Synthetic Turing protocells: vesicle self-reproduction through symmetry-breaking instabilities

The reproduction of a living cell requires a repeatable set of chemical events to be properly coordinated. Such events define a replication cycle, coupling the growth and shape change of the cell membrane with internal metabolic reactions. Although the logic of such process is determined by potentially simple physico-chemical laws, modelling of a full, self-maintained cell cycle is not trivial. Here we present a novel approach to the problem that makes use of so-called symmetry breaking instabilities as the engine of cell growth and division. It is shown that the process occurs as a consequence of the breaking of spatial symmetry and provides a reliable mechanism of vesicle growth and reproduction. Our model opens the possibility of a synthetic protocell lacking information but displaying self-reproduction under a very simple set of chemical reactions.     

合成生物学

近年来用化学合成的手段合成生物物质的研究进展很快。有感染活力的小儿麻痹症病毒RNA与φX-174噬菌体基因先后合成成功。估计2006年可能会有能合成1百万bp DNA的仪器问世。此外,目前已能向蛋白质中引入80种非常见氨基酸,从而使蛋白质获得新的性质。化学合成的进展使合成与改造生命成为现实,这对研究生物学基本规律有很大的意义,但这也是一把“双刃剑”,带来伦理与反恐的问题及对可能的潜在威胁的担忧。2004年6月在美国麻省理工学院举行了第一届合成生物学国际会议。2005年8月在美国旧金山举行的合成生物学会议,讨论了生物合成这个领域对药物发展、细胞重编程、生物机器人等方面的潜在意义。     

Synthetic biology in plastids

Plastids (chloroplasts) harbor a small gene‐dense genome that is amenable to genetic manipulation by transformation. During 1 billion years of evolution from the cyanobacterial endosymbiont to present‐day chloroplasts, the plastid genome has undergone a dramatic size reduction, mainly as a result of gene losses and the large‐scale transfer of genes to the nuclear genome. Thus the plastid genome can be regarded as a naturally evolved miniature genome, the gradual size reduction and compaction of which has provided a blueprint for the design of minimum genomes. Furthermore, because of the largely prokaryotic genome structure and gene expression machinery, the high transgene expression levels attainable in transgenic chloroplasts and the very low production costs in plant systems, the chloroplast lends itself to synthetic biology applications that are directed towards the efficient synthesis of green chemicals, biopharmaceuticals and other metabolites of commercial interest. This review describes recent progress with the engineering of plastid genomes with large constructs of foreign or synthetic DNA, and highlights the potential of the chloroplast as a model system in bottom‐up and top‐down synthetic biology approaches.     

合成生物学在微生物细胞工厂构建中的应用

通过微生物发酵的方法生产大宗化学品和天然产物能够部分替代石油化工炼制和植物提取。合成生物学技术的发展极大地提高了构建微生物细胞工厂生产大宗化学品和天然产物的能力。一方面综述了合成生物学在构建细胞工厂时的关键技术,包括最优合成途径的设计、合成途径的创建与优化、细胞性能的优化;另一方面,介绍了应用这些技术构建细胞工厂生产燃料化学品、大宗化学品和天然产物的典型案例。     

Synthetic biology in biofilms: Tools,challenges, and opportunities

The field of synthetic biology seeks to program living cells to perform novel functions with applications ranging from environmental biosensing to smart cell-based therapeutics. Bacteria are an especially attractive chassis organism due to their rapid growth, ease of genetic manipulation, and ability to persist across many environmental niches. Despite significant progress in bacterial synthetic biology, programming bacteria to perform novel functions outside the well-controlled laboratory context remains challenging. In contrast to planktonic laboratory growth, bacteria in nature predominately reside in the context of densely packed communities known as biofilms. While biofilms have historically been considered environmental and biomedical hazards, their physiology and emergent behaviors could be leveraged for synthetic biology to engineer more capable and robust bacteria. Specifically, bacteria within biofilms participate in complex emergent behaviors such as collective organization, cell-to-cell signaling, and division of labor. Understanding and utilizing these properties can enable the effective deployment of engineered bacteria into natural target environments. Toward this goal, this review summarizes the current state of synthetic biology in biofilms by highlighting new molecular tools and remaining biological challenges. Looking to future opportunities, advancing synthetic biology in biofilms will enable the next generation of smart cell-based technologies for use in medicine, biomanufacturing, and environmental remediation.     

