Regulation of a Novel Gene Cluster Involved in Secondary Metabolite Production in Streptomyces coelicolor
Regulation of a Novel Gene Cluster Involved in Secondary Metabolite Production in Streptomyces coelicolor
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DOI：
10.1128/jb.00681-10
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发表时间：
2010-10-01
影响因子：
3.2
通讯作者：
Elliot, Marie A.
中科院分区：
文献类型：
--
作者：
Hindra;Pak, Patricia;Elliot, Marie A.
抗生素在链霉菌中的生物合成是一个复杂且高度调控的过程。在这里，我们提供了一个新的遗传位点的贡献，在天蓝色链霉菌抗生素生产的证据。过表达的基因簇，包括四个蛋白质编码基因（abeABCD）和反义RNA编码基因（α-abeA）刺激生产的蓝色色素代谢产物放线菌紫素在固体培养基上。放线菌紫素的生产也增强了一个相邻的基因（abeR）编码的预测链霉菌抗生素调节蛋白（SARP）的过表达，而该基因的缺失受损放线菌紫素的生产。我们发现abe基因在多个水平上受到差异调控。abeA的上游是一个启动子，它指导abeABCD在低水平但组成型水平上的转录。然而，abeBCD的表达，显着上调的时间，正好与空中开发的开始和继发性代谢的发病，这种表达被激活的AbeR的结合，四个七聚体重复abeA内的启动子上游。与abeBCD启动子不同的是α-abeA，它的表达与abeBCD的表达相对应，但不需要AbeR的激活。相反，α-abeA转录物水平受双链特异性RNA酶（RNA酶III）的阴性对照。
Antibiotic biosynthesis in the streptomycetes is a complex and highly regulated process. Here, we provide evidence for the contribution of a novel genetic locus to antibiotic production in Streptomyces coelicolor. The overexpression of a gene cluster comprising four protein-encoding genes (abeABCD) and an antisense RNA-encoding gene (alpha-abeA) stimulated the production of the blue-pigmented metabolite actinorhodin on solid medium. Actinorhodin production also was enhanced by the overexpression of an adjacent gene (abeR) encoding a predicted Streptomyces antibiotic regulatory protein (SARP), while the deletion of this gene impaired actinorhodin production. We found the abe genes to be differentially regulated and controlled at multiple levels. Upstream of abeA was a promoter that directed the transcription of abeABCD at a low but constitutive level. The expression of abeBCD was, however, significantly upregulated at a time that coincided with the initiation of aerial development and the onset of secondary metabolism; this expression was activated by the binding of AbeR to four heptameric repeats upstream of a promoter within abeA. Expressed divergently to the abeBCD promoter was alpha-abeA, whose expression mirrored that of abeBCD but did not require activation by AbeR. Instead, alpha-abeA transcript levels were subject to negative control by the double-strand-specific RNase, RNase III.