Metabolic engineering of Cupriavidus necator for L-arginine production

Cupriavidus necator 用于生产 L-精氨酸的代谢工程

• 批准号: 1944178
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1944178
• 关键词: Metabolic; engineering; Cupriavidus; necator; arginine

Engineered strains of Corynebacterium glutamicum and Escherichia coli are the workhorses of fermentative amino acid production, a growing industry worth billions. Yet these fermentations rely upon carbon from first-generation biomass feedstocks, which fluctuate in cost and supply.The production of palm oil generates over 30 million tons of carbon-rich waste each year. Together with current methods of fertilisation, these are responsible for at least a third of palm oil greenhouse gas emissions; the equivalent of 60 million tonnes of carbon dioxide.This polluting waste has the potential to be used as a novel feedstock for amino acid fermentation; specifically nitrogen-rich arginine, which is growing in use as a tree fertiliser. Doing so would valorise the waste by recycling its carbon back into plantations, whilst reducing the need for inorganic fertilisers. However, no industrial strain exists for this process.To this end, we aim to engineer a microbial cell factory for the conversion of carbon dioxide to L-arginine. Cupriavidus necator can naturally grow on carbon dioxide and hydrogen, making it an ideal host chassis for this purpose. Using metabolic engineering and synthetic biology strategies, an L-arginine overproducer will be developed and optimised. This will be supported by a complementary range of -omic analyses to provide novel insight into how the biosynthetic pathway is regulated. Once economically viable yields and productivities have been reached, this strain will then be demonstrated at pilot-scale gas fermentation using carbon dioxide as the feedstock.

谷氨酸棒杆菌和大肠杆菌的工程菌株是发酵氨基酸生产的主力，这是一个价值数十亿美元的不断增长的产业。然而，这些发酵过程依赖于第一代生物质原料中的碳，而第一代生物质原料的成本和供应会有所波动。棕榈油的生产每年会产生3000多万吨富含碳的废物。加上目前的施肥方法，这些方法至少占棕榈油温室气体排放量的三分之一，相当于6000万吨二氧化碳。这种污染性废物有可能被用作氨基酸发酵的新原料;特别是富含氮的精氨酸，它正被用作树木肥料。这样做可以通过将碳回收到种植园中来提高废物的价值，同时减少对无机肥料的需求。然而，没有工业菌株存在这个过程。为此，我们的目标是工程微生物细胞工厂的二氧化碳转化为L-精氨酸。钩虫贪铜菌可以在二氧化碳和氢气上自然生长，使其成为理想的宿主。使用代谢工程和合成生物学策略，将开发和优化L-精氨酸过度生产者。这将得到一系列互补的组学分析的支持，以提供对生物合成途径如何调节的新见解。一旦达到经济上可行的产量和生产率，这种菌株将在中试规模的气体发酵中使用二氧化碳作为原料。