DptR2, a DeoR-type auto-regulator, is required for daptomycin production in Streptomyces roseosporus

DptR2, a DeoR-type auto-regulator, is required for daptomycin production in Streptomyces roseosporus
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DptR2 是一种 DeoR 型自动调节因子,是玫瑰孢链霉菌生产达托霉素所必需的。

DOI:
10.1016/j.gene.2014.04.044
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发表时间:
2014-07-10
期刊:
影响因子:
3.5
通讯作者:
Li, Yong-Quan
Li, Yong-Quan
中科院分区:
生物学3区
文献类型:
--
作者:
Wang, Feng;Ren, Ni-Ni;Li, Yong-Quan

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达他霉素是由玫瑰孢链霉菌产生的一种新的抗革兰氏阳性菌的环状脂肽抗生素。尽管其生物合成机制、结构改组和发酵优化已被广泛研究,但对其在转录水平上的生产调控知之甚少。我们报道了一个位于S. roseosporus SW 0702是达托霉素生产所必需的,但不是达托霉素基因簇表达所必需的,表明DptR 2不是途径特异性调节剂。此外,EMSA和qRT-PCR分析表明,DptR 2通过与自身启动子结合而受到正性自身调节。同时,通过DNA酶I足迹法测定dptR 2启动子上的结合位点,并评估保护区中的反向互补序列对DptR 2结合的必要性。本研究首次报道了达托霉素在S.玫瑰孢属。(C)© 2014 Elsevier B. V.保留所有权利。
Daptamycin, a novel cyclic lipopeptide antibiotic against Gram-positive bacteria, is produced by Streptomyces roseosporus. Though its biosynthetic mechanism, structural shuffling and fermentation optimization have been extensively studied, little is understood about its production regulation at the transcriptional levels. Here we reported that dptR2, encoding a DeoR-type regulator located close to the daptomycin biosynthesis gene cluster in S. roseosporus SW0702, is required for daptomycin production, but not for the expression of daptomycin gene cluster, suggesting that DptR2 was not a pathway-specific regulator. Furthermore, EMSA and qRT-PCR analysis suggested that DptR2 was positively auto-regulated by binding to its own promoter. Meanwhile, the binding sites on the dptR2 promoter were determined by a DNase I footprinting assay, and the essentiality of the inverted complementary sequences in the protected region for DptR2 binding was assessed. Our results for the first time reported the regulation of daptomycin production at the transcriptional level in S. roseosporus. (C) 2014 Elsevier B.V. All rights reserved.