《生命科学》 2022, 34(9): 1080-1089

类脂A的生物合成研究进展

颜礼娜 , 张郑宇^*

武汉大学药学院，武汉 430071

摘　要：

类脂A 是革兰氏阴性菌细胞壁的重要组成部分，是构成脂多糖疏水基团的主要成分，它不仅可以让脂多糖(lipopolysaccharide, LPS) 锚定在外膜外叶，还可以与Toll 样受体4 (toll-like receptor 4, TLR4) 结合，引起人体的免疫反应。目前研究最为深入的类脂A 合成途径是大肠杆菌(Escherichia coli) 中的Raetz 途径，该合成途径涉及9 种酶，分别是LpxA、LpxC、LpxD、LpxH、LpxB、LpxK、KdtA、LpxL 和LpxM。类脂A 的结构具有保守性，不同种类的革兰氏阴性菌的类脂A 由于不同修饰，在结构上呈现出细微的不同。类脂A 可以越过肠黏膜屏障进入血液，引起致死性败血休克，这使得其成为开发抗菌药物的一个重要靶点。现分别从类脂A 的生物合成、类脂A 生物合成途径中的调控以及类脂A 的生物合成抑制剂三个方面对相关的最新研究进展进行分析与总结。

通讯作者：张郑宇 , Email:hengyu.zhang@whu.edu.cn

Research progress on the lipid A biogenesis

YAN Li-Na , ZHANG Zheng-Yu^*

School of Pharmaceutical Science, Wuhan University, Wuhan 430071, China

Abstract:

Lipid A is the hydrophobic core of lipopolysaccharide, which is the main component of Gram-negative bacterial outer membrane outer leaflet. Lipid A leads to the correct anchoring of LPS into the outer membrane. During bacterial invasion, it is also recognized by TLR4 causing human immune response. In E. coli, the most characterised lipid A synthesis pathway is the Raetz pathway. It involves nine enzymes, namely LpxA, LpxC, LpxD, LpxH, LpxB, LpxK, KdtA, LpxL and LpxM. The structure of lipid A is conserved, and different species of Gramnegative bacteria have subtle differences in their lipid A structure due to their own modifications. Lipid A can cross the intestinal mucosal barrier and enter the bloodstream, causing lethal septic shock, making it an important target for the development of antibacterial drugs. This article briefly introduces the latest research progress in relation to the biogenesis of lipid A, the regulation of lipid A biogenesis and the inhibitors of lipid A biogenesis.

Communication Author：ZHANG Zheng-Yu , Email:hengyu.zhang@whu.edu.cn