合成生物学技术在材料科学中的应用

材料是人类赖以生存与发展的物质基础,科技和社会的进步都离不开材料技术的发展,未来先进材料的合成和制备必然朝着绿色可持续、低耗高产出、精细可调控、高效多功能的方向发展。以\"基因调控·工程设计\"为核心的合成生物学技术从分子、细胞层面极大地推动了生命科学的发展,也已经并继续为材料科学的发展注入新的思路和活力。本文将围绕合成生物学技术在材料科学中的应用,以基因回路设计为核心,概念应用为线索,重点介绍合成生物学技术在高分子生物材料和无机纳米材料领域的开发和生产,细胞展示和蛋白定向进化战略对分子材料的筛选和优化,\"活体\"功能材料、工程菌调节的人工光合系统功能材料体系以及基因回路在材料科学中的应用。     

哺乳动物合成生物学在生物医学领域的研究进展

虽然合成生物学还处于早期研究阶段,但最近十年,该领域取得了非常显著的研究进展。合成生物学是以工程学思想为基础,通过人工设计、改造基因线路,从而赋予细胞或生物体新的功能,现已广泛应用于各个领域。随着人们对基因线路设计的深入研究,使得合成生物学研究走向临床应用成为可能。本文将围绕哺乳动物合成生物学在疾病治疗方面的研究进展,介绍基因线路的设计思路和方法、不同诱导因子调控的开环式基因线路以及用于疾病诊疗的闭环式基因环路在生物医学领域的应用。最后对合成生物学走向临床治疗的应用前景和挑战进行展望。     

合成生物元件与线路的智能设计

合成生物学是生物学、工程学和计算机科学等多学科交叉融合的新兴前沿领域,旨在通过“自下而上”的工程化设计理念,逐级构建元件、器件和线路,以创造自然界中不存在的人工生物系统,或对已有的生物系统进行目标性改造。随着合成生物产业的飞速发展,对基因线路规模和复杂度的需求也在不断提升。然而,传统依赖经验和试错的方法在元件与线路构建中具有较低的效率和成功率,已无法满足合成生物科技创新转化的需求。这促使元件与线路的开发范式逐渐从人力型、经验型的试错模式向标准化、智能化的工程模式转变。机器学习能够揭示生物数据中隐含的结构和关联,为合成生物元件和线路的智能设计提供强大支持。本文综述了生物元件与线路设计中常用的机器学习算法,以及它们在合成启动子、RNA调控元件、转录因子等生物元件和简单基因线路智能设计中的典型应用,探讨了当前面临的主要挑战及潜在的解决方案。最后,本文展望了机器学习与合成生物系统设计未来的融合趋势,并强调了跨学科合作的重要性。     

The emerging age of cell-free synthetic biology

The engineering of and mastery over biological parts has catalyzed the emergence of synthetic biology. This field has grown exponentially in the past decade. As increasingly more applications of synthetic biology are pursued, more challenges are encountered, such as delivering genetic material into cells and optimizing genetic circuits in vivo. An in vitro or cell-free approach to synthetic biology simplifies and avoids many of the pitfalls of in vivo synthetic biology. In this review, we describe some of the innate features that make cell-free systems compelling platforms for synthetic biology and discuss emerging improvements of cell-free technologies. We also select and highlight recent and emerging applications of cell-free synthetic biology.     

Dynamical roles of biological regulatory circuits

Regulatory circuits are found at the basis of all non-trivial dynamical properties of biological networks. More specifically, positive circuits are involved in the generation of multiple differentiated states, whereas negative circuits can generate cyclic or homeostatic behaviours. These notions are briefly reviewed, from initial biological formulations to mathematical formalisations, further encompassing their application to the design of synthetic regulatory systems. Finally, current challenges for the analysis of increasingly complex regulatory networks are indicated, as well as prospects for our understanding of development and evolution.     

系统生物学和合成生物学研究在生物燃料生产菌株改造中的应用

基于生物质资源生产环境友好的生物燃料,对经济和社会的可持续发展具有重要意义,但其生产成本高的问题十分突出,而高效生产菌株的获得是解决这一问题的根本出路。以下综述了利用系统生物学研究所获得的信息进行菌种改造的过程,重点论述了生产菌株胁迫耐受性方面的研究进展,并讨论了系统生物学、合成生物学和代谢工程技术在改造生物燃料生产菌株中的应用,展望了合成生物学在构建高效生物能源生产菌株方面应用的前景。     

Engineering microbial biofuel tolerance and export using efflux pumps

Many compounds being considered as candidates for advanced biofuels are toxic to microorganisms. This introduces an undesirable trade‐off when engineering metabolic pathways for biofuel production because the engineered microbes must balance production against survival. Cellular export systems, such as efflux pumps, provide a direct mechanism for reducing biofuel toxicity. To identify novel biofuel pumps, we used bioinformatics to generate a list of all efflux pumps from sequenced bacterial genomes and prioritized a subset of targets for cloning. The resulting library of 43 pumps was heterologously expressed in Escherichia coli, where we tested it against seven representative biofuels. By using a competitive growth assay, we efficiently distinguished pumps that improved survival. For two of the fuels (n‐butanol and isopentanol), none of the pumps improved tolerance. For all other fuels, we identified pumps that restored growth in the presence of biofuel. We then tested a beneficial pump directly in a production strain and demonstrated that it improved biofuel yields. Our findings introduce new tools for engineering production strains and utilize the increasingly large database of sequenced genomes.     

Development of GRAS strains for nutraceutical production using systems and synthetic biology approaches: advances and prospects

Nutraceuticals are food substances with medical and health benefits for humans. Limited by complicated procedures, high cost, low yield, insufficient raw materials, resource waste, and environment pollution, chemical synthesis and extraction are being replaced by microbial synthesis of nutraceuticals. Many microbial strains that are generally regarded as safe (GRAS) have been identified and developed for the synthesis of nutraceuticals, and significant nutraceutical production by these strains has been achieved. In this review, we systematically summarize recent advances in nutraceutical research in terms of physiological effects on health, potential applications, drawbacks of traditional production processes, characteristics of production strains, and progress in microbial fermentation. Recent advances in systems and synthetic biology techniques have enabled comprehensive understanding of GRAS strains and its wider applications. Thus, these microbial strains are promising cell factories for the commercial production of nutraceuticals.