植物来源药用天然产物的合成生物学研究进展

大多数药用天然产物在植物中含量低微,提取分离困难;而且这些化合物一般结构复杂,化学合成难度大,还容易造成环境污染.基于合成生物学技术获得药用天然产物具有绿色环保和可持续发展等优点.文中以药用萜类化合物人参皂苷、紫杉醇、青蒿素、丹参酮,生物碱类化合物长春新碱、吗啡以及黄酮类化合物灯盏花素为例,总结了植物来源药用萜类、生物...     

合成生物学与天然产物开发

天然产物依然是临床用药的重要来源。合成生物学的诞生为天然产物的开发提供了全新的机遇,传统的微生物药物、植物天然产物等研究领域都因合成生物学而获得新生。重点介绍了合成生物学在天然产物开发中的应用,包括新化合物及其生物合成元件的筛选,基于理性设计的天然产物异源生物合成,人工底盘细胞的系统优化等。     

Synthetic biology in multicellular organisms: Opportunities in nematodes

Synthetic biology has mainly focused on introducing new or altered functionality in single cell systems: primarily bacteria, yeast, or mammalian cells. Here, we describe the extension of synthetic biology to nematodes, in particular the well-studied model organism Caenorhabditis elegans, as a convenient platform for developing applications in a multicellular setting. We review transgenesis techniques for nematodes, as well as the application of synthetic biology principles to construct nematode gene switches and genetic devices to control motility. Finally, we discuss potential applications of engineered nematodes.     

Synthetic biology: building the language for a new science brick by metaphorical brick

Changes in the biosciences and their relations to society over the last decades provide a unique opportunity to examine whether or not such changes leave traces in the language we use to talk about them. In this article we examine metaphors used in English-speaking press coverage to conceptualize a new type of (interdisciplinary) bioscience: synthetic biology. Findings show that three central metaphors were used between 2008 and May 2010. They exploit social and cultural knowledge about books, computers and engines and are linked to knowledge of three revolutions in science and society (the printing, information and industrial revolutions). These three central metaphors are connected to each other through the concepts of reading/writing, designing and mass production and they focus on science as a revolutionary process rather than on the end results or products of science. Overall, we observed the use of a complex bricolage of mixed metaphors and chains of metaphors that root synthetic biology in historical events and achievements, while at the same time extolling its promises for the future.     

Synthetic biology approach to reconstituting the ubiquitylation cascade in bacteria

Covalent modification of proteins with ubiquitin (Ub) is widely implicated in the control of protein function and fate. Over 100 deubiquitylating enzymes rapidly reverse this modification, posing challenges to the biochemical and biophysical characterization of ubiquitylated proteins. We circumvented this limitation with a synthetic biology approach of reconstructing the entire eukaryotic Ub cascade in bacteria. Co‐expression of affinity‐tagged substrates and Ub with E1, E2 and E3 enzymes allows efficient purification of ubiquitylated proteins in milligram quantity. Contrary to in‐vitro assays that lead to spurious modification of several lysine residues of Rpn10 (regulatory proteasomal non‐ATPase subunit), the reconstituted system faithfully recapitulates its monoubiquitylation on lysine 84 that is observed in vivo. Mass spectrometry revealed the ubiquitylation sites on the Mind bomb E3 ligase and the Ub receptors Rpn10 and Vps9. Förster resonance energy transfer (FRET) analyses of ubiquitylated Vps9 purified from bacteria revealed that although ubiquitylation occurs on the Vps9‐GEF domain, it does not affect the guanine nucleotide exchanging factor (GEF) activity in vitro. Finally, we demonstrated that ubiquitylated Vps9 assumes a closed structure, which blocks additional Ub binding. Characterization of several ubiquitylated proteins demonstrated the integrity, specificity and fidelity of the system, and revealed new biological findings.     

合成生物学的医学应用

合成生物学旨在基于工程学原理,通过人工合成生物调控元件、模块和基因调控网络等对细胞进行设计和改造,以实现细胞和生命体的定向演化。在医学研究中,合成生物学主要采用人工设计合成治疗性的基因回路,制备工程化细胞植入体内,纠正机体已发生缺陷的生物调控元件,以达到治疗疾病的目的。本文对合成生物学的兴起、发展及其在医学中的应用和研究进展进行了综述。     

Cell biology

A selection of World Wide Web sites relevant to papers published in this issue of Current Opinion in Plant Biology.     

