Hesketh Andy, Kock Holger, Mootien Saraspadee, Bibb Mervyn
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK.
Mol Microbiol. 2009 Dec;74(6):1427-44. doi: 10.1111/j.1365-2958.2009.06941.x. Epub 2009 Nov 10.
The availability of zinc was shown to have a marked influence on the biosynthesis of actinorhodin in Streptomyces coelicolor A3(2). Production of actinorhodin and undecylprodigiosin was abolished when a novel pleiotropic regulatory gene, absC, was deleted, but only when zinc concentrations were low. AbsC was shown to control expression of the gene cluster encoding production of coelibactin, an uncharacterized non-ribosomally synthesized peptide with predicted siderophore-like activity, and the observed defect in antibiotic production was found to result from elevated expression of this gene cluster. Promoter regions in the coelibactin cluster contain predicted binding motifs for the zinc-responsive regulator Zur, and dual regulation of coelibactin expression by zur and absC was demonstrated using strains engineered to contain deletions in either or both of these genes. An AbsC binding site was identified in a divergent promoter region within the coelibactin biosynthetic gene cluster, adjacent to a putative Zur binding site. Repression of the coelibactin gene cluster by both AbsC and Zur appears to be required to maintain appropriate intracellular levels of zinc in S. coelicolor.
锌的可利用性对天蓝色链霉菌A3(2)中放线紫红素的生物合成有显著影响。当一个新的多效调控基因absC被缺失时，放线紫红素和十一烷基灵菌红素的产生被消除，但仅在锌浓度较低时。已表明AbsC控制编码天蓝色菌素产生的基因簇的表达，天蓝色菌素是一种未表征的非核糖体合成肽，具有预测的铁载体样活性，并且观察到的抗生素产生缺陷是由该基因簇的表达升高导致的。天蓝色菌素簇中的启动子区域含有锌反应调节因子Zur的预测结合基序，并且使用工程改造为含有这两个基因中一个或两个缺失的菌株证明了zur和absC对天蓝色菌素表达的双重调节。在天蓝色菌素生物合成基因簇内的一个反向启动子区域中，与一个假定的Zur结合位点相邻，鉴定出一个AbsC结合位点。AbsC和Zur对天蓝色菌素基因簇的抑制似乎是维持天蓝色链霉菌细胞内锌的适当水平所必需的。
