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Veillonella parvula promotes root caries development through interactions with Streptococcus mutans and Candida albicans 伞菌 Veillonella 通过与变异链球菌和白色念珠菌相互作用,促进龋齿根的发展。
IF 5.7 2区 生物学 Pub Date : 2024-08-19 DOI: 10.1111/1751-7915.14547
Guo Li, Yuqiu Liu, Mengdie Zhang, Jia Ning, Linrui Wu, Lixiang Jian, Hongkun Wu, Xingqun Cheng

Root caries is a subtype of dental caries that predominantly impacts older adults. The occurrence and progression of root caries are associated with the homeostasis of dental plaque biofilm, and microbial synergistic and antagonistic interactions in the biofilm play a significant role in maintaining the oral microecological balance. The objective of the current study was to investigate the role of Veillonella parvula in the microbial interactions and the pathogenesis of root caries. The analysis of clinical samples from patients with/without root caries revealed that Veillonella and V. parvula were abundant in the saliva of patients with root caries. More importantly, a significantly increased colonization of V. parvula was observed in root carious lesions. Further in vitro biofilm and animal study showed that V. parvula colonization increased the abundance and virulence of Streptococcus mutans and Candida albicans, leading to the formation of a polymicrobial biofilm with enhanced anti-stress capacity and cariogenicity, consequently exacerbating the severity of carious lesions. Our results indicate the critical role of V. parvula infection in the occurrence of root caries, providing a new insight for the etiological investigation and prevention of root caries.

根龋是龋齿的一种亚型,主要影响老年人。根龋的发生和发展与牙菌斑生物膜的平衡有关,而生物膜中微生物的协同和拮抗作用在维持口腔微生态平衡方面发挥着重要作用。本研究的目的是探讨副龈上维氏菌在微生物相互作用和根龋发病机制中的作用。对患有/未患有根龋的患者的临床样本进行分析后发现,根龋患者唾液中含有大量的Veillonella和V. parvula。更重要的是,在根部龋坏病灶中观察到副噬菌体的定植率明显增加。进一步的体外生物膜和动物研究表明,副龈弧菌的定植增加了变异链球菌和白色念珠菌的数量和毒力,从而形成了抗应激能力和致龋性更强的多微生物生物膜,从而加剧了龋病的严重程度。我们的研究结果表明,V. parvula 感染在根龋的发生中起着至关重要的作用,这为根龋的病因学研究和预防提供了新的视角。
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引用次数: 0
Bacterial synthesis of metal nanoparticles as antimicrobials 细菌合成金属纳米颗粒作为抗菌剂。
IF 5.7 2区 生物学 Pub Date : 2024-08-16 DOI: 10.1111/1751-7915.14549
Anika Arora, Elham Lashani, Raymond J. Turner

Nanoscience, a pivotal field spanning multiple industries, including healthcare, focuses on nanomaterials characterized by their dimensions. These materials are synthesized through conventional chemical and physical methods, often involving costly and energy-intensive processes. Alternatively, biogenic synthesis using bacteria, fungi, or plant extracts offers a potentially sustainable and non-toxic approach for producing metal-based nanoparticles (NP). This eco-friendly synthesis approach not only reduces environmental impact but also enhances features of NP production due to the unique biochemistry of the biological systems. Recent advancements have shown that along with chemically synthesized NPs, biogenic NPs possess significant antimicrobial properties. The inherent biochemistry of bacteria enables the efficient conversion of metal salts into NPs through reduction processes, which are further stabilized by biomolecular capping layers that improve biocompatibility and functional properties. This mini review explores the use of bacteria to produce NPs with antimicrobial activities. Microbial technologies to produce NP antimicrobials have considerable potential to help address the antimicrobial resistance crisis, thus addressing critical health issues aligned with the United Nations Sustainability Goal #3 of good health and well-being.

