Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Enviroment and Bio-Resource of Three Gorges Area, School of Life Sciences, Southwest University, Beibei Chongqing, 400715, China.
Int J Biol Sci. 2011 Jan 9;7(1):41-52. doi: 10.7150/ijbs.7.41.
Drug resistance of pathogens has necessitated the identification of novel targets for antibiotics. Thiamin (vitamin B1) is an essential cofactor for all organisms in its active form thiamin diphosphate (ThDP). Therefore, its metabolic pathways might be one largely untapped source of antibiotics targets. This review describes bacterial thiamin biosynthetic, salvage, and transport pathways. Essential thiamin synthetic enzymes such as Dxs and ThiE are proposed as promising drug targets. The regulation mechanism of thiamin biosynthesis by ThDP riboswitch is also discussed. As drug targets of existing antimicrobial compound pyrithiamin, the ThDP riboswitch might serves as alternative targets for more antibiotics.
病原体的耐药性使得人们有必要寻找新的抗生素靶标。硫胺素(维生素 B1)在其活性形式硫胺素二磷酸(ThDP)中是所有生物体必需的辅酶。因此,其代谢途径可能是抗生素靶标尚未充分开发的来源之一。本综述描述了细菌硫胺素的生物合成、回收和运输途径。重要的硫胺素合成酶,如 Dxs 和 ThiE,被认为是有前途的药物靶点。还讨论了 ThDP 核糖开关对硫胺素生物合成的调节机制。作为现有抗微生物化合物吡硫醇的药物靶点,ThDP 核糖开关可能成为更多抗生素的替代靶标。