Laboratory of Bacterial Genetics, Faculty of Chemistry, Gdansk University of Technology, 80-233 Gdansk, Poland.
Int J Mol Sci. 2021 Dec 24;23(1):189. doi: 10.3390/ijms23010189.
The outer membrane (OM) of Gram-negative bacteria, such as , is essential for their viability. Lipopolysaccharide (LPS) constitutes the major component of OM, providing the permeability barrier, and a tight balance exists between LPS and phospholipids amounts as both of these essential components use a common metabolic precursor. Hence, checkpoints are in place, right from the regulation of the first committed step in LPS biosynthesis mediated by LpxC through its turnover by FtsH and HslUV proteases in coordination with LPS assembly factors LapB and LapC. After the synthesis of LPS on the inner leaflet of the inner membrane (IM), LPS is flipped by the IM-located essential ATP-dependent transporter to the periplasmic face of IM, where it is picked up by the LPS transport complex spanning all three components of the cell envelope for its delivery to OM. MsbA exerts its intrinsic hydrocarbon ruler function as another checkpoint to transport hexa-acylated LPS as compared to underacylated LPS. Additional checkpoints in LPS assembly are: LapB-assisted coupling of LPS synthesis and translocation; cardiolipin presence when LPS is underacylated; the recruitment of RfaH transcriptional factor ensuring the transcription of LPS core biosynthetic genes; and the regulated incorporation of non-stoichiometric modifications, controlled by the stress-responsive RpoE sigma factor, small RNAs and two-component systems.
革兰氏阴性菌的外膜（OM）对于其生存至关重要，如 。脂多糖（LPS）构成 OM 的主要成分，提供渗透性屏障，LPS 和磷脂的数量之间存在着紧密的平衡，因为这两种必需成分使用共同的代谢前体。因此，从 LPS 生物合成的第一步调节开始就存在着检查点，这是由 LpxC 介导的，通过 FtsH 和 HslUV 蛋白酶与 LPS 组装因子 LapB 和 LapC 的协同作用来完成 LPS 的周转率。在 LPS 在内膜（IM）的内叶上合成后，LPS 被位于 IM 上的必需 ATP 依赖性转运蛋白翻转到 IM 的周质面，在那里它被 LPS 运输复合物捕获，该复合物跨越细胞包膜的所有三个组成部分，将其递送到 OM。与酰化不足的 LPS 相比，MsbA 作为另一个检查点发挥其内在的烃标尺功能来运输六酰化 LPS。LPS 组装中的其他检查点包括：LapB 辅助 LPS 合成和转运的偶联；当 LPS 酰化不足时存在心磷脂；招募 RfaH 转录因子以确保 LPS 核心生物合成基因的转录；以及受应激反应 RpoE σ 因子、小 RNA 和双组分系统控制的非化学计量修饰的调节性掺入。
