Jiang Wei, Li Chao, Li Yanjun, Peng Huadong
Department of Chemical and Biological Engineering, Monash University, Clayton, VIC 3800, Australia.
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
J Fungi (Basel). 2022 Apr 21;8(5):427. doi: 10.3390/jof8050427.
Microbial lipids have been a hot topic in the field of metabolic engineering and synthetic biology due to their increased market and important applications in biofuels, oleochemicals, cosmetics, etc. This review first compares the popular hosts for lipid production and explains the four modules for lipid synthesis in yeast, including the fatty acid biosynthesis module, lipid accumulation module, lipid sequestration module, and fatty acid modification module. This is followed by a summary of metabolic engineering strategies that could be used for enhancing each module for lipid production. In addition, the efforts being invested in improving the production of value-added fatty acids in engineered yeast, such as cyclopropane fatty acid, ricinoleic acid, gamma linoleic acid, EPA, and DHA, are included. A discussion is further made on the potential relationships between lipid pathway engineering and consequential changes in cellular physiological properties, such as cell membrane integrity, intracellular reactive oxygen species level, and mitochondrial membrane potential. Finally, with the rapid development of synthetic biology tools, such as CRISPR genome editing tools and machine learning models, this review proposes some future trends that could be employed to engineer yeast with enhanced intracellular lipid production while not compromising much of its cellular health.
由于微生物脂质市场的增长及其在生物燃料、油脂化学品、化妆品等领域的重要应用，它已成为代谢工程和合成生物学领域的热门话题。本综述首先比较了用于脂质生产的常见宿主，并解释了酵母中脂质合成的四个模块，包括脂肪酸生物合成模块、脂质积累模块、脂质隔离模块和脂肪酸修饰模块。接下来总结了可用于增强每个脂质生产模块的代谢工程策略。此外，还介绍了为提高工程酵母中增值脂肪酸（如环丙烷脂肪酸、蓖麻油酸、γ-亚麻酸、二十碳五烯酸和二十二碳六烯酸）产量所做的努力。进一步讨论了脂质途径工程与细胞生理特性（如细胞膜完整性、细胞内活性氧水平和线粒体膜电位）的相应变化之间的潜在关系。最后，随着CRISPR基因组编辑工具和机器学习模型等合成生物学工具的快速发展，本综述提出了一些未来趋势，可用于构建细胞内脂质产量提高而又不严重损害其细胞健康的酵母。
