Yarrowia lipolytica naturally saves carbon excess as storage lipids. Engineering efforts allow redirecting the high precursor flux required for lipid synthesis towards added-value chemicals such as polyketides, flavonoids, and terpenoids. To redirect precursor flux from storage lipids to other products, four genes involved in triacylglycerol and sterol ester synthesis (DGA1, DGA2, LRO1, ARE1) can be deleted. To elucidate the effect of the deletions on cell physiology and regulation, we performed chemostat cultivations under carbon and nitrogen limitation, followed by transcriptome analysis. We found that storage lipid-free cells show an enrichment of the unfolded protein response, and several biological processes related to protein refolding and degradation are enriched. Additionally, storage lipid-free cells show an altered lipid class distribution with an abundance of potentially cytotoxic free fatty acids under nitrogen limitation. Our findings not only highlight the importance of lipid metabolism on cell physiology and proteostasis, but can also aid the development of improved chassy strains of Y. lipolytica for commodity chemical production.

中文翻译：

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消除储存脂质会诱导解脂耶氏酵母中的蛋白质错误折叠和应激反应

解脂耶氏酵母自然地储存过量的碳作为储存脂质。工程工作可以将脂质合成所需的高前体通量重新导向聚酮化合物、类黄酮和萜类化合物等增值化学品。为了将前体通量从储存脂质重定向到其他产品，可以删除参与三酰甘油和甾醇酯合成的四个基因（DGA1、DGA2、LRO1、ARE1）。为了阐明缺失对细胞生理学和调节的影响，我们在碳和氮限制下进行了恒化器培养，然后进行转录组分析。我们发现，储存的无脂细胞表现出未折叠蛋白质反应的富集，并且与蛋白质重折叠和降解相关的几个生物过程也得到富集。此外，在氮限制下，储存的无脂细胞显示出改变的脂质类别分布，具有丰富的潜在细胞毒性游离脂肪酸。我们的研究结果不仅强调了脂质代谢对细胞生理学和蛋白质稳态的重要性，而且还有助于开发用于商品化学品生产的改良解脂耶氏酵母菌株。