Engineering synthetic microbial consortia for next-generation biotechnology

自然生态系统由微生物群组成，在这些微生物群中，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使用接种了单一微生物物种的微生物培养，这将原材料和最终产品的加工限制在特定物种的遗传物质所赋予的特性上。随着合成生物学的出现和低成本的DNA化学合成的出现，合成微生物联盟可以用工程微生物物种来设计，以获取遗传多样性和劳动分工的有益属性，就像自然界中发生的那样。在这个项目中，我们的目标是建立必要的工具来合理设计合成微生物联盟，用于工业生物过程应用。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从公开可用的序列数据库中“挖掘”这样的系统，并用一种新的方法来识别没有/最小信号串扰的系统。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。高通量、基于荧光的基因表达分析将用于功能评估。一旦建立了通信设备，我们将确定容易从分工中受益的新陈代谢途径。这些途径将使用先进的DNA组装方法和新的CRISPR工具进行转移，以最大限度地提高燃料、化学品或营养食品等高价值分子的生物产量。合理设计用于工业生物加工应用的微生物联合体的能力可以帮助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过程来实现，在这种过程中，富含遗传成分的合成微生物联合体将允许废物等原材料重新循环回到社会的生产过程中，而不是使用焚烧或掩埋在垃圾填埋场等有害环境的处置替代品。

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.