微生物酶工程：绿色生物制造的基石

酶工程是酶学与工程科学融合的综合性科学技术,新酶的发掘、对酶的结构与功能的认知及酶的改造是合成生物学、生物制造技术的重要科学与技术基础。在合成生物学的发展方兴未艾的今天,酶工程更是不可或缺的研究领域。     

基于合成生物学的微生物制造研究进展

基于合成生物学的微生物制造在天然产物药物、生物能源、生物基化学品及生物传感器件的研究中发挥越来越重要的作用。本文系统地介绍了合成生物学研究领域的最新技术进展,包括DNA和染色体合成、新生物元件开发与元件库标准化、染色体工程与最小基因组技术、途径装配技术等,并阐述了合成生物学在微生物制造领域内所取得的突破和巨大的应用价值。     

合成生物学技术在环境保护中的应用

合成生物学是一个基于生物学和工程学原理的科学领域，其目的是重新设计和重组微生物，以优化或创建具有增强功能的新生物系统。该领域利用分子工具、系统生物学和遗传框架的重编程，从而构建合成途径以获得具有替代功能的微生物。传统上，合成生物学方法通常旨在开发具有成本效益的微生物细胞工厂进而从可再生资源中生产化学物质。然而，近年来合成生物学技术开始在环境保护中发挥着更直接的作用。本综述介绍了基因工程中的合成生物学工具，讨论了基于基因工程的微生物修复策略，强调了合成生物学技术可以通过响应特定污染物进行生物修复来保护环境。其中，规律间隔成簇短回文重复序列（Clustered Regularly Interspersed Short Palindromic Repeats，CRISPR）技术在基因工程细菌和古细菌的生物修复中得到了广泛应用，生物修复领域也出现了很多新的先进技术，包括生物膜工程、人工微生物群落的构建、基因驱动、酶和蛋白质工程等。有了这些新的技术和工具，生物修复将成为当今最好和最有效的污染物去除方式之一。     

合成生物学：从“造物致用”到产业转化

“合成生物学”在生命科学研究中汇聚了工程、物理、化学、数学、计算机等学科的进展,采用工程科学的研究理念,对生物体进行有目标地设计、改造乃至重新合成,甚至创建赋予非自然功能的“人造生命”,推动了从认识生命到设计生命的跨越,正在引领产业技术变革和生物经济可持续发展。本文结合中国科学院天津工业生物技术研究所作为我国合成生物学领域重要代表成立十年来的发展,聚焦“造物致用”,简要回顾和梳理了国内外合成生物学的重要科技进展与产业发展状况,并展望分析了我国合成生物学的未来发展。     

合成微生物学研究的若干前沿的思考

1 引言 合成生物学是建筑在工程学和生物学基础上、正在迅速发展、以创新为导向的崭新研究领域.高通量低成本的基因测序技术、DNA 合成技术及其公司化运作,以及各种高通量的细胞功能组分分析技术为该领域发展奠定坚实的基础.合成生物学旨在工程学思想的指导下,从头设计并构建新的生物元件、装置和系统,或对现有的、天然的生物系统进行重新设计和改造.     

利用合成生物学生产药物和燃料

合成生物学是一个快速发展的研究领域,其重要性体现在科学研究和应用开发两方面。它不但加深了我们对复杂的生物过程与机理的理解,而且使得基础生物研究向实际应用的快速转化成为可能。将介绍一些新型高效的合成生物学工具以及如何利用它们开发能从可再生原料生产药物和燃料的上程菌株。     

2017合成生物学专刊序言

近10年来,合成生物学的发展受到广泛关注。为了集中报道本领域的最新研究进展,特组织出版了此合成生物学专刊。本专刊分3个栏目:科学意义、新技术新方法和应用领域,重点介绍了合成生物学的科学内涵、技术方法进步及合成生物学在医学、药物、农业、材料、环境和能源等领域的应用前景。     

2013合成生物学专刊序言

合成生物学目前在全球得到迅猛发展。在此专刊中,综述了一些相关技术在合成生物学领域的进展,其中有:链霉菌无痕敲除方法、基因合成技术、DNA组装新方法、最小化基因组的方法及分析、合成生物系统的组合优化。也讨论了应用合成生物学策略优化光合蓝细菌底盘、产溶剂梭菌分子遗传操作技术、蛋白质预算(Protein budget)作为合成生物学的成本标尺。最后,用几个例子说明了合成生物学的应用,包括复杂天然产物合成人工生物系统的设计与构建、微生物木糖代谢途径改造制备生物基化学品以及构建酿酒酵母工程菌合成香紫苏醇。     

