Fatty acid biosynthesis, the first stage in membrane lipid biogenesis, is catalyzed in most bacteria by a series of small, soluble proteins that are each encoded by a discrete gene (Fig. 1; Table 1). This arrangement is termed the type II fatty acid synthase (FAS) system and contrasts sharply with the type I FAS of eukaryotes which is a dimer of a single large, multifunctional polypeptide. Thus, the bacterial pathway offers several unique sites for selective inhibition by chemotherapeutic agents. The site of action of isoniazid, used in the treatment of tuberculosis for 50 years, and the consumer antimicrobial agent triclosan were revealed recently to be the enoyl-ACP reductase of the type II FAS. The fungal metabolites, cerulenin and thiolactomycin, target the condensing enzymes of the bacterial pathway while the dehydratase/isomerase is inhibited by a synthetic acetylenic substrate analogue. Transfer of fatty acids to the membrane has also been inhibited via interference with the first acyltransferase step, while a new class of drugs targets lipid A synthesis. This review will summarize the data generated on these inhibitors to date, and examine where additional efforts will be required to develop new chemotherapeutics to help combat microbial infections.

中文翻译：

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脂质生物合成作为抗菌剂的目标。

脂肪酸生物合成是膜脂质生物发生的第一步，它在大多数细菌中由一系列小的可溶性蛋白质催化，这些蛋白质各自由离散的基因编码（图1；表1）。这种排列被称为II型脂肪酸合酶（FAS）系统，并且与真核生物的I型FAS形成鲜明对比，该真核生物是单个大的多功能多肽的二聚体。因此，细菌途径为化学治疗剂的选择性抑制提供了几个独特的位点。最近发现，用于治疗结核病50年的异烟肼的作用部位和消费性抗菌剂三氯生是II型FAS的烯酰ACP还原酶。真菌代谢产物，蓝精和硫菌霉素 靶向细菌途径的缩合酶，而脱水酶/异构酶则被合成的炔属底物类似物抑制。通过干扰第一个酰基转移酶步骤，也可以抑制脂肪酸向膜的转移，而一类新的药物针对脂质A的合成。这篇综述将总结迄今为止在这些抑制剂上产生的数据，并检查在哪些地方需要进一步的努力来开发新的化学疗法来帮助抵抗微生物感染。