Editor: Jose Gil
Daunorubicin efflux in Streptomyces peucetius modulates biosynthesis by feedback regulation
Article first published online: 20 JAN 2010
© 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved
FEMS Microbiology Letters
Volume 305, Issue 1, pages 18–27, April 2010
How to Cite
Srinivasan, P., Palani, S. N. and Prasad, R. (2010), Daunorubicin efflux in Streptomyces peucetius modulates biosynthesis by feedback regulation. FEMS Microbiology Letters, 305: 18–27. doi: 10.1111/j.1574-6968.2010.01905.x
- Issue published online: 4 MAR 2010
- Article first published online: 20 JAN 2010
- Received 12 December 2009; revised 11 January 2010; accepted 12 January 2010.Final version published online 11 February 2010.
- Streptomyces peucetius;
- drug efflux;
- feedback regulation;
Streptomyces peucetius self-resistance genes drrA and drrB encode membrane-associated proteins that function like an ABC transporter for the efflux of daunorubicin and to maintain a constant subinhibitory physiological concentration of the drug within the cell. In this study, the drrA and drrB operons were disrupted for investigating drug production, self-resistance and regulation. The drrA–drrB null mutant was highly sensitive to daunorubicin. A 10-fold decrease in drug production was observed in the null mutant compared with the wild-type strain. We propose that the absence of a drug-specific efflux pump increases the intracellular concentration of daunorubicin, which is sensed by the organism to turn down drug production. Quantitative real-time PCR analysis of the mutant showed a drastic reduction in the expression of the key regulator dnrI and polyketide synthase gene dpsA. However, the expression of regulatory genes dnrO and dnrN was increased. Feedback regulation based on the intracellular daunorubicin concentration is discussed.