Biosynthesis of Membrane Lipids.
Biosynthesis of Membrane Lipids.
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DOI：
10.1128/ecosalplus.3.6.4
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发表时间：
2008-09-01
期刊：
影响因子：
--
通讯作者：
Rock, Charles O
中科院分区：
文献类型：
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作者：
Cronan, John E Jr;Rock, Charles O
大肠杆菌和（很大程度上通过类推）肠沙门氏菌中的途径仍然是细菌脂质合成途径的范例，尽管最近已经证明细菌在脂质合成的特定领域中存在相当大的多样性。脂肪酸合成蛋白质的结构生物学基本上是完整的。然而，磷脂合成的膜结合酶仍然难以进行结构分析。遗传技术的最新进展使得脂质合成的必需基因能够得到严格的测试，并且正如预期的那样，大多数基因在标准生长条件下是必需的。许多基因中都有条件致死突变体，这有利于生理分析。一系列遗传构建体有助于分析其他生物体的基因功能。质谱技术的进步使得能够对脂质成分进行非常准确和详细的分析，并检测脂质生物合成蛋白之间以及与脂质途径之外的蛋白质之间的相互作用。这些进步的结合导致使用大肠杆菌和肠沙门氏菌来发现针对脂质合成的新抗菌剂，并破译已知抗菌剂的分子作用。最后，细菌脂肪酸除了作为膜脂结构成分之外的作用也被揭示。例如，脂肪酸合成在必需酶辅因子、生物素和硫辛酸的合成中起主要作用。尽管细菌脂肪酸的其他作用，例如酰基高丝氨酸群体感应分子的合成，并不是大肠杆菌固有的，但引入相关基因后，这些外来分子的合成很容易进行，并且可用的复杂工具可用于破译这些分子的合成机制。
The pathways in Escherichia coli and (largely by analogy) S. enterica remain the paradigm of bacterial lipid synthetic pathways, although recently considerable diversity among bacteria in the specific areas of lipid synthesis has been demonstrated. The structural biology of the fatty acid synthetic proteins is essentially complete. However, the membrane-bound enzymes of phospholipid synthesis remain recalcitrant to structural analyses. Recent advances in genetic technology have allowed the essentialgenes of lipid synthesis to be tested with rigor, and as expected most genes are essential under standard growth conditions. Conditionally lethal mutants are available in numerous genes, which facilitates physiological analyses. The array of genetic constructs facilitates analysis of the functions of genes from other organisms. Advances in mass spectroscopy have allowed very accurate and detailed analyses of lipid compositions as well as detection of the interactions of lipid biosynthetic proteins with one another and with proteins outside the lipid pathway. The combination of these advances has resulted in use of E. coli and S. enterica for discovery of new antimicrobials targeted to lipid synthesis and in deciphering the molecular actions of known antimicrobials. Finally,roles for bacterial fatty acids other than as membrane lipid structural components have been uncovered. For example, fatty acid synthesis plays major roles in the synthesis of the essential enzyme cofactors, biotin and lipoic acid. Although other roles for bacterial fatty acids, such as synthesis of acyl-homoserine quorum-sensing molecules, are not native to E. coli introduction of the relevant gene(s) synthesis of these foreign molecules readily proceeds and the sophisticated tools available can used to decipher the mechanisms of synthesis of these molecules.