Pleiotropic regulation of daptomycin synthesis by DptR1, a LuxR family transcriptional regulator.

Abstract

Daptomycin, produced by Streptomyces roseosporus is a novel cyclic lipopeptide antibiotic for treatment of Gram-positive bacteria caused infections. While, the regulatory mechanism of daptomycin synthesis has not been fully understood. Here we reported that DptR1, a LuxR family transcriptional regulator, played a pleiotropic regulatory role on daptomycin synthesis, for the first time. Deletion or over-expressing of dptR1 decreases the daptomycin's production, increases the transcriptional levels of the core dpt genes of day 3 and decreases the transcriptional levels of the core dpt genes of day 4, sharply, which indicates the transcriptional regulation of DptR1 on daptomycin synthesis is complex and time-ordered. The transcriptional levels of dptR2 increase in dptR1 deletion mutant (DR1), but decrease in dptR1 over-expression mutant (OR1), dramatically, compared to the starting strain of Streptomyces roseosporus N3 (WT), on the 3rd day, which indicates that DptR1 represses the transcription of dptR2. While, the transcriptional levels of dptR3 both in DR1 and OR1 decrease obviously, compared to WT, on the 3rd and 4th day. Comparative analysis of promoters' activities, using xylE gene as the reporter, shows that DptR1 activated the transcription of its own gene of dptR1 and represses the transcription of the dptR3 by affecting the promoter activities. While DptR1 may affect the expression of dptR2 indirectly, not by affecting the promoter activity of dptR2. DptR1, a LuxR family transcriptional regulator, played a pleiotropic regulation role on daptomycin synthesis.