植物合成生物学领域发展态势的文献计量分析

合成生物学作为一种颠覆性技术可应用于农业领域的创新发展,解决当前农业学科中的瓶颈问题。利用文献计量学方法从领域发表论文的时序数量分布、主题分布等探测当前合成生物学的基本态势。基于领域的主题分布可知,其中植物合成生物学这一主题是稳定存在的且主题规模处于稳定增长趋势。聚焦植物合成生物学这一主题方向,在构建引文网络的基础上利用主路径分析方法从知识流动角度探测植物合成生物学领域重要知识节点,内容涵盖介子油苷生物合成途径,重要催化酶功能解析、转录因子的调控作用,组学方法的应用,利用微生物酵母进行生物物质合成,这些内容表征了合成生物的核心理论技术。     

合成生物学中的DNA组装技术

合成生物学旨在应用工程学的研究思路及手段去设计或改造生物系统,是一个综合了科学与工程的拥有发展潜力的新兴学科,在生物医药、农业、能源、环保等方面发挥着巨大作用。DNA组装技术是合成生物学中的关键技术,也是合成生物学快速发展的限制性技术。综述了众多DNA组装技术的发展及其在合成生物学研究中的意义和应用。     

合成生物学及其在生物技术中的应用进展

合成生物学是一门21世纪生物学的新兴学科,它着眼生物科学与工程科学的结合,把生物系统当作工程系统"从下往上"进行处理,由"单元"(unit)到"部件"(device)再到"系统"(system)来设计,修改和组装细胞构件及生物系统.合成生物学是分子和细胞生物学、进化系统学、生物化学、信息学、数学、计算机和工程等多学科交叉的产物.目前研究应用包括两个主要方面:一是通过对现有的、天然存在的生物系统进行重新设计和改造,修改已存在的生物系统,使该系统增添新的功能.二是通过设计和构建新的生物零件、组件和系统,创造自然界中尚不存在的人工生命系统.合成生物学作为一门建立在基因组方法之上的学科,主要强调对创造人工生命形态的计算生物学与实验生物学的协同整合.必须强调的是,用来构建生命系统新结构、产生新功能所使用的组件单元既可以是基因、核酸等生物组件,也可以是化学的、机械的和物理的元件.本文跟踪合成生物学研究及应用,对其在DNA水平编程、分子修饰、代谢途径、调控网络和工业生物技术等方面的进展进行综述.     

Computer-aided design of biological circuits using TinkerCell

Synthetic biology is an engineering discipline that builds on modeling practices from systems biology and wet-lab techniques from genetic engineering. As synthetic biology advances, efficient procedures will be developed that will allow a synthetic biologist to design, analyze, and build biological networks. In this idealized pipeline, computer-aided design (CAD) is a necessary component. The role of a CAD application would be to allow efficient transition from a general design to a final product. TinkerCell is a design tool for serving this purpose in synthetic biology. In TinkerCell, users build biological networks using biological parts and modules. The network can be analyzed using one of several functions provided by TinkerCell or custom programs from third-party sources. Since best practices for modeling and constructing synthetic biology networks have not yet been established, TinkerCell is designed as a flexible and extensible application that can adjust itself to changes in the field.     

Knowledge-making distinctions in synthetic biology

Synthetic biology is an increasingly high-profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA-based device construction, genome-driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge-making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems.     

Opportunities for yeast metabolic engineering: Lessons from synthetic biology

Constant progress in genetic engineering has given rise to a number of promising areas of research that facilitated the expansion of industrial biotechnology. The field of metabolic engineering, which utilizes genetic tools to manipulate microbial metabolism to enhance the production of compounds of interest, has had a particularly strong impact by providing new platforms for chemical production. Recent developments in synthetic biology promise to expand the metabolic engineering toolbox further by creating novel biological components for pathway design. The present review addresses some of the recent advances in synthetic biology and how these have the potential to affect metabolic engineering in the yeast Saccharomyces cerevisiae. While S. cerevisiae for years has been a robust industrial organism and the target of multiple metabolic engineering trials, its potential for synthetic biology has remained relatively unexplored and further research in this field could strongly contribute to industrial biotechnology. This review also addresses are general considerations for pathway design, ranging from individual components to regulatory systems, overall pathway considerations and whole-organism engineering, with an emphasis on potential contributions of synthetic biology to these areas. Some examples of applications for yeast synthetic biology and metabolic engineering are also discussed.     