纳米科学是一个横跨多个行业(包括医疗保健)的关键领域,主要研究以尺寸为特征的纳米材料。这些材料是通过传统的化学和物理方法合成的,通常涉及高成本和高能耗的过程。另外,利用细菌、真菌或植物提取物进行生物合成,为生产金属基纳米粒子(NP)提供了一种潜在的可持续和无毒的方法。这种生态友好型合成方法不仅减少了对环境的影响,而且由于生物系统独特的生物化学特性,还增强了 NP 生产的功能。最新进展表明,除了化学合成的 NP 外,生物 NP 也具有显著的抗菌特性。细菌固有的生物化学特性使其能够通过还原过程将金属盐高效转化为 NPs,并通过生物分子封盖层进一步稳定 NPs,从而改善其生物相容性和功能特性。这篇微型综述探讨了利用细菌生产具有抗菌活性的 NPs。生产 NP 抗菌剂的微生物技术具有相当大的潜力,有助于解决抗菌剂耐药性危机,从而解决与联合国可持续发展目标 3 健康和福祉相一致的关键健康问题。
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引用次数: 0
Green microbes: Potential solutions for key sustainable development goals 绿色微生物:主要可持续发展目标的潜在解决方案。
IF 5.7 2区 生物学 Pub Date : 2024-08-10 DOI: 10.1111/1751-7915.14546
Sandra Diaz-Troya, María José Huertas

The latest assessment of progress towards the Sustainable Development Goals (SDGs) has identified major obstacles, such as climate change, global instability and pandemics, which threaten efforts to achieve the SDGs even by 2050. Urgent action is needed, particularly to reduce poverty, hunger and climate change. In this context, microalgae are emerging as a promising solution, particularly in the context of food security and environmental sustainability. As versatile organisms, microalgae offer nutritional benefits such as high-quality proteins and essential fatty acids, and can be cultivated in non-arable areas, reducing competition for resources and improving the sustainability of food systems. The role of microalgae also includes other applications in aquaculture, where they serve as sustainable alternatives to animal feed, and in agriculture, where they act as biofertilizers and biostimulants. These microorganisms also play a key role in interventions on degraded land, stabilizing soils, improving hydrological function and increasing nutrient and carbon availability. Microalgae therefore support several SDGs by promoting sustainable agricultural practices and contributing to land restoration and carbon sequestration efforts. The integration of microalgae in these areas is essential to mitigate environmental impacts and improve global food security, highlighting the need for increased research and development, as well as public and political support, to exploit their full potential to advance the SDGs.

对实现可持续发展目标(SDGs)进展情况的最新评估发现,气候变化、全球不稳定和流行病等重大障碍甚至威胁到到 2050 年实现可持续发展目标的努力。需要采取紧急行动,特别是减少贫困、饥饿和气候变化。在此背景下,微藻正成为一种前景广阔的解决方案,尤其是在粮食安全和环境可持续性方面。作为多用途生物,微藻具有优质蛋白质和必需脂肪酸等营养价值,而且可以在非可耕地种植,从而减少对资源的争夺,提高粮食系统的可持续性。微藻的作用还包括在水产养殖和农业中的其他应用,前者是动物饲料的可持续替代品,后者则是生物肥料和生物刺激剂。这些微生物在干预退化土地、稳定土壤、改善水文功能以及增加养分和碳供应方面也发挥着关键作用。因此,微藻通过促进可持续农业实践、推动土地恢复和碳固存努力,支持多项可持续发展目标。将微藻类纳入这些领域对于减轻环境影响和提高全球粮食安全至关重要,这凸显了加强研究与开发以及公共和政治支持的必要性,以充分挖掘微藻类的潜力,推动可持续发展目标的实现。
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引用次数: 0
Into the metabolic wild: Unveiling hidden pathways of microbial metabolism 进入新陈代谢的狂野揭开微生物新陈代谢的隐秘途径。
IF 5.7 2区 生物学 Pub Date : 2024-08-10 DOI: 10.1111/1751-7915.14548
Özge Ata, Diethard Mattanovich

Microbial metabolism has been deeply studied over decades and it is considered to be understood to a great extent. Annotated genome sequences of many microbial species have contributed a lot to generating biochemical knowledge on metabolism. However, researchers still discover novel pathways, unforeseen reactions or unexpected metabolites which contradict to the expected canon of biochemical reactions in living organisms. Here, we highlight a few examples of such non-canonical pathways, how they were found, and what their importance in microbial biotechnology may be. The predictive power of metabolic modelling, well-founded on biochemical knowledge and genomic information is discussed in the light of both discovery of yet unknown existing metabolic routes and the prediction of others, new to Nature.

