Wright H Tonie, Reynolds Kevin A
Department of Biochemistry and Institute of Structural Biology and Drug Discovery, Virginia Commonwealth University, 800 E. Leigh St. Suite 212, Richmond, VA 23219-1540, USA.
Curr Opin Microbiol. 2007 Oct;10(5):447-53. doi: 10.1016/j.mib.2007.07.001. Epub 2007 Aug 17.
The fatty acid biosynthesis pathway is an attractive but still largely unexploited target for the development of new antibacterial agents. The extended use of the antituberculosis drug isoniazid and the antiseptic triclosan, which are inhibitors of fatty acid biosynthesis, validates this pathway as a target for antibacterial development. Differences in subcellular organization of the bacterial and eukaryotic multienzyme fatty acid synthase systems offer the prospect of inhibitors with host versus target specificity. Platensimycin, platencin, and phomallenic acids, newly discovered natural product inhibitors of the condensation steps in fatty acid biosynthesis, represent new classes of compounds with antibiotic potential. An almost complete catalog of crystal structures for the enzymes of the type II fatty acid biosynthesis pathway can now be exploited in the rational design of new inhibitors, as well as the recently published crystal structures of type I FAS complexes.
脂肪酸生物合成途径是开发新型抗菌剂的一个有吸引力但仍未得到充分利用的靶点。抗结核药物异烟肼和防腐剂三氯生的广泛使用，它们都是脂肪酸生物合成的抑制剂，证实了该途径作为抗菌药物开发靶点的可行性。细菌和真核多酶脂肪酸合成酶系统在亚细胞组织上的差异为开发具有宿主与靶点特异性的抑制剂提供了前景。扁枝衣霉素、扁枝菌素和异戊二烯脂肪酸，这些新发现的脂肪酸生物合成缩合步骤的天然产物抑制剂，代表了具有抗生素潜力的新型化合物。现在，II型脂肪酸生物合成途径中酶的晶体结构几乎完整目录可用于新抑制剂的合理设计，以及最近发表的I型脂肪酸合成酶复合物的晶体结构。
