Advancing the cyanobacterial cell factory: Synechocystis sp. 6803

推进蓝藻细胞工厂：集胞藻属 sp。

• 批准号: 1655062
• 金额: --
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1655062
• 关键词: Advancing; cyanobacterial; cell; factory; Synechocystis

Cyanobacteria are photoautotrophic prokaryotes capable of converting light into chemical energy via oxygenic photosynthesis. This chemical energy is conventionally used to fuel growth and the generation of progeny however, it has been demonstrated that it can be redirected away from growth and used to generate useful carbon-based compounds such as fuels and pharmaceuticals in a renewable manner. Synechocystis sp. 6803 has become a model cyanobacterium in this field as it is unicellular, naturally transformable and possess a fully sequenced and annotated genome. Whilst a variety of carbon based compounds have been successfully produced in Synechocystis, the yields are significantly less than those achieved in Escherichia coli or Saccharomyces cerevisiae. The input costs of engineering specific strains, growing them at scale, harvesting biomass and extracting the product of interest significantly outweigh the value of the desired product. A lack of understanding of the basic cellular process that control and regulate gene expression is responsible for these low yields.This project aims to reveal a more detailed insight into the genome architecture, mechanisms of DNA replication and the regulation of genome copy number in Synechocystis sp. 6803. It is now well understood that Synechocystis is polyploid and the exact number of genome copies per cell fluctuates depending on the growth phase and environmental conditions. However, it is as of yet unknown why the genome copy number fluctuates and how this process is regulated. Furthermore, the chromosome of Synechocystis has an as of yet undescribed origin of replication and some studies in this area have suggested that the DNA replication machinery thought to be ubiquitous to prokaryotes is not essential in Synechocystis. And finally, it is assumed that DNA in prokaryotes is located freely within the cytosol and that genome organisation is a phenomenon reserved only for eukaryotes; an assumption that has yet to be confirmed. Simply constitutively expressing heterologous metabolic pathways has only resulted in genetic instability and a metabolic burden on the host cell. Control over heterologous gene expression is key to achieving high yields of desired products. By revealing the molecular processes by which Synechocystis regulates its genome copy number, initiates DNA replication and organises its genome, this study hopes to provide those working in this field with greater control over how and when heterologous genes are expressed in Synechocystis, thereby improving the notion of a cyanobacterial cell factory.

蓝细菌是一种能够通过光合作用将光能转化为化学能的光合自养原核生物。这种化学能通常用于为生长和后代的产生提供燃料，然而，已经证明，它可以被重新引导远离生长，并用于以可再生的方式产生有用的碳基化合物，例如燃料和药物。集胞藻6803是一种单细胞的、可自然转化的、具有完整测序和注释的基因组的蓝藻，因此成为该领域的模式藻。虽然在集胞藻中已经成功地生产了多种碳基化合物，但产量显著低于在大肠杆菌或酿酒酵母中实现的产量。工程化特定菌株、大规模培养它们、收获生物质和提取感兴趣的产品的投入成本大大超过了所需产品的价值。本项目旨在揭示集胞藻6803的基因组结构、DNA复制机制和基因组拷贝数调控机制。现在很好地理解，集胞藻是多倍体，并且每个细胞的基因组拷贝的确切数量取决于生长阶段和环境条件而波动。然而，目前还不清楚为什么基因组拷贝数波动以及这个过程是如何调节的。此外，集胞藻的染色体有一个尚未描述的复制起点，这方面的一些研究表明，原核生物普遍存在的DNA复制机制在集胞藻中并不重要。最后，假设原核生物中的DNA自由地位于胞质溶胶中，并且基因组组织是仅为真核生物保留的现象;这一假设尚未得到证实。简单地组成型表达异源代谢途径仅导致遗传不稳定性和宿主细胞的代谢负担。对异源基因表达的控制是实现所需产物高产率的关键。通过揭示集胞藻调节其基因组拷贝数，启动DNA复制和组织其基因组的分子过程，这项研究希望为该领域的工作人员提供更大的控制异源基因在集胞藻中表达的方式和时间，从而改善蓝藻细胞工厂的概念。