几十年来,人们对微生物的新陈代谢进行了深入研究,并在很大程度上对其有所了解。许多微生物物种的注释基因组序列为新陈代谢生化知识的产生做出了巨大贡献。然而,研究人员仍会发现新的途径、未曾预见的反应或意想不到的代谢物,这些都与生物体内预期的生化反应大纲相悖。在此,我们将重点介绍此类非经典途径的几个实例、它们是如何被发现的,以及它们在微生物生物技术中的重要性。我们从发现未知的现有代谢途径和预测自然界新发现的其他代谢途径的角度,讨论了以生化知识和基因组信息为基础的代谢模型的预测能力。
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引用次数: 0
‘Tiny Biome Tales’: A gamified review about the influence of lifestyle choices on the human microbiome 小小生物群故事关于生活方式选择对人类微生物群影响的游戏化评论。
IF 5.7 2区 生物学 Pub Date : 2024-08-09 DOI: 10.1111/1751-7915.14544
Matthias Schweitzer, Maximilian Wlasak, Birgit Wassermann, Florian Marcher, Christian Poglitsch, Johanna Pirker, Gabriele Berg

In the last two decades, new discoveries from microbiome research have changed our understanding of human health. It became evident that daily habits and lifestyle choices shape the human microbiome and ultimately determine health or disease. Therefore, we developed ‘Tiny Biome Tales’ (https://microbiome.gamelabgraz.at/), a science pedagogy video game designed like a scientific review based exclusively on peer-reviewed articles, to teach about the influence of lifestyle choices on the human microbiome during pregnancy, early and adult life, and related health consequences. Despite the scientific character, it can be played by a broad audience. Here, we also present a scientific assessment and showed that playing the game significantly contributed to knowledge gain. The innovative style of the ‘gamified review’ represents an ideal platform to disseminate future findings from microbiome research by updating existing and adding new scenes to the game.

在过去二十年里,微生物组研究的新发现改变了我们对人类健康的认识。显而易见,日常习惯和生活方式的选择会影响人体微生物组,并最终决定健康或疾病。因此,我们开发了 "Tiny Biome Tales"(https://microbiome.gamelabgraz.at/),这是一款科学教学视频游戏,其设计类似于科学评论,完全基于同行评议的文章,旨在讲授怀孕、早期和成年生活中生活方式的选择对人体微生物组的影响,以及相关的健康后果。尽管该游戏具有科学性,但广大受众也可以玩。在这里,我们还介绍了一项科学评估,结果表明,玩游戏极大地促进了知识的增长。游戏化评论 "的创新风格是一个理想的平台,可以通过更新现有游戏场景和添加新场景来传播微生物组研究的未来成果。
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引用次数: 0
Biopreparations for the decomposition of crop residues 分解作物残留物的生物制剂。
IF 5.7 2区 生物学 Pub Date : 2024-08-07 DOI: 10.1111/1751-7915.14534
Patrycja Rowińska, Beata Gutarowska, Regina Janas, Justyna Szulc

Recently, there has been growing interest in biopreparations that intensify the decomposition of crop residues. These preparations can promote nutrient cycling and soil fertility, ultimately supporting healthy plant growth and increasing agricultural productivity. However, the development and commercialization of biopreparations poses unique challenges. Producers of biopreparations struggle to develop highly effective preparations, which then face regulatory hurdles and must win market acceptance. This literature review provides up-to-date data on microbial preparations available commercially on the European market, along with information on current relevant regulations. Challenges for the development and commercialization of new biopreparations are also discussed. The development and commercialization of biopreparations require a comprehensive approach that addresses the complex interplay of microbial and environmental factors. The need for more specific regulations on biopreparations for decomposing crop residues, clearer instructions on their use, and further research on the overall impact of biopreparations on the soil metabolome and optimal conditions for their application were indicated. Moreover, manufacturers should prioritize the development of high-quality products that meet the needs of farmers and address concerns about environmental impact and public acceptance.

