Yang Yung-Hun, Song Eunjung, Kim Eun-Jung, Lee Kwangwon, Kim Woo-Seong, Park Sung-Soo, Hahn Ji-Sook, Kim Byung-Gee
School of Chemical and Biological Engineering, Seoul National University, Seoul, South Korea.
Appl Microbiol Biotechnol. 2009 Mar;82(3):501-11. doi: 10.1007/s00253-008-1802-x. Epub 2008 Dec 13.
NdgR (regulator for nitrogen source-dependent growth and antibiotic production), an IclR-like regulator, has been initially identified as a binding protein to the promoters of doxorubicin biosynthetic genes in Streptomyces peucetius by DNA affinity capture assay method. NdgR is well conserved throughout the Streptomyces species and many other bacteria such as Mycobacteria and Corynebacteria. In Streptomyces coelicolor, ndgR deletion mutant showed slow cell growth and defects in differentiation and enhances the production of actinorhodin (ACT) in minimal media containing certain amino acids where wild-type strain could not produce ACT. Although deletion mutant of ndgR showed different antibiotic production in minimal media containing Leu or Gln, it only showed reduced mRNA expression levels of the genes involved in leucine metabolism. Neither NdgR-dependent expression of glnA nor direct binding of NdgR protein to glnA, glnII, and glnR promoters was observed. However, ScbR, which is governed by NdgR shown by gel mobility shift assay, binds to promoter of glnR, suggesting indirect regulation of glutamine metabolism by NdgR. NdgR protein binds to intergenic region of ndgR-leuC, and scbR-scbA involved in gamma-butyrolactone. Two-dimensional gel analysis has shown a global effect of ndgR deletion in protein expression, including up-regulated proteins involved in ACT synthesis and down-regulation of chaperones such as GroEL, GroES, and DnaK. These results suggest a global regulatory role for NdgR in amino acid metabolisms, quorum sensing, morphological changes, antibiotic production, and expression of chaperonines in S. coelicolor.
NdgR（氮源依赖性生长和抗生素生产调节剂）是一种类IclR调节因子，最初通过DNA亲和捕获测定法被鉴定为淡紫链霉菌中阿霉素生物合成基因启动子的结合蛋白。NdgR在整个链霉菌属物种以及许多其他细菌（如分枝杆菌和棒状杆菌）中高度保守。在天蓝色链霉菌中，ndgR缺失突变体显示细胞生长缓慢、分化缺陷，并在含有某些氨基酸的基本培养基中增强了放线紫红素（ACT）的产生，而野生型菌株在该培养基中无法产生ACT。尽管ndgR缺失突变体在含有亮氨酸或谷氨酰胺的基本培养基中显示出不同的抗生素产量，但它仅显示参与亮氨酸代谢的基因的mRNA表达水平降低。未观察到NdgR对glnA的依赖性表达，也未观察到NdgR蛋白与glnA、glnII和glnR启动子的直接结合。然而，凝胶迁移率变动分析表明受NdgR调控的ScbR与glnR启动子结合，这表明NdgR对谷氨酰胺代谢存在间接调控。NdgR蛋白与ndgR - leuC以及参与γ-丁内酯的scbR - scbA的基因间区域结合。二维凝胶分析表明ndgR缺失对蛋白质表达具有全局性影响，包括参与ACT合成的上调蛋白以及伴侣蛋白（如GroEL、GroES和DnaK）的下调。这些结果表明NdgR在天蓝色链霉菌的氨基酸代谢、群体感应、形态变化、抗生素生产以及伴侣蛋白表达中具有全局性调节作用。
