Using microbial co-cultures involving Yarrowia lipolytica to produce sesquiterpenoids

使用涉及解脂耶氏酵母的微生物共培养来生产倍半萜类化合物

• 批准号: 2505903
• 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: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2505903
• 关键词: Using; microbial; co; cultures; involving

The central aim of this project is utilising various biological co-culture engineering and related techniques to achieve high and industrially relevant production of sesquiterpenoids in the yeast Yarrowia lipolytica. Sesquiterpenoids are types of high-value terpenoids with various uses in medicine such as in the treatment of cancer, neurodegenerative diseases, inflammation, wound healing and others. Yarrowia lipolytica has been identified as a potential high producer of terpenoids. Cooperation of different microbial species as well as specialisation within the single-species community are emerging metabolic engineering strategies to increase the biotechnological productivity of microbes. My project contains several steps towards the efficient community-based production of sesquiterpenoids: 1) Use cyanobacteria or algae engineered to secrete sucrose in a community with Yarrowia lipolytica to feed it while consuming a waste product of Yarrowia, CO22) Engineer Yarrowia lipolytica metabolism by genetic modifications to overproduce sesquiterpenoids. The major strategy would be overproducing pathway enzymes leading to the final product and repressing the other pathway branches. 3) Creating a single-species Yarrowia community. Yarrowia produces citric acid as a waste product which decreases the carbon use towards the desired product significantly. However, Yarrowia is also able to utilise citric acid. I aim to engineer both strains to produce the final sesquiterpenoid product but one of the Yarrowia strains consuming the citric acid waste. 4) I would aim to combine the 1st and 2nd point into cyanobacteria-yeast intracellular interaction. Cyanobacteria would be releasing sucrose and sesquiterpenoid intermediates into Yarrowia cytosol to get converted into the final products. 5) Additional avenues to explore: - Computational modelling of community behaviour and application of existing models- Constructing automated directed evolution devices to screen the best performing communities and allow those to adapt further- Analysis of what happens inside the community member cells- Embedding the co-cultures into biomaterials to produce medically-relevant compounds into wounds

该项目的中心目标是利用各种生物共培养工程和相关技术，在解脂耶氏酵母中实现高水平和工业相关的倍半萜类化合物生产。倍半萜类化合物是一类高价值的萜类化合物，在医学中具有各种用途，例如治疗癌症、神经退行性疾病、炎症、伤口愈合等。解脂耶氏酵母是一种潜在的萜类化合物高产菌。不同微生物物种的合作以及单一物种群落内的专业化是新兴的代谢工程策略，以提高微生物的生物技术生产力。我的项目包括几个步骤，以有效的社区为基础的生产倍半萜类化合物：1）使用蓝藻或藻类工程分泌蔗糖在社区与Yarrowia lipolytica喂养它，同时消耗废物的Yarrowia，CO22）工程Yarrowia lipolytica代谢通过遗传修饰，以过量生产倍半萜类化合物。主要的策略是过量生产导致最终产物的途径酶并抑制其他途径分支。3)创建单一物种的耶氏酵母群落。耶氏酵母产生柠檬酸作为废物，这显著减少了对所需产物的碳使用。然而，耶氏酵母也能够利用柠檬酸。我的目标是设计两种菌株来生产最终的倍半萜类产品，但其中一种耶氏酵母菌株消耗柠檬酸废物。4)我的目标是将联合收割机的第1和第2点到蓝藻-酵母细胞内的相互作用。蓝细菌将释放蔗糖和倍半萜类中间产物到耶氏酵母胞质溶胶中，转化为最终产物。5)探索的其他途径：-社区行为的计算建模和现有模型的应用-构建自动定向进化设备以筛选表现最佳的社区并允许这些社区进一步适应-分析社区成员细胞内发生的事情-将共培养物嵌入生物材料中，以在伤口中产生医学相关化合物