最近,人们对能加强作物残留物分解的生物制剂越来越感兴趣。这些制剂可以促进养分循环和土壤肥力,最终支持植物健康生长并提高农业生产率。然而,生物制剂的开发和商业化带来了独特的挑战。生物制剂的生产商努力开发高效制剂,然后面临监管障碍,还必须赢得市场认可。本文献综述提供了欧洲市场上商业化微生物制剂的最新数据,以及当前相关法规的信息。此外,还讨论了新生物制剂的开发和商业化所面临的挑战。生物制剂的开发和商业化需要一种全面的方法,以解决微生物和环境因素之间复杂的相互作用。会议指出,需要对用于分解作物残留物的生物制剂制定更具体的规定,提供更明确的使用说明,并进一步研究生物制剂对土壤代谢组的总体影响以及最佳应用条件。此外,制造商应优先开发满足农民需求的高质量产品,并解决环境影响和公众接受度方面的问题。
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引用次数: 0
Limiting factors in the operation of photosystems I and II in cyanobacteria 蓝藻光合系统 I 和 II 运行的限制因素。
IF 5.7 2区 生物学 Pub Date : 2024-08-05 DOI: 10.1111/1751-7915.14519
Christen L. Grettenberger, Reda Abou-Shanab, Trinity L. Hamilton

Cyanobacteria are important targets for biotechnological applications due to their ability to grow in a wide variety of environments, rapid growth rates, and tractable genetic systems. They and their bioproducts can be used as bioplastics, biofertilizers, and in carbon capture and produce important secondary metabolites that can be used as pharmaceuticals. However, the photosynthetic process in cyanobacteria can be limited by a wide variety of environmental factors such as light intensity and wavelength, exposure to UV light, nutrient limitation, temperature, and salinity. Carefully considering these limitations, modifying the environment, and/or selecting cyanobacterial species will allow cyanobacteria to be used in biotechnological applications.

蓝藻能够在多种环境中生长,生长速度快,基因系统易于控制,因此是生物技术应用的重要目标。它们及其生物产品可用作生物塑料、生物肥料和碳捕获,并产生可用作药物的重要次级代谢产物。然而,蓝藻的光合作用过程会受到各种环境因素的限制,如光照强度和波长、紫外线照射、营养限制、温度和盐度。仔细考虑这些限制因素、改变环境和/或选择蓝藻物种将使蓝藻能够用于生物技术应用。
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引用次数: 0
Dietary fibre optimisation in support of global health 优化膳食纤维,促进全球健康。
IF 5.7 2区 生物学 Pub Date : 2024-08-03 DOI: 10.1111/1751-7915.14542
Anouschka S. Ramsteijn, Petra Louis

The human gut microbiota influences its host via multiple molecular pathways, including immune system interactions, the provision of nutrients and regulation of host physiology. Dietary fibre plays a crucial role in maintaining a healthy microbiota as its primary nutrient and energy source. Industrialisation has led to a massive decrease of habitual fibre intake in recent times, and fibre intakes across the world are below the national recommendations. This goes hand in hand with other factors in industrialised societies that may negatively affect the gut microbiota, such as medication and increased hygiene. Non-communicable diseases are on the rise in urbanised societies and the optimisation of dietary fibre intake can help to improve global health and prevent disease. Early life interventions shape the developing microbiota to counteract malnutrition, both in the context of industrialised nations with an overabundance of cheap, highly processed foods, as well as in Low- and Middle-Income Countries (LMICs). Adequate fibre intake should, however, be maintained across the life course to promote health. Here we will discuss the current state of dietary fibre research in the global context and consider different intervention approaches.

