Phospholipids, the most abundant membrane lipid components, are crucial in maintaining membrane structures and homeostasis for biofunctions. As a structurally diverse and tightly regulated system involved in multiple organelles, phospholipid metabolism is complicated to manipulate. Thus, repurposing phospholipids for lipid-derived chemical production remains unexplored. Herein, we develop a Saccharomyces cerevisiae platform for de novo production of oleoylethanolamide, a phospholipid derivative with promising pharmacological applications in ameliorating lipid dysfunction and neurobehavioral symptoms. Through deregulation of phospholipid metabolism, screening of biosynthetic enzymes, engineering of subcellular trafficking and process optimization, we could produce oleoylethanolamide at a titer of 8,115.7 µg l-1 and a yield on glucose of 405.8 µg g-1. Our work provides a proof-of-concept study for systemically repurposing phospholipid metabolism for conversion towards value-added biological chemicals, and this multi-faceted framework may shed light on tailoring phospholipid metabolism in other microbial hosts.

中文翻译：

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工程酵母磷脂代谢，用于从头生产油酰基乙醇酰胺。

磷脂是最丰富的膜脂质成分，对于维持膜结构和生物功能的动态平衡至关重要。作为涉及多个细胞器的结构多样且受到严格监管的系统，磷脂代谢的操纵非常复杂。因此，将磷脂重新用于脂质衍生的化学生产尚待探索。在本文中，我们开发了酿酒酵母平台，用于从头生产油酰乙醇酰胺，这是一种磷脂衍生物，在减轻脂质功能障碍和神经行为症状方面具有广阔的药理应用。通过放松磷脂代谢的调控，生物合成酶的筛选，亚细胞运输的工程设计和工艺优化，我们可以生产滴度为8,115.7 µg l-1的油酰乙醇酰胺，并获得405的葡萄糖收率。8微克g-1。我们的工作为系统地重新利用磷脂代谢以转化为增值的生物化学物质提供了概念验证研究，并且该多方面的框架可能为在其他微生物宿主中定制磷脂代谢提供了启示。