Engineering Bacterial Cellulose by Synthetic Biology

Synthetic biology is an advanced form of genetic manipulation that applies the principles of modularity and engineering design to reprogram cells by changing their DNA. Over the last decade, synthetic biology has begun to be applied to bacteria that naturally produce biomaterials, in order to boost material production, change material properties and to add new functionalities to the resulting material. Recent work has used synthetic biology to engineer several Komagataeibacter strains; bacteria that naturally secrete large amounts of the versatile and promising material bacterial cellulose (BC). In this review, we summarize how genetic engineering, metabolic engineering and now synthetic biology have been used in Komagataeibacter strains to alter BC, improve its production and begin to add new functionalities into this easy-to-grow material. As well as describing the milestone advances, we also look forward to what will come next from engineering bacterial cellulose by synthetic biology.     

达托霉素及其衍生物生物合成的研究进展

随着高致病耐药菌的不断出现,临床上对新抗生素的需求十分迫切。达托霉素作为环脂肽类抗生素的第一个产品对耐药菌有很好的杀菌效果,且制剂用药方便,毒副作用小,被公认为病原菌最后一道防线--万古霉素的最佳替代品。本文在介绍达托霉素的理化特征和抗菌活性、合成基因簇的研究成果的基础上,重点对达托霉素及其衍生物的研究状况进行了综述,对达托霉素的生产及其衍生物的开发进行了展望：结合系统生物学为已有的达托霉素产生菌进一步进行代谢工程改造提供指导;通过合成生物学使达托霉素衍生物成为新型抗生素。     

Synthetic Biology Approaches in the Development of Engineered Therapeutic Microbes

Since the intimate relationship between microbes and human health has been uncovered, microbes have been in the spotlight as therapeutic targets for several diseases. Microbes contribute to a wide range of diseases, such as gastrointestinal disorders, diabetes and cancer. However, as host-microbiome interactions have not been fully elucidated, treatments such as probiotic administration and fecal transplantations that are used to modulate the microbial community often cause nonspecific results with serious safety concerns. As an alternative, synthetic biology can be used to rewire microbial networks such that the microbes can function as therapeutic agents. Genetic sensors can be transformed to detect biomarkers associated with disease occurrence and progression. Moreover, microbes can be reprogrammed to produce various therapeutic molecules from the host and bacterial proteins, such as cytokines, enzymes and signaling molecules, in response to a disturbed physiological state of the host. These therapeutic treatment systems are composed of several genetic parts, either identified in bacterial endogenous regulation systems or developed through synthetic design. Such genetic components are connected to form complex genetic logic circuits for sophisticated therapy. In this review, we discussed the synthetic biology strategies that can be used to construct engineered therapeutic microbes for improved microbiome-based treatment.     

Chemical Biology: Here to Stay?

The term chemical biology emerged about 25 years ago and encompasses a set of research inquiries at the intersections of chemistry and biology. Before chemical biology there was biological chemistry for 100 years or more, but the traverse from one to the other has not just been a switching of noun and adjective. Over the past quarter century chemists, many from organic synthetic lineages, have become convinced that the open systems of biology have become appropriate venues to bring chemical thinking for library design, screening, and molecular scaffold optimization. Whereas biological chemistry may be described as the universe of chemistry that happens in nature, chemical biologists often bring new, unnatural molecular scaffolds to decipher the logics of biology. That seems a limiting definition and I prefer the mantra: think chemically, act biologically.     

G‐Quadruplexes as Tools for Synthetic Biology

With the potential to engineer biological systems, synthetic biology is an emerging field that combines various disciplines of sciences. It encompasses combinations of DNA, RNA and protein modules for constructing desired systems and the “rewiring” of existing signalling networks. Despite recent advances, this field still lags behind in the artificial reconstruction of cellular processes, and thus demands new modules and switches to create “genetic circuits”. The widely characterised noncanonical nucleic acid secondary structures, G‐quadruplexes are promising candidates to be used as biological modules in synthetic biology. Structural plasticity and functional versatility are significant G‐quadruplex traits for its integration into a biological system and for diverse applications in synthetic circuits.     

Chemical Biology Tools To Investigate Malaria Parasites

Parasitic diseases like malaria tropica have been shaping human evolution and history since the beginning of mankind. After infection, the response of the human host ranges from asymptomatic to severe and may culminate in death. Therefore, proper examination of the parasite's biology is pivotal to deciphering unique molecular, biochemical and cell biological processes, which in turn ensure the identification of treatment strategies, such as potent drug targets and vaccine candidates. However, implementing molecular biology methods for genetic manipulation proves to be difficult for many parasite model organisms. The development of fast and straightforward applicable alternatives, for instance small-molecule probes from the field of chemical biology, is essential. In this review, we will recapitulate the highlights of previous molecular and chemical biology approaches that have already created insight and understanding of the malaria parasite Plasmodium falciparum. We discuss current developments from the field of chemical biology and explore how their application could advance research into this parasite in the future. We anticipate that the described approaches will help to close knowledge gaps in the biology of P. falciparum and we hope that researchers will be inspired to use these methods to gain knowledge – with the aim of ending this devastating disease.     