人体肠道微生物群通过多种分子途径影响宿主,包括免疫系统相互作用、提供营养物质和调节宿主生理机能。膳食纤维作为微生物群的主要营养和能量来源,在维持微生物群健康方面发挥着至关重要的作用。近代以来,工业化导致习惯性纤维摄入量大幅下降,全世界的纤维摄入量都低于国家推荐值。与此同时,工业化社会中的其他因素也可能对肠道微生物群产生负面影响,如药物和卫生条件的改善。非传染性疾病在城市化社会中呈上升趋势,优化膳食纤维摄入量有助于改善全球健康状况和预防疾病。无论是在廉价、高度加工食品过剩的工业化国家,还是在中低收入国家(LMIC),生命早期的干预措施都能塑造发育中的微生物群,从而抵御营养不良。然而,在整个生命过程中都应保持足够的纤维摄入量,以促进健康。在此,我们将讨论全球范围内膳食纤维研究的现状,并考虑不同的干预方法。
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引用次数: 0
Phages produce persisters 噬菌体会产生宿主。
IF 5.7 2区 生物学 Pub Date : 2024-08-03 DOI: 10.1111/1751-7915.14543
Laura Fernández-García, Joy Kirigo, Daniel Huelgas-Méndez, Michael J. Benedik, María Tomás, Rodolfo García-Contreras, Thomas K. Wood

Arguably, the greatest threat to bacteria is phages. It is often assumed that those bacteria that escape phage infection have mutated or utilized phage-defence systems; however, another possibility is that a subpopulation forms the dormant persister state in a manner similar to that demonstrated for bacterial cells undergoing nutritive, oxidative, and antibiotic stress. Persister cells do not undergo mutation and survive lethal conditions by ceasing growth transiently. Slower growth and dormancy play a key physiological role as they allow host phage defence systems more time to clear the phage infection. Here, we investigated how bacteria survive lytic phage infection by isolating surviving cells from the plaques of T2, T4, and lambda (cI mutant) virulent phages and sequencing their genomes. We found that bacteria in plaques can escape phage attack both by mutation (i.e. become resistant) and without mutation (i.e. become persistent). Specifically, whereas T4-resistant and lambda-resistant bacteria with over a 100,000-fold less sensitivity were isolated from plaques with obvious genetic mutations (e.g. causing mucoidy), cells were also found after T2 infection that undergo no significant mutation, retain wild-type phage sensitivity, and survive lethal doses of antibiotics. Corroborating this, adding T2 phage to persister cells resulted in 137,000-fold more survival compared to that of addition to exponentially growing cells. Furthermore, our results seem general in that phage treatments with Klebsiella pneumonia and Pseudomonas aeruginosa also generated persister cells. Hence, along with resistant strains, bacteria also form persister cells during phage infection.

