the challenges faced in translating live bacterial therapeutics from bacterial design to delivery strategies for further clinical applications.

炎症性肠病（IBD）是一种慢性复发性疾病，由免疫反应紊乱引起，破坏了肠腔共生生态系统，并导致粘膜免疫功能失调。目前治疗 IBD 的疗法主要集中于症状控制，因此早期诊断和及时干预具有挑战性。利用合成生物学开发基因工程细菌为应对这些挑战提供了一种新策略。在这篇综述中，我们介绍了用于治疗和检测 IBD 的工程细菌领域的最新突破，并描述了如何对细菌进行基因改造，使其产生治疗分子或执行诊断功能。我们特别讨论了将活细菌疗法从细菌设计转化为进一步临床应用的递送策略所面临的挑战。

引用次数: 0

Immobilization of Thermomyces lanuginosus lipase on metal-organic frameworks and investigation of their catalytic properties and stability 在金属有机框架上固定热霉菌脂肪酶并研究其催化特性和稳定性

Engineering Microbiology

Pub Date : 2024-12-01 Epub Date: 2024-10-28 DOI: 10.1016/j.engmic.2024.100176

Zeynab Rangraz , Mostafa M. Amini , Zohreh Habibi

Surface adsorption is a convenient and readily available method for immobilizing enzymes on metal-organic frameworks (MOFs). Metal-organic framework-5 (MOF-5), isoreticular metal-organic frameworks-3 (IRMOF-3), and multivariate analysis of MOF-5/IRMOF-3 (MMI) with a half-amino group (-NH₂) were prepared in this study. Thermomyces lanuginosus lipase (TLL) was chosen as a commercially available enzyme for immobilization on the surfaces of these MOFs. Briefly, 1.5 mg of TLL was added to 10 mg of the MOFs, and after 24 h, 67, 74, and 88% of the TLL was immobilized on MOF-5, IRMOF-3, and MMI, respectively. Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, energy-dispersive X-ray analysis, and Brunauer–Emmett–Teller analysis were used to characterize the resulting biocomposites. TLL@MOF-5, TLL@IRMOF-3, and TLL@MMI exhibited activities of 55, 75, and 110 U/mg, respectively. Investigation of the activity and stability of the prepared biocatalysts showed that TLL immobilized on MMI was 2.34-fold more active than free TLL. TLL@MMI exhibited high stability and activity even under harsh conditions. After 24 h of incubation in a mixture of 50% (v/v) MeOH, TLL@MMI retained 80% of its activity, whereas TLL@MOF-5 and free TLL lost 50 and 60% of their activities, respectively. TLL@MMI was used to synthesize 2-arylidenehydrazinyl-4-arylthiozole derivatives (91–98%) in a one-pot vessel by adding benzaldehydes, phenacyl bromides, and thiosemicarbazide to water. The efficiency of the 4a derivative with free TLL was 43%, whereas that with TLL@MMI was 98%.

表面吸附是将酶固定在金属有机框架（MOFs）上的一种方便易得的方法。本研究制备了金属有机框架-5（MOF-5）、等规金属有机框架-3（IRMOF-3）以及带有半氨基（-NH2）的MOF-5/IRMOF-3（MMI）的多元分析。热酵母脂肪酶（TLL）被选为固定在这些 MOF 表面的市售酶。简单地说，将 1.5 毫克 TLL 加入 10 毫克 MOF，24 小时后，分别有 67%、74% 和 88% 的 TLL 被固定在 MOF-5、IRMOF-3 和 MMI 上。傅立叶变换红外光谱、X 射线衍射、热重分析、扫描电子显微镜、能量色散 X 射线分析和布鲁瑙尔-艾美特-泰勒分析被用来表征所得到的生物复合材料。TLL@MOF-5、TLL@IRMOF-3 和 TLL@MMI 的活性分别为 55、75 和 110 U/mg 。对所制备的生物催化剂的活性和稳定性的研究表明，固定在 MMI 上的 TLL 的活性是游离 TLL 的 2.34 倍。即使在苛刻的条件下，TLL@MMI 也表现出很高的稳定性和活性。在 50%（v/v）MeOH 混合液中培养 24 小时后，TLL@MMI 保持了 80% 的活性，而 TLL@MOF-5 和游离 TLL 则分别丧失了 50% 和 60% 的活性。将 TLL@MMI 加入苯甲醛、苯基溴化物和硫代氨基甲酰肼水溶液中，在一锅容器中合成了 2-芳基肼基-4-芳基硫唑衍生物（91-98%）。使用游离 TLL 的 4a 衍生物的效率为 43%，而使用 TLL@MMI 的效率为 98%。

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