Food synthetic biology-driven protein supply transition: From animal-derived production to microbial fermentation

Animal-derived protein production is one of the major traditional protein supply methods, which continues to face increasing challenges to satisfy global needs due to population growth, augmented individual protein consumption, and aggravated environmental pollution. Thus, ensuring a sustainable protein source is a considerable challenge. The emergence and development of food synthetic biology has enabled the establishment of cell factories that effectively synthesize proteins, which is an important way to solve the protein supply problem. This review aims to discuss the existing problems of traditional protein supply and to elucidate the feasibility of synthetic biology in the process of protein synthesis. Moreover, using artificial bioengineered milk and artificial bioengineered eggs as examples, the progress of food protein supply transition based on synthetic biology has been systematically summarized. Additionally, the future of food synthetic biology as a potential source of protein has been also discussed. By strengthening and innovating the application of food synthetic biology technologies, including genetic engineering and high-throughput screening methods, the current limitations of artificial foods for protein synthesis and production should be addressed. Therefore, the development and industrial production of new food resources should be explored to ensure safe, high-quality, and sustainable global protein supply.     

Visualizing and Manipulating Biological Processes by Using HaloTag and SNAP-Tag Technologies

Visualizing and manipulating the behavior of proteins is crucial to understanding the physiology of the cell. Methods of biorthogonal protein labeling are important tools to attain this goal. In this review, we discuss advances in probe technology specific for self-labeling protein tags, focusing mainly on the application of HaloTag and SNAP-tag systems. We describe the latest developments in small-molecule probes that enable fluorogenic (no wash) imaging and super-resolution fluorescence microscopy. In addition, we cover several methodologies that enable the perturbation or manipulation of protein behavior and function towards the control of biological pathways. Thus, current technical advances in the HaloTag and SNAP-tag systems means that they are becoming powerful tools to enable the visualization and manipulation of biological processes, providing invaluable scientific insights that are difficult to obtain by traditional methodologies. As the multiplex of self-labeling protein tag systems continues to be developed and expanded, the utility of these protein tags will allow researchers to address previously inaccessible questions at the forefront of biology.     

分子生物学主要网络资源及教学应用

对互联网上分子生物学资源的熟练应用可保证教学研究内容的创造性、高效性和科学性,文章较系统的介绍了分子生物学的主要网络资源,其类型包括数据库、软件、网络教学、虚拟实验、综合性网站及论坛等。这些介绍有利于分子生物学网络资源的广泛传播及应用,将进一步促进科研、教学及其他相关领域的发展。     

合成生物学研究进展

合成生物学是以工程化设计思路,构建标准化的元器件和模块,改造已存在的天然系统或者从头合成全新的人工生命体系,实现在化学品合成(包括材料、能源和天然化合物)、医学、农业、环境等领域的应用。人们利用基本的生物学元件设计和构建了基因开关、振荡器、放大器、逻辑门、计数器等合成器件,实现对生命系统的重新编程并执行特殊功能。模块化处理生物的代谢途径,并在底盘细胞上进行组装和优化,可以实现大宗化学品和精细化学品的合成。目前人们已经在丁醇、异丁醇、青蒿素和紫杉醇等化合物的生物合成上取得了重要进展。近年来还发展了多种基因组编辑和组装技术,可精确地对基因组进行编辑,人们还成功地合成了噬菌体基因组、支原体基因组和酵母基因组。在未来的50～100年内,合成生物学将对人类的医疗、化学品制造(含药品)、军事产生渐进性的、渗透性的但颠覆性的意义。     

In Vivo Expression of Genetic Information from Phosphoramidate–DNA

Chemically modified genes and genomes with customized properties will become a valuable tool in numerous fields, including synthetic biology, biotechnology, and medicine. These genetic materials are meant to store and exchange information with DNA and RNA while tuning their functionality. Herein, we outline the development of an alternative genetic system carrying phosphoramidate linkages that successfully propagates genetic information in bacteria and at the same time is labile to acidic conditions. The P3′→N5′ phosphoramidate-containing DNA (PN-DNA) was enzymatically synthesized by using 5′-amino-2′,5′-deoxycytidine 5′-N-triphosphates (NH-dCTPs) as substrates for DNA polymerases and employed to encode antibiotic resistance in Escherichia coli. The resulting PN-DNA can be efficiently destroyed by mild acidic conditions, whereas an unmodified counterpart remains intact. A cloning strategy was proposed for assembling modified fragments into a genome. This method can be of interest to scientists working in the field of orthogonal nucleic acid genes and genomes.     