可以说,细菌的最大威胁是噬菌体。人们通常认为,那些躲过噬菌体感染的细菌已经发生变异或利用了噬菌体防御系统;然而,另一种可能性是,有一个亚群形成了休眠持久体状态,其方式类似于细菌细胞在营养、氧化和抗生素压力下的休眠状态。持久细胞不会发生突变,并通过短暂停止生长在致命条件下存活下来。生长缓慢和休眠具有关键的生理作用,因为它们能让宿主噬菌体防御系统有更多时间清除噬菌体感染。在这里,我们通过从 T2、T4 和 lambda(cI 突变体)毒性噬菌体的斑块中分离出存活细胞并对其基因组进行测序,研究了细菌如何在溶解性噬菌体感染中存活下来。我们发现,斑块中的细菌既可以通过突变(即产生抗性)逃避噬菌体的攻击,也可以不通过突变(即产生持久性)逃避噬菌体的攻击。具体来说,虽然从有明显基因突变(如导致粘液性)的斑块中分离出了抗 T4 和抗 lambda 的细菌,但它们的敏感性比 T4 低 10 万倍以上,而且在 T2 感染后也发现了一些细胞,它们没有发生明显突变,保持了野生型噬菌体的敏感性,并能在致命剂量的抗生素中存活下来。与此相印证的是,与添加到指数生长细胞中的噬菌体相比,添加到持久细胞中的 T2 噬菌体的存活率要高出 137,000 倍。此外,我们的研究结果似乎具有普遍性,因为噬菌体处理肺炎克雷伯氏菌和铜绿假单胞菌也会产生持久细胞。因此,除了耐药菌株,细菌在噬菌体感染过程中也会形成持久细胞。
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引用次数: 0
The role of Streptomyces to achieve the United Nations sustainable development goals. Burning questions in searching for new compounds 链霉菌在实现联合国可持续发展目标中的作用。寻找新化合物的迫切问题。
IF 5.7 2区 生物学 Pub Date : 2024-08-03 DOI: 10.1111/1751-7915.14541
Miriam Rodríguez, Lorena Cuervo, Laura Prado-Alonso, María Soledad González-Moreno, Carlos Olano, Carmen Méndez

In the 21st century, the world is facing persistent global problems that have led to 193 countries to agree on the 17 Sustainable Development Goals (SDGs). The United Nations introduced these goals in 2015 to find solutions that could help end poverty, promote prosperity and protect the planet (United Nations, 2016a). In this brief perspective, we will discuss the potential role of Streptomyces in achieving those SDGs, focusing it in the current strategies applied for discovering novel compounds and in some of the problems that must be faced (Figure 1).

Members of the genus Streptomyces are filamentous Gram-positive bacteria belonging to the phylum Actinobacteria. They are ubiquitous microorganisms mainly found in soil but they can also inhabit other niches like seawater or deserts, or living associated with other organisms (Sivalingam et al., 2019). Streptomyces is mainly known for its ability to produce a wide array of bioactive secondary metabolites, which have several interesting applications in different fields (Alam et al., 2022; Demain & Sanchez, 2009; Donald et al., 2022).

One of the problems that most concern the United Nations is the existence of a growing demand for food in today's world (Food security information network, 2023). In this context, Streptomyces could play a relevant role in achieving SDG 2 (zero hunger, improved nutrition and sustainable agriculture) and SDG 1 (end poverty). Streptomyces produces several metabolites with significant commercial relevance in enhancing the nutritional value of human food and animal feed, such as vitamins like cobalamin (Rex et al., 2022). Additionally, there is an increasing need for enzymes in the global market (Grand View Research, 2023). Streptomyces due to its wide metabolic potential is used for the sustainable biotechnological production of a broad assortment of enzymes such as proteases, xylanases, amylases, lipases, keratinases, cellulases, dextranases and chitinases among others (Fernandes de Souza et al., 2022; Kumar et al., 2020). These enzymes have applications in several fields, and advantages not only in terms of energy consumption, stability, substrate specificity, purity or reaction efficiency but also in ecological and waste generation, thus contributing to the achievement of sustainable industrialization and innovation (SDG 9) and promoting responsible production and consumption (SDG 12). An example of enzymes with ecological applications is the degradation of lignocellulose and dye decolourization by detergent-stable peroxidases and laccases (Cuebas-Irizarry & Grunden, 2024). These enzymes can be potentially used to treat wastewater resulting from human activities like textile and paper industries, which cause environmental pollution and wastes that affect life below

