Regulation of the Streptomyces coelicolor calcium-dependent antibiotic by absA, encoding a cluster-linked two-component system
Regulation of the Streptomyces coelicolor calcium-dependent antibiotic by absA, encoding a cluster-linked two-component system
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DOI：
10.1128/jb.184.3.794-805.2002
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发表时间：
2002-02-01
影响因子：
3.2
通讯作者：
Champness, WC
中科院分区：
文献类型：
--
作者：
Ryding, NJ;Anderson, TB;Champness, WC
天蓝色链霉菌absA双组分系统最初是通过分析传感器激酶absA 1中的突变来鉴定的，该突变导致该菌株合成的所有四种抗生素的抑制。以前的遗传分析表明，AbsA 2的磷酸化形式在S. coelicolor（T. B。安德森，P.布赖恩和W. C.尚德莫尔Microbiol. 39：553-566，2001）。随后由桑格中心（剑桥，英国）提供的基因组序列数据显示，absA位于生产四种抗生素之一的基因簇内，即钙依赖性抗生素（CDA）。在本文中，我们已经确定了许多转录起始位点内的CDA集群，并已表明，原来的approximatic-negative突变体用于确定absA表现出较强的负调控的启动子上游的拟议CDA生物合成基因比负责生产放线菌紫素和十一烷基灵菌红素的集群中的启动子。相同的抗肿瘤阴性突变体也表现出增加转录从启动子分歧的absA，上游的一个假定的ABC转运蛋白，除了增加转录的absA本身。有趣的是，生物合成转录本的负调控似乎不是由cdaR（编码act和红色簇的通路特异性调节因子的同源物的基因）的转录调控或由与簇相关的任何其他可识别的转录调节因子介导的。absA在调控基因组中不同抗生素生物合成簇的表达中的作用根据其在cda簇中的位置进行了讨论。
The Streptomyces coelicolor absA two-component system was initially identified through analysis of mutations in the sensor kinase absA1 that caused inhibition of all four antibiotics synthesized by this strain. Previous genetic analysis had suggested that the phosphorylated form of AbsA2 acted as a negative regulator of antibiotic biosynthesis in S. coelicolor (T. B. Anderson, P. Brian, and W. C. Champness, Mol. Microbiol. 39:553-566, 2001). Genomic sequence data subsequently provided by the Sanger Centre (Cambridge, United Kingdom) revealed that absA was located within the gene cluster for production of one of the four antibiotics, calcium-dependent antibiotic (CDA). In this paper we have identified numerous transcriptional start sites within the CDA cluster and have shown that the original antibiotic-negative mutants used to identify absA exhibit a stronger negative regulation of promoters upstream of the proposed CDA biosynthetic genes than of promoters in the clusters responsible for production of actinorhodin and undecylprodigiosin. The same antibiotic-negative mutants also showed an increase in transcription from a promoter divergent to that of absA, upstream of a putative ABC transporter, in addition to an increase in transcription of absA itself. Interestingly, the negative regulation of the biosynthetic transcripts did not appear to be mediated by transcriptional regulation of cdaR (a gene encoding a homolog of the pathway-specific regulators of the act and red clusters) or by any other recognizable transcriptional regulator associated with the cluster. The role of absA in regulating the expression of the diverse antibiotic biosynthesis clusters in the genome is discussed in light of its location in the cda cluster.