Pleiotropic regulation of daptomycin synthesis by DptR1, a LuxR family transcriptional regulator
Pleiotropic regulation of daptomycin synthesis by DptR1, a LuxR family transcriptional regulator
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LuxR家族转录调节因子DptR1对达托霉素合成的多效性调节
DOI：
10.1007/s11274-020-02909-z
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发表时间：
2020-08
影响因子：
4.1
通讯作者：
Guanghai Yu
中科院分区：
文献类型：
--
作者：
Guanghai Yu
达托霉素是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了解。本文首次报道了LuxR家族转录调控因子DptR1对达托霉素合成的多效性调控作用。dptR1的缺失或过表达使达托霉素的产量下降，第3天的核心基因转录水平显著升高，第4天的核心基因转录水平显著降低，表明DptR1对达托霉素合成的转录调控是复杂的、有时序性的。与出发菌株玫瑰孢链霉菌N3（WT）相比，dptR2的转录水平在第3天增加了indptR1缺失突变体（DR1），而indptR1过表达突变体（OR1）显著降低，表明DptR1抑制了dptR2的转录。而dptR3在DR1和OR1中的转录水平在第3、4天均较WT明显下降。以xylE基因为报告基因，对启动子活性的比较分析表明，DptR1通过影响启动子活性，激活自身基因dptR1的转录，抑制dptR3的转录。而DptR1可能通过间接的方式而不是通过影响dptR2的启动子活性来影响dptR2的表达。
AbstractDaptomycin, produced byStreptomyces roseosporusis 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 ofdptR1decreases the daptomycin’s production, increases the transcriptional levels of the coredptgenes of day 3 and decreases the transcriptional levels of the coredptgenes of day 4, sharply, which indicates the transcriptional regulation of DptR1 on daptomycin synthesis is complex and time-ordered. The transcriptional levels ofdptR2increase indptR1deletion mutant (DR1), but decrease indptR1over-expression mutant (OR1), dramatically, compared to the starting strain ofStreptomyces roseosporusN3 (WT), on the 3rd day, which indicates that DptR1 represses the transcription ofdptR2. While, the transcriptional levels ofdptR3both in DR1 and OR1 decrease obviously, compared to WT, on the 3rd and 4th day. Comparative analysis of promoters’ activities, usingxylEgene as the reporter, showed that DptR1 activated the transcription of its own gene ofdptR1and represses the transcription of thedptR3by affecting the promoter activities. While DptR1 may affect the expression ofdptR2indirectly, not by affecting the promoter activity ofdptR2.Graphic AbstractDptR1, a LuxR family transcriptional regulator, played a pleiotropic regulation role on daptomycin synthesis.
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影响因子：
4.9
作者：
K. Nguyen;Xiaowei He;D. Alexander;Chen Li;J. Gu;Carmela T. M. Mascio;A. V. Van Praagh;L. Mortin;M. Chu;J. Silverman;P. Brian;R. H. Baltz
通讯作者：
K. Nguyen;Xiaowei He;D. Alexander;Chen Li;J. Gu;Carmela T. M. Mascio;A. V. Van Praagh;L. Mortin;M. Chu;J. Silverman;P. Brian;R. H. Baltz
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影响因子：
3
作者：
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通讯作者：
Chen, Yunlin
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影响因子：
5
作者：
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通讯作者：
Chen, Yunlin
影响因子：
5.2
作者：
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通讯作者：
Li YQ
影响因子：
4.4
作者：
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通讯作者：
Peng-Hui Yuan;Ri-Cheng Zhou;Xuepeng Chen;Shuai Luo;Feng Wang;X. Mao;Yong-Quan Li