天然产物类药物的合成生物学研究

结构复杂多样的天然产物是现代药物的重要组成部分和新药发现的重要源泉。建立在基因工程及代谢工程、合成化学、基因组学、系统生物学等学科基础上的合成生物学研究对于结构复杂的天然产物类药物研究有特殊的意义。核心是通过在发酵友好、高效的微生物中设计、构建目标化合物的生物合成途径,经系统地调控和优化由重组微生物发酵生产来源稀缺的天然产物类药物或前体。该方法是不远的将来解决来源、成本与环境、资源协调问题最好的途径之一,也是解决海洋天然产物或特殊生境微生物药物面临的如何持续供应化合物这一个瓶颈问题的最佳选择。该文将对天然产物类药物合成生物学研究涉及的主要策略和重要进展进行阐述。     

Whither systems biology

Cell biologists are interested in how complexity arises from the interaction of different molecules. However, cells are many orders of magnitude larger than the protein-binding interfaces. To bridge these vast difference in scales, biologists construct hierarchies of organization of cellular structures. I describe how systems biology provides an approach to bridge these different scales.     

芳香类天然产物的合成生物学研究进展

植物芳香类天然产物具有重要的药用价值,可制成具有抗菌、抗炎、镇痛、抗氧化、杀虫驱虫、祛痰止咳、安神镇静和抗肿瘤等药效的医药保健用品.然而,由于植物中芳香类天然产物含量较低并且难以提取和纯化,严重限制了其工业化生产及应用.合成生物学和代谢工程技术的发展为天然产物的生产提供了新的思路,可以利用人工微生物细胞工厂来实现多种芳...     

Synthetic biology for bioengineering virus-like particle vaccines

Vaccination is the most effective method of disease prevention and control. Many viruses and bacteria that once caused catastrophic pandemics (e.g., smallpox, poliomyelitis, measles, and diphtheria) are either eradicated or effectively controlled through routine vaccination programs. Nonetheless, vaccine manufacturing remains incredibly challenging. Viruses exhibiting high antigenic diversity and high mutation rates cannot be fairly contested using traditional vaccine production methods and complexities surrounding the manufacturing processes, which impose significant limitations. Virus-like particles (VLPs) are recombinantly produced viral structures that exhibit immunoprotective traits of native viruses but are noninfectious. Several VLPs that compositionally match a given natural virus have been developed and licensed as vaccines. Expansively, a plethora of studies now confirms that VLPs can be designed to safely present heterologous antigens from a variety of pathogens unrelated to the chosen carrier VLPs. Owing to this design versatility, VLPs offer technological opportunities to modernize vaccine supply and disease response through rational bioengineering. These opportunities are greatly enhanced with the application of synthetic biology, the redesign and construction of novel biological entities. This review outlines how synthetic biology is currently applied to engineer VLP functions and manufacturing process. Current and developing technologies for the identification of novel target-specific antigens and their usefulness for rational engineering of VLP functions (e.g., presentation of structurally diverse antigens, enhanced antigen immunogenicity, and improved vaccine stability) are described. When applied to manufacturing processes, synthetic biology approaches can also overcome specific challenges in VLP vaccine production. Finally, we address several challenges and benefits associated with the translation of VLP vaccine development into the industry.     

合成生物学与代谢工程

随着DNA重组技术的日趋成熟,代谢工程的理论和应用已经得到了迅速发展。合成生物学是近年来蓬勃发展的一门新兴学科,在许多领域都具有重要的应用。以下从改造细胞代谢的关键因子、代谢途径的调节和宿主细胞与代谢途径构建的关系等方面详细讨论了合成生物学的最新进展和合成生物学在代谢工程领域的应用。     

合成生物学与微生物遗传物质的重构

作为一门新兴学科的合成生物学已经展现出巨大的科学价值和应用前景。近年来已经发表了多篇综述文章,从不同角度对合成生物学进行了总结和论述。文章首次对合成生物学和微生物遗传学之间的关系进行了阐述,同时介绍了合成生物学在微生物遗传物质的重构方面最近的研究进展,包括微生物遗传物质的合成、设计和精简,遗传元件的标准化和遗传线路的模块化。也探讨了合成生物学与微生物遗传工程的关系。