Modulation of dnrN expression by intracellular levels of DnrO and daunorubicin in Streptomyces peucetius.
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.
Ajithkumar
Vasanthakumar
V
Department of Genetic Engineering, Madurai Kamaraj University, India.
Prasad
Ranjan
R
D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004269:DNA, Bacterial / Q000378:metabolism; D003630:Daunorubicin / Q000378:metabolism*; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D008954:Models, Biological; D011485:Protein Binding; D013302:Streptomyces / Q000502:physiology*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
D001426:Bacterial Proteins; D004269:DNA, Bacterial; C092188:DnrN protein, Streptomyces peucetius; D014157:Transcription Factors; D003630:Daunorubicin