Phosphatidylcholine (PC) is an abundant membrane lipid component in most eukaryotes, including yeast, and has been assigned multiple functions in addition to acting as building block of the lipid bilayer. Here, by isolating S. cerevisiae suppressor mutants that exhibit robust growth in the absence of PC, we show that PC essentiality is subject to cellular evolvability in yeast. The requirement for PC is suppressed by monosomy of chromosome XV or by a point mutation in the ACC1 gene encoding acetyl-CoA carboxylase. Although these two genetic adaptations rewire lipid biosynthesis in different ways, both decrease Acc1 activity, thereby reducing average acyl chain length. Consistently, soraphen A, a specific inhibitor of Acc1, rescues a yeast mutant with deficient PC synthesis. In the aneuploid suppressor, feedback inhibition of Acc1 through acyl-CoA produced by fatty acid synthase (FAS) results from upregulation of lipid synthesis. The results show that budding yeast regulates acyl chain length by fine-tuning the activities of Acc1 and FAS and indicate that PC evolved by benefitting the maintenance of membrane fluidity.

中文翻译：

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膜脂酰基链的缩短补偿了胆碱营养缺陷型酵母中磷脂酰胆碱的缺乏

磷脂酰胆碱 (PC) 是大多数真核生物（包括酵母）中丰富的膜脂成分，除了充当脂双层的构建块外，还具有多种功能。在这里，通过分离在没有 PC 的情况下表现出强劲增长的酿酒酵母抑制突变体，我们表明 PC 的必要性受酵母细胞可进化性的影响。对 PC 的需求被 XV 染色体单体或ACC1 中的点突变抑制编码乙酰辅酶A羧化酶的基因。尽管这两种遗传适应以不同的方式重新连接脂质生物合成，但都降低了 Acc1 的活性，从而降低了平均酰基链长度。一直以来，Acc1 的特异性抑制剂 soraphen A 可以挽救 PC 合成缺陷的酵母突变体。在非整倍体抑制因子中，通过脂肪酸合成酶 (FAS) 产生的酰基辅酶 A 对 Acc1 的反馈抑制是脂质合成上调的结果。结果表明，出芽酵母通过微调 Acc1 和 FAS 的活性来调节酰基链长度，并表明 PC 通过有利于维持膜流动性而进化。