Riboswitches reside in the untranslated region of RNA and regulate genes involved in the biosynthesis of essential metabolites through binding of small molecules. Since their discovery at the beginning of this century, riboswitches have been regarded as potential antibacterial targets. Using fragment screening, high-throughput screening and rational ligand design guided by X-ray crystallography, lead compounds against various riboswitches have been identified. Here, we review the current status and suitability of the thiamine pyrophosphate (TPP), flavin mononucleotide (FMN), glmS, guanine, and other riboswitches as antibacterial targets and discuss them in a biological context. Further, we highlight challenges in riboswitch drug discovery and emphasis the need to develop riboswitch specific high-throughput screening methods.

中文翻译：

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核糖开关作为抗生素的药物靶标

核糖开关位于RNA的非翻译区，并通过小分子的结合来调节参与必需代谢物生物合成的基因。自从本世纪初发现以来，核糖开关已被视为潜在的抗菌靶标。使用片段筛选，高通量筛选和X射线晶体学指导的合理配体设计，已确定了针对各种核糖开关的先导化合物。在这里，我们回顾了硫胺素焦磷酸（TPP），黄素单核苷酸（FMN），glmS的现状和适用性，鸟嘌呤和其他核糖开关作为抗菌目标，并在生物学背景下进行讨论。此外，我们强调了核糖开关药物发现中的挑战，并强调了开发核糖开关特定的高通量筛选方法的需要。