Heath R J, White S W, Rock C O
Protein Science Division, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis TN 38105, USA.
Appl Microbiol Biotechnol. 2002 May;58(6):695-703. doi: 10.1007/s00253-001-0918-z. Epub 2002 Mar 7.
Fatty acid biosynthesis is an emerging target for the development of novel antibacterial chemotherapeutics. The dissociated bacterial system is substantially different from the large, multifunctional protein of mammals, and many possibilities exist for type-selective drugs. Several compounds, both synthetic and natural, target bacterial fatty acid synthesis. Three compounds target the FabI enoyl-ACP reductase step; isoniazid, a clinically used antituberculosis drug, triclosan, a widely used consumer antimicrobial, and diazaborines. In addition, cerulenin and thiolactomycin, two fungal products, inhibit the FabH, FabB and FabF condensation enzymes. Finally, the synthetic reaction intermediates BP1 and decynoyl- N-acetyl cysteamine inhibit the acetyl-CoA carboxylase and dehydratase isomerase steps, respectively. The mechanisms of action of these compounds, as well as the potential development of new drugs targeted against this pathway, are discussed.
脂肪酸生物合成是新型抗菌化疗药物开发的一个新兴靶点。解离的细菌系统与哺乳动物的大型多功能蛋白质有很大不同，因此存在开发类型选择性药物的多种可能性。有几种合成和天然化合物靶向细菌脂肪酸合成。三种化合物靶向FabI烯酰-ACP还原酶步骤；异烟肼，一种临床使用的抗结核药物，三氯生，一种广泛使用的消费用抗菌剂，以及二氮杂硼烷。此外，两种真菌产物浅蓝菌素和硫内酯霉素抑制FabH、FabB和FabF缩合酶。最后，合成反应中间体BP1和癸炔酰-N-乙酰半胱胺分别抑制乙酰辅酶A羧化酶和脱水酶异构酶步骤。本文讨论了这些化合物的作用机制以及针对该途径的新药的潜在开发。