How To Quantify a Genetic Firewall? A Polarity-Based Metric for Genetic Code Engineering

Genetic code engineering aims to produce organisms that translate genetic information in a different way from that prescribed by the standard genetic code. This endeavor could eventually lead to genetic isolation, where an organism that operates under a different genetic code will not be able to transfer functional genes with other living species, thereby standing behind a genetic firewall. It is not clear however, how distinct the code should be, or how to measure the distance. We have developed a metric (Δ_code) where we assigned polarity indices (clog D₇) to amino acids to calculate the distances between pairs of genetic codes. We then calculated the distance between a set of 204 genetic codes, including the 24 known distinct natural codes, 11 extreme-distance codes created computationally, nine theoretical special purpose codes from literature and 160 codes in which canonical amino acids were replaced by noncanonical chemical analogues. The metric can be used for building strategies towards creating semantically alienated organisms, and testing the strength of genetic firewalls. This metric provides the basis for a map of the genetic codes that could guide future efforts towards novel biochemical worlds, biosafety and deep barcoding applications.     

Construction of microbial cell factories for industrial bioprocesses

The development of industrial microbial processes is gaining unprecedented momentum. Increased concern for environmental issues and the prospect of declining petroleum resources has shifted the industrial focus increasingly to microorganisms as biocatalysts. At the same time systems biology and synthetic biology supply industry and academia with new tools to design optimal microbial cell factories. Among the tools are systems biology approaches allowing the modelling of cellular networks for rational strain design, single cell analyses methods for gaining insight into population hetereogeneity, and an exciting combination of tools from structural biology and synthetic biology, permitting the catalysis of new (unnatural) enzymatic reactions or the production of new (unnatural) chemicals. This perspective article outlines recent advances and new developments within the field of microbial cell factory design. Copyright © 2012 Society of Chemical Industry     

The Chemical Biology-Medicinal Chemistry Continuum: EFMC′s Vision

The E uropean F ederation for M edicinal chemistry and C hemical biology (EFMC) is a federation of learned societies. It groups organizations of European scientists working in a dynamic field spanning chemical biology and medicinal chemistry. New ideas, tools, and technologies emerging from a wide array of scientific disciplines continuously energize this rapidly evolving area. Medicinal chemistry is the design, synthesis, and optimization of biologically active molecules aimed at discovering new drug candidates – a mission that in many ways overlaps with the scope of chemical biology. Chemical biology is by now a mature field of science for which a more precise definition of what it encompasses, in the frame of EFMC, is timely. This article discusses chemical biology as currently understood by EFMC, including all activities dealing with the design and synthesis of biologically active chemical tools and their use to probe, characterize, or influence biological systems.     

论杀虫剂穿透生物学与昆虫抗药性测定

阐明了杀虫剂穿透生物学的基本概念及其对昆虫抗药性测定的指导意义;论述了杀虫剂穿透生物学提出的背景及其与“田间毒理学”的关系,分析了在昆虫抗药性生物测定中存在的问题及其主要原因;提出了杀虫剂穿透生学在昆虫抗药性测定中的应用原则。     

生物絮凝剂法在废水处理中的应用研究

混凝法是废水处理中最常用的重要方法,而絮凝剂的性质、种类的好坏是关系到混凝处理效果的关键因素。本文首先对生物絮凝剂的絮凝机理,影响生物絮凝剂絮凝能力的因素以及可被生物絮凝剂絮凝的物质进行了介绍;然后对其在废水处理中的应用作为重要叙述;最后对生物絮凝剂的发展前景作了简要概括。     

化学生物学的科学内涵及其发展

化学生物学是化学和生物学的交叉科学 ,是利用化学的理论、研究方法和手段来探索生物医学问题的科学。化学生物学正迅速成为一个重要的交叉学科领域 ,因此 ,对每个化学研究者来说 ,了解和掌握化学生物学是非常重要的     

基于系统生物学和合成生物学的重要平台化学品生物制造的研究进展

基于生物质资源的平台化学品制造,是解决目前石化资源枯竭和环境问题的重要措施,对经济社会的可持续发展具有重要意义。本文主要介绍了系统生物学和合成生物学在有机酸(琥珀酸、富马酸、L-苹果酸、葡萄糖二酸、丙酮酸、苯丙酮酸、α-酮戊二酸)以及其他平台化学品(2,5-呋喃二甲酸)生物制造中的应用,并展望了生物制造在平台化学品生产中的未来发展方向。     

细胞生物学实验教学的改革与创新

细胞生物学是21世纪发展最为迅速的前沿学科之一,同时也是生命科学领域的基础学科。细胞生物学实验教学在提高学生的实践动手能力,培养学生的实践创新能力中发挥着不可替代的作用。因此,细胞生物学实验教学的改革与创新是十分必要的。本文分析了细胞生物学实验教学的现状,并对其实验教学的改革措施进行了探讨。