Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wroclaw, Poland.
Int J Mol Sci. 2021 Nov 1;22(21):11867. doi: 10.3390/ijms222111867.
bacteria produce a plethora of secondary metabolites including the majority of medically important antibiotics. The onset of secondary metabolism is correlated with morphological differentiation and controlled by a complex regulatory network involving numerous regulatory proteins. Control over these pathways at the molecular level has a medical and industrial importance. Here