A Synthetic Biology Approach to Accelerating the Engineering of Industrially-Important Organisms

在工业生物技术中，合成生物学和代谢工程是开发可持续化学生产微生物的关键。到目前为止，这些领域主要集中在大肠杆菌和酿酒酵母菌等模式生物上，它们的代谢途径很容易使用当前的工程方法进行优化。然而，许多工业上重要的特性并不存在于模式生物中，而只存在于特殊生物中。这类生物通常没有得到很好的研究，可能生长缓慢，转化频率低，或缺乏遗传工具；因此，它们通常无法通过现有方法进行有效的工程设计。即使在模式生物中，生物合成途径中酶的表达谱也必须仔细优化，因为特征标准部分在新环境中可能表现出不可预测的行为。该研究项目将开发新的合成生物学方法和设计原则，以加速工业相关生物的工程。为了将这些方法应用于非模式生物，我们将重点关注梭状芽胞杆菌，这是一种厌氧菌属，包含几个工业上重要的物种，我们之前已经开发了基础遗传工具。本项目将利用这些工具来实现梭状芽胞杆菌的各种非原生（异种/合成）代谢途径，从而建立和发展设计规则和原则，并产生产生有价值化合物的新菌株。这项研究将涉及设计、DNA合成、DNA组装，以及通过培养厌氧微生物和测量形成的产物来测试代谢途径。

Synthetic biology and metabolic engineering are key to the development of microorganisms for sustainable chemical production in industrial biotechnology. To-date, these fields have focused on model organisms like Escherichia coli and Saccharomyces cerevisiae, in which metabolic pathways are readily optimised using current engineering approaches. However, many industrially-important properties are not found in model organisms, but only in specialist organisms. Such organisms are usually much less well studied and may grow slowly, have low transformation frequencies, or lack genetic tools; so are often not amenable to effective engineering by existing approaches. Even within model organisms, the expression profile of enzymes within biosynthetic pathways must be carefully optimised, as well characterised standard parts can behave unpredictably in new contexts.This research project will develop new synthetic biology approaches and design principles to accelerate the engineering of industrially-relevant organisms. In order to apply these approaches in non-model organisms, we will focus on Clostridium, a genus of anaerobic bacteria containing several industrially-important species, for which we have previously developed foundational genetic tools. This project will exploit and build upon these tools to implement various non-native (heterologous/synthetic) metabolic pathways in Clostridium, allowing the design rules and principles to be established and developed, and resulting in new strains which produce valuable compounds. The research will involve design, DNA synthesis, DNA assembly, and testing of metabolic pathways by the cultivation of anaerobic microorganisms and measurement of products formed.