College of Biological Engineering, Henan University of Technology, Zhengzhou, 450001, People's Republic of China.
World J Microbiol Biotechnol. 2020 Aug 11;36(9):135. doi: 10.1007/s11274-020-02909-z.
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.
达托霉素是由玫瑰孢链霉菌产生的一种新型环状脂肽类抗生素，用于治疗革兰氏阳性菌引起的感染。然而，达托霉素合成的调控机制尚未完全阐明。在这里，我们首次报道了 LuxR 家族转录调节因子 DptR1 对达托霉素合成具有多效调控作用。dptR1 的缺失或过表达会降低达托霉素的产量，显著增加第 3 天核心 dpt 基因的转录水平，并降低第 4 天核心 dpt 基因的转录水平，这表明 DptR1 对达托霉素合成的转录调控是复杂和有序的。与玫瑰孢链霉菌 N3（WT）起始菌株相比，dptR1 缺失突变体（DR1）中 dptR2 的转录水平在第 3 天显著增加，而 dptR1 过表达突变体（OR1）中 dptR2 的转录水平显著降低，这表明 DptR1 抑制 dptR2 的转录。然而，在第 3 天和第 4 天，DR1 和 OR1 中 dptR3 的转录水平均明显低于 WT。使用 xylE 基因作为报告基因进行启动子活性的比较分析表明，DptR1 通过影响启动子活性来激活自身基因 dptR1 的转录，并抑制 dptR3 的转录。而 DptR1 可能通过影响 dptR2 的启动子活性间接影响 dptR2 的表达，而不是直接影响 dptR2 的表达。LuxR 家族转录调节因子 DptR1 对达托霉素合成具有多效调控作用。
