Payne D J., Warren P V., Holmes D J., Ji Y, Lonsdale J T.
Antimicrobials and Host Defence, 1250 South Collegeville Road, 19426, Collegeville, PA, USA
Drug Discov Today. 2001 May 1;6(10):537-544. doi: 10.1016/s1359-6446(01)01774-3.
In this review we demonstrate how the interplay of genomics, bioinformatics and genomic technologies has enabled an in-depth analysis of the component enzymes of the bacterial fatty-acid biosynthesis pathway as a source of novel antibacterial targets. This evaluation has revealed that many of the enzymes are potentially selective, broad-spectrum antibacterial targets. We also illustrate the suitability of some of these targets for HTS. Furthermore, we discuss how the availability of a robust selectivity assay, mode-of-action assays and numerous crystal structures provide an excellent set of tools with which to initiate integrated programs of research to identify novel antibiotics targeted at these enzymes.
在本综述中，我们展示了基因组学、生物信息学和基因组技术之间的相互作用如何促成了对细菌脂肪酸生物合成途径中的组成酶进行深入分析，将其作为新型抗菌靶点的来源。这一评估表明，许多酶都有可能成为选择性、广谱抗菌靶点。我们还举例说明了其中一些靶点适用于高通量筛选。此外，我们讨论了强大的选择性测定法、作用机制测定法以及众多晶体结构的可用性如何提供了一套出色的工具，用以启动综合研究项目，以鉴定针对这些酶的新型抗生素。