生物元件的挖掘、改造与标准化

生物元件是合成生物学中的三大基本要素之一,是合成生物学的基石。现阶段,生物元件的挖掘、鉴定和改造仍然是合成生物学领域的重要研究方向之一。合成生物学与基因工程和代谢工程最显著的差别在于能够将大量的生物元件进行快速、随意的组装,而实现这一目标的前提是将生物元件标准化。目前,已经有大量基因组被解析,通过这些基因组数据库的注释与功能验证,并借助于各种生物信息学软件预测启动子、终止子、操纵了、转录因子和转录因子结合位点、核糖体结合位点以及蛋白质编码区等部件,为合成生物学提供丰富的生物元件信息资源。随着元基因组技术的兴起,大量未培养微生物中的基因和基因簇信息被解析,使得我们可以从占自然界中实际存在微生物总数99％的未知微生物中挖掘更多的生物元件。另外,生物元件可以从自然界分离出来,也可以对天然生物元件进行修饰、重组和改造后得到新的元件。酵母是异源蛋白表达的通用宿主和生物基产品生产的细胞工厂,但其本身可用的启动子非常有限,近年来各国学者在酵母启动子改造和文库构建方面做了很多工作,该文也将概述酵母启动子改造和在合成生物生物学研究领域中的应用方面的研究进展。     

Basic science through engineering? Synthetic modeling and the idea of biology-inspired engineering

Synthetic biology is often understood in terms of the pursuit for well-characterized biological parts to create synthetic wholes. Accordingly, it has typically been conceived of as an engineering dominated and application oriented field. We argue that the relationship of synthetic biology to engineering is far more nuanced than that and involves a sophisticated epistemic dimension, as shown by the recent practice of synthetic modeling. Synthetic models are engineered genetic networks that are implanted in a natural cell environment. Their construction is typically combined with experiments on model organisms as well as mathematical modeling and simulation. What is especially interesting about this combinational modeling practice is that, apart from greater integration between these different epistemic activities, it has also led to the questioning of some central assumptions and notions on which synthetic biology is based. As a result synthetic biology is in the process of becoming more “biology inspired.”     

Synthetic circuits,devices and modules

The aim of synthetic biology is to design artificial biological systems for novel applications. From an engineering perspective, construction of biological systems of defined functionality in a hierarchical way is fundamental to this emerging field. Here, we highlight some current advances on design of several basic building blocks in synthetic biology including the artificial gene control elements, synthetic circuits and their assemblies into devices and modules. Such engineered basic building blocks largely expand the synthetic toolbox and contribute to our understanding of the underlying design principles of living cells.     

A perspective of synthetic biology: assembling building blocks for novel functions

Synthetic biology is a recently emerging field that applies engineering formalisms to design and construct new biological parts, devices, and systems for novel functions or life forms that do not exist in nature. Synthetic biology relies on and shares tools from genetic engineering, bioengineering, systems biology and many other engineering disciplines. It is also different from these subjects, in both insights and approach. Applications of synthetic biology have great potential for novel contributions to established fields and for offering opportunities to answer fundamentally new biological questions. This article does not aim at a thorough survey of the literature and detailing progress in all different directions. Instead, it is intended to communicate a way of thinking for synthetic biology in which basic functional elements are defined and assembled into living systems or biomaterials with new properties and behaviors. Four major application areas with a common theme are discussed and a procedure (or "protocol") for a standard synthetic biology work is suggested.     

合成生物学伦理、法律与社会问题探讨

合成生物学是以基因组学、系统生物学知识和分子生物学技术为基础,综合了科学与工程的一门新兴交叉学科。它使生命科学和生物技术研发进入了以人工设计、合成自然界中原本不曾出现的人造生命体系,以及对这些人工体系进行体内、体外优化,或利用这些人造生命体系研究自然生命规律为目标的新时代。然而,合成生物学研究在迅速发展、表现出巨大潜力和应用前景的同时,也引发了社会各界对相关社会、伦理、安全,以及知识产权等问题的重视与讨论。就世界各国针对合成生命对传统意义上生命概念的挑战、合成生物学产品存在的潜在风险危害、合成生物学研究的风险评估与监管等问题进行回顾综述和相关探讨。