Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression.
Roseoflavin is a natural antibacterial compound that binds to FMN riboswitches and regulates gene expression.
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DOI：
10.4161/rna.6.2.7727
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发表时间：
2009-04
期刊：
影响因子：
4.1
通讯作者：
Breaker RR
中科院分区：
文献类型：
--
作者：
Lee ER;Blount KF;Breaker RR
信使RNA中的核糖开关携带称为适体的受体结构域，可以结合代谢物并控制相关基因的表达。革兰氏阳性细菌枯草杆菌具有两个代表一类结合黄素单核苷酸（FMN）的核糖开关。这些核糖开关控制负责核黄素（FMN的前体）生物合成和运输的基因。我们发现，玫瑰黄素，FMN和核黄素的化学类似物，具有抗微生物活性，可以直接结合到FMN核糖开关适体和下调B中的FMN核糖开关-lacZ报告基因的表达。枯草芽孢杆菌核糖开关在玫瑰黄素的抗菌机制中的作用得到了我们的观察的支持，即一些先前鉴定的玫瑰黄素抗性细菌在FMN适体内具有突变。这些耐药细菌中的核糖开关突变破坏了配体结合，并在核黄素或玫瑰黄素存在下抑制报告基因表达。如果FMN核糖开关是玫瑰黄素抗微生物作用的主要靶点，那么未来开发触发FMN核糖开关功能的化合物的努力可能会导致新的抗微生物药物的鉴定。
Riboswitches in messenger RNAs carry receptor domains called aptamers that can bind to metabolites and control expression of associated genes. The Gram-positive bacterium Bacillus subtilis has two representatives of a class of riboswitches that bind flavin mononucleotide (FMN). These riboswitches control genes responsible for the biosynthesis and transport of riboflavin, a precursor of FMN. We found that roseoflavin, a chemical analog of FMN and riboflavin that has antimicrobial activity, can directly bind to FMN riboswitch aptamers and downregulate the expression of an FMN riboswitch-lacZ reporter gene in B. subtilis. A role for the riboswitch in the antimicrobial mechanism of roseoflavin is supported by our observation that some previously identified roseoflavin-resistant bacteria have mutations within an FMN aptamer. Riboswitch mutations in these resistant bacteria disrupt ligand binding and derepress reporter gene expression in the presence of either riboflavin or roseoflavin. If FMN riboswitches are a major target for roseoflavin antimicrobial action, then future efforts to develop compounds that trigger FMN riboswitch function could lead to the identification of new antimicrobial drugs.