代谢工程改造解脂耶氏酵母高效合成赤藓糖醇研究进展

Advances in efficient biosynthesis of erythritol by metabolic engineering of Yarrowia lipolytica

摘要:

赤藓糖醇是一种由微生物在高渗胁迫条件下生产的新型四碳糖醇，是良好的代糖产品，同时也是合成多种C4化合物(1,3-丁二烯、1,4-丁二醇、2,5-二氢呋喃等)的平台化合物。与其他多元醇相比，其主要通过生物发酵法生产，因此更具挑战性。解脂耶氏酵母(Yarrowia lipolytica)是合成赤藓糖醇的首选底盘，成为发酵法生产赤藓糖醇的研究热点。目前解脂耶氏酵母工业化生产赤藓糖醇的过程中还存在着亟需突破的瓶颈问题，如合成代谢弱、副产物多以及工业属性不高等。近年来，根据产业化需求定制高版本底盘菌株取得了一定进展，如以葡萄糖和甘油为底物，利用代谢工程改造的解脂耶氏酵母合成赤藓糖醇的最高水平分别达196 g/L和150 g/L，但难以进一步突破菌株生产上限。本文综述了解脂耶氏酵母代谢工程改造合成赤藓糖醇的研究进展，从代谢合成途径、模块化代谢工程改造以及辅助策略提升工业属性等方面，系统分析了解脂耶氏酵母发酵法生产赤藓糖醇的代谢路径及改造策略，为增强解脂耶氏酵母生产赤藓糖醇的研究工作提供一定的研究思路。

Abstract:

Erythritol is a novel 4-carbon sugar alcohol produced by microbes in the presence of hyper-osmotic stress. It has excellent potential to serve as an alternative sugar for people with diabetes and also a platform compound for synthesizing various C4 compounds, such as 1,3-butadiene, 1,4-butanediol, 2,5-dihydrofuran and so on. Compared with other polyols, the fermentative production of erythritol is more challenging. Yarrowia lipolytica is the preferred chassis of erythritol biosynthesis for its high-titer and high-productivity. At present, there are still some bottlenecks in the production of erythritol by Y. lipolytica, such as weak metabolic activity, abundant by-products, and low industrial attributes. Progress has been made in tailoring high version strains according to industrial needs. For example, the highest titer of erythritol produced by the metabolically engineered Y. lipolytica reached 196 g/L and 150 g/L, respectively, by using glucose or glycerol as the carbon sources. However, further improving its production performance becomes challenging. This review summarizes the research progress in the synthesis of erythritol by Y. lipolytica from the perspectives of erythritol producing strains, metabolic pathways, modular modifications, and auxiliary strategies to enhance the industrial properties of the engineered strain. Key nodes in the metabolic pathway and their combination strategies are discussed to guide the research on promoting the production of erythritol by Y. lipolytica.