然而,尽管在文献中可以找到一些成功的例子,但通过基因组挖掘发现的smBGC的巨大多样性只能部分地转化为发现新的生物活性NPs,而鉴定和表征这些预测的smBGC编码的化合物仍然需要大量的实验室工作。因此,smBGC 可以表达或低表达,但在标准实验室条件下无法检测到预测编码的化合物(隐性产物),或者识别出的 smBGC 没有表达,其产物也无法观察到(具有隐性产物的沉默 BGC)。所有这些情况都是 "已知未知 "次级代谢物的典型例子(Hoskisson &amp; Seipke, 2020)。因此,利用基因组挖掘方法取得成功的一个关键问题是找到开启或增加这些沉默或低表达的 smBGCs 表达的策略。为此,人们采用了多种遗传策略,如过度表达正调控因子;失活负调控因子;异源表达 smBGC;或在 BGC 操作子上游插入强启动子(Olano, García, et al.)其他缓解鉴定隐性产物挑战的策略有:OSMAC(一株多种化合物)(Pan 等人,2019 年);模拟生产者的生态环境(Cuervo 等人,2022 年);将前体重定向到目标生物合成途径(Kallifidas 等人,2018 年);全局调控因子工程(Cuervo 等人,2023 年);或核糖体工程(Zhu 等人,2019 年)。然而,我们必须牢记,在整个历史长河中,药物发现的主要瓶颈之一就是不断重新发现已知化合物。从这个角度来看,一些智能生物信息学基因组挖掘方法可以增加识别未知 smBGCs 的机会,这些 smBGCs 编码的新化合物具有潜在的临床应用价值。例如,近年来已经使用了几种策略,如挖掘抗性基因(Culp 等人,2020 年)或链霉菌抗生素调节蛋白基因(Ye 等人,2023 年)。此外,搜索参与不寻常功能基团生物合成的基因也被用作选择新的 smBGCs 的一种方法,如瞄准卤化酶基因(Prado-Alonso 等人,2022 年);多酮苷合成酶中编码硫结合特异性二聚体 DUF-SH 的 DNA 区域(Pan 等人,2017 年);C-末端硫代硫酸钠基因(C-末端硫代硫酸钠基因,2022 年);多酮苷合成酶中编码硫结合特异性二聚体 DUF-SH 的 DNA 区域(Pan 等人,2017 年)、基因组挖掘的另一个重要应用是作为基因组和装置的储备库,用于组合生物合成策略。这种方法最大限度地利用了合成生物学技术,通过使用不同的基因工程策略生成具有新型基因组合的 smBGCs。这些基因将编码新的生物合成途径,有可能指导具有不同或改进特性的新天然产品的生物合成。组合生物合成包括几种策略,如将本地生物合成基因与来自其他 smBGCs 的基因相结合、将来自其他 smBGCs 的基因表达到特定生物合成步骤受阻的突变体中、基于使用不同生物合成前体的突变合成,或将上述所有策略结合起来以获得新的结构单元(Olano 等人,2009 年)。这种方法已成功用于多种化合物新衍生物的生物合成,如萜类化合物(Tang 等人,2022 年)、非核糖体肽(Ruijne &amp; Kuipers,2021 年)、RiPPs(核糖体合成和翻译后修饰的肽)(Sardar &amp; Schmidt,2016 年)、多酮类化合物(Wang 等人,2022 年)或核苷类化合物(Niu 等人,2017 年)。一个有趣的例子是从米曲霉素(Núñez 等人,2012 年)衍生出的新型糖基化类似物 demycarosyl-3D-β-D-digitoxosylmithramycin SK(图 2)。这种化合物的生产是通过为一种在米曲霉素 BGC 的酮还原酶基因上发生突变的 S. argillaceus 菌株提供合成 D-二乙氧基糖的能力而实现的。与亲代化合物相比,这种类似物显示出较高的抗肿瘤活性和较低的毒性,此外,它还能抑制 EWS-FLI1 的活性,这表明它具有临床开发的潜力(Osgood 等人,2016 年)。另一个例子是生产表柔比星(图 2),这是一种心脏毒性较低的多柔比星衍生物,最初是通过半合成法生产的。我们设计了一种新的生产方法,将阿维菌素和红霉素基因簇中的 avrE 或 eryBIV 表达到 S. peucetius 多柔比星非生产突变体中(Demain &amp; Vaishnav, 2011)。
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引用次数: 0
期刊
Microbial Biotechnology
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