Synthetic Biology for Fundamental Biochemical Discovery
Synthetic Biology for Fundamental Biochemical Discovery
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DOI：
10.1021/acs.biochem.8b00915
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发表时间：
2019-03-19
期刊：
影响因子：
2.9
通讯作者：
Keasling, Jay D.
中科院分区：
文献类型：
--
作者：
Budin, Itay;Keasling, Jay D.
合成生物学家已经开发出复杂的分子和遗传工具来设计细胞的新生化功能。这些工具的应用侧重于能源和医学中的重要问题，但它们也可以用于解决经典方法无法轻易获取的基础科学主题。我们专注于最近利用合成生物学方法的工作，从启动子工程到细胞部分的从头合成，以研究广泛的生化和细胞问题。这些努力获得的见解包括脂肪酸组成如何调节细胞新陈代谢，转录电路如何作用于稳定多细胞网络，以及选择遗传调控元件所涉及的适应性权衡。我们还强调了关于“通过综合发现”方法如何帮助基础研究的共同主题。例如，通过代谢工程重新连接天然新陈代谢是研究生物分子的有力工具，生物分子的确切组成和丰度是发挥功能的关键。与此同时，合成细胞及其成分的努力使科学家能够解决进化问题，否则这些问题会受到现有实验室模型的限制。
Synthetic biologists have developed sophisticated molecular and genetic tools to engineer new biochemical functions in cells. Applications for these tools have focused on important problems in energy and medicine, but they can also be applied to address basic science topics that cannot be easily accessed by classical approaches. We focus on recent work that has utilized synthetic biology approaches, ranging from promoter engineering to the de novo synthesis of cellular parts, to investigate a wide range of biochemical and cellular questions. Insights obtained by these efforts include how fatty acid composition mediates cellular metabolism, how transcriptional circuits act to stabilize multicellular networks, and fitness trade-offs involved in the selection of genetic regulatory elements. We also highlight common themes about how "discovery by synthesis" approaches can aid fundamental research. For example, rewiring of native metabolism through metabolic engineering is a powerful tool for investigating biological molecules whose exact composition and abundance are key for function. Meanwhile, endeavors to synthesize cells and their components allow scientists to address evolutionary questions that are otherwise constrained by extant laboratory models.