A key aspect in membrane biogenesis is the coordination of fatty acid to phospholipid synthesis rates. In most bacteria, PlsX is the first enzyme of the phosphatidic acid synthesis pathway, the common precursor of all phospholipids. Previously, we proposed that PlsX is a key regulatory point that synchronizes the fatty acid synthase II with phospholipid synthesis in Bacillus subtilis. However, understanding the basis of such coordination mechanism remained a challenge in Gram‐positive bacteria. Here, we show that the inhibition of fatty acid and phospholipid synthesis caused by PlsX depletion leads to the accumulation of long‐chain acyl‐ACPs, the end products of the fatty acid synthase II. Hydrolysis of the acyl‐ACP pool by heterologous expression of a cytosolic thioesterase relieves the inhibition of fatty acid synthesis, indicating that acyl‐ACPs are feedback inhibitors of this metabolic route. Unexpectedly, inactivation of PlsX triggers a large increase of malonyl‐CoA leading to induction of the fap regulon. This finding discards the hypothesis, proposed for B. subtilis and extended to other Gram‐positive bacteria, that acyl‐ACPs are feedback inhibitors of the acetyl‐CoA carboxylase. Finally, we propose that the continuous production of malonyl‐CoA during phospholipid synthesis inhibition provides an additional mechanism for fine‐tuning the coupling between phospholipid and fatty acid production in bacteria with FapR regulation.

中文翻译：

---

回顾脂肪酸与具有FapR调节作用的细菌中磷脂合成的偶联。

膜生物发生中的关键方面是脂肪酸与磷脂合成速率的协调。在大多数细菌中，PlsX是磷脂酸合成途径中的第一种酶，是所有磷脂的共同前体。以前，我们提出PlsX是使枯草芽孢杆菌中的脂肪酸合酶II与磷脂合成同步的关键调控点。然而，了解这种协调机制的基础仍然是革兰氏阳性细菌的一个挑战。在这里，我们证明了由PlsX耗尽引起的脂肪酸和磷脂合成的抑制导致长链酰基ACP（脂肪酸合酶II的终产物）的积累。通过胞质硫酯酶异源表达水解酰基ACP库可减轻对脂肪酸合成的抑制作用，表明酰基ACP是该代谢途径的反馈抑制剂。出乎意料的是，PlsX的失活会触发丙二酰辅酶A的大量增加，从而导致FAP调节子的诱导。该发现放弃了针对枯草芽孢杆菌提出的假设。酰基-ACPs是乙酰-CoA羧化酶的反馈抑制剂，并扩展到其他革兰氏阳性细菌。最后，我们提出在磷脂合成抑制过程中丙二酰辅酶A的连续生产提供了一种额外的机制，可通过FapR调节来微调细菌中磷脂与脂肪酸生产之间的耦合。