Department of Microbiology, University College Cork, Cork, Ireland.
School of Pharmacy, University College Cork, Cork, Ireland.
Microbiology (Reading). 2012 Jun;158(Pt 6):1389-1401. doi: 10.1099/mic.0.051599-0. Epub 2012 Mar 30.
Isoprenoid biosynthesis is essential for cell survival. Over 35 000 isoprenoid molecules have been identified to date in the three domains of life (bacteria, archaea and eukaryotes), and these molecules are involved in a wide variety of vital biological functions. Isoprenoids may be synthesized via one of two independent nonhomologous pathways, the classical mevalonate pathway or the alternative 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Given that isoprenoids are indispensable, enzymes involved in their production have been investigated as potential drug targets. It has also been observed that the MEP pathway intermediate 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMB-PP) can activate human Vγ9/Vδ2 T cells. Herein we review isoprenoid biosynthesis in bacterial pathogens. The role of isoprenoid biosynthesis pathways in host-pathogen interactions (virulence potential and immune stimulation) is examined. Finally, the design of antimicrobial drugs that target isoprenoid biosynthesis pathways is discussed.
异戊烯基生物合成对于细胞存活至关重要。迄今为止,在生命的三个领域(细菌、古菌和真核生物)中已经鉴定出超过 35000 种异戊烯基分子,这些分子参与了各种各样的重要生物功能。异戊烯基可以通过两种独立的非同源途径之一合成,即经典的甲羟戊酸途径或替代的 2C-甲基-D-赤藓醇 4-磷酸(MEP)途径。鉴于异戊烯基是不可或缺的,因此已将参与其生产的酶作为潜在的药物靶标进行了研究。还观察到 MEP 途径中间体 1-羟基-2-甲基-2-(E)-丁烯基 4-二磷酸(HMB-PP)可以激活人 Vγ9/Vδ2 T 细胞。本文综述了细菌病原体中的异戊烯基生物合成。考察了异戊烯基生物合成途径在宿主-病原体相互作用(毒力潜力和免疫刺激)中的作用。最后,讨论了针对异戊烯基生物合成途径的抗菌药物的设计。