Engineering synthetic microbial consortia for next-generation biotechnology

自然生态系统由微生物群体组成，其中整体遗传生物多样性允许有效利用栖息地资源。相比之下，工业生物加工应用目前采用接种有单一微生物物种的微生物培养物，这将原材料和最终产品的加工限制于由一个特定物种的遗传物质赋予的特性。随着合成生物学的出现和DNA的低成本化学合成的可用性，合成微生物财团可以与工程微生物物种一起设计，以类似于自然界中发生的方式捕获遗传多样性和劳动分工的有益特性。在这个项目中，我们的目标是建立用于工业生物过程应用的合成微生物聚生体的合理设计所必需的工具。作为综合设计过程的一部分，我们将提取自然界中发现的细胞间通信系统。特别是，我们将使用生物信息学工具来“挖掘”这样的系统，从公开的序列数据库与一种新的方法来识别系统，表现出没有/最小的信号串扰。然后，我们将使用合成生物学技术从生物信息学数据中生产细胞间通信设备。将使用高通量、基于荧光的基因表达试验评估功能。一旦建立了通信设备，我们将确定易于从劳动分工中受益的代谢途径。这些途径将通过先进的DNA组装方法和新型CRISPR工具进行转移，以最大限度地提高燃料、化学品或营养品等高价值分子的生物生产。合理设计工业生物加工应用微生物财团的能力有助于实现更可持续的未来。这可以通过在化学品和其他分子的制造中使用生物工艺来实现，其中富含基因内容的合成微生物聚生体将允许将废物等原始资源再循环回社会的生产过程，而不是采用对环境有害的处置办法，如焚烧或填埋。

Natural ecosystems are composed of cohorts of microorganisms where the ensemble genetic biodiversity allows efficient utilisation of habitat resources. In contrast, industrial bioprocessing applications currently employ microbial cultures inoculated with a single microbial species, which limits processing of raw materials and end products to the properties conferred by the genetic material of one particular species. With the advent of Synthetic Biology and the availability of low-cost chemical synthesis of DNA, synthetic microbial consortia can be designed with engineered microbial species to capture the beneficial properties of genetic diversity and division of labour in a similar way to what is happening in nature.In this project, we aim to build the tools necessary for the rational design of synthetic microbial consortia for use in industrial bioprocess applications. As part of an integrated design process, we will extract cell-cell communication systems found in nature. In particular, we will use bioinformatics tools to "mine" such systems from publicly available sequence databases with a novel approach for the identification of systems that exhibit no/minimal signal cross-talk. We will then use synthetic biology technologies to produce cell-to-cell communication devices from the bioinformatics data. High-throughput, fluorescence-based gene expression assays will be used for the assessment of functionality. Once the communication devices are established, we will identify metabolic pathways that are susceptible to benefit from a division of labour. Such pathways will be transferred using advanced DNA assembly methods and novel CRISPR tools to maximise the bioproduction of high-value molecules such as fuels, chemicals or nutraceuticals.The ability to rationally design microbial consortia for industrial bioprocessing applications can aid efforts for a more sustainable future. This can be achieved through the use of bio-based processes in the manufacturing of chemicals and other molecules where synthetic microbial consortia rich in genetic content will allow the re-cycling of raw resources such as wastes back into the productive processes of society rather than environmentally harmful disposal alternatives such as incineration or burying in landfills.