Department of Genetic Engineering, Madurai Kamaraj University, India.
FEMS Microbiol Lett. 2010 May;306(2):160-7. doi: 10.1111/j.1574-6968.2010.01948.x.
DnrO is a transcription factor that regulates biosynthesis of secondary metabolite daunorubicin (DNR) in Streptomyces peucetius. DNR is a DNA-intercalating drug widely used in cancer chemotherapy. Binding of DnrO close to its promoter fulfils dual functions, namely activation of dnrN and repression of dnrO. DnrN protein binds to a sequence close to the dnrI promoter to activate it, which is essential for turning on biosynthetic genes. In this study, we analyzed the inhibition of DNA-DnrO complex formation by DNR and its effect on dnrO and dnrN expression. The intracellular concentration of drug required to alter the expression of these two genes was determined in vitro. Based on the results, a model is proposed which describes the modulation of dnrN and dnrO expression by intracellular stoichiometric concentration of the drug DNR and protein DnrO. This regulatory mechanism would maintain optimal intracellular drug concentrations in S. peucetius. This would imply that the organism has an adaptive mechanism to escape the cytotoxicity of DNR in addition to its self-resistance.
DnrO 是一种转录因子，可调节链霉菌属中 daunorubicin（DNR）的次生代谢物生物合成。DNR 是一种广泛用于癌症化疗的 DNA 嵌入药物。DnrO 靠近其启动子的结合具有双重功能，即激活 dnrN 和抑制 dnrO。DnrN 蛋白与靠近 dnrI 启动子的序列结合以激活它，这对于打开生物合成基因至关重要。在这项研究中，我们分析了 DNR 对 DNA-DnrO 复合物形成的抑制作用及其对 dnrO 和 dnrN 表达的影响。在体外确定了改变这两个基因表达所需的药物的细胞内浓度。基于这些结果，提出了一个模型，该模型描述了药物 DNR 和蛋白 DnrO 的细胞内化学计量浓度对 dnrN 和 dnrO 表达的调节。这种调节机制将维持链霉菌属中最佳的细胞内药物浓度。这意味着除了自身抗性外，该生物体还有一种适应机制来逃避 DNR 的细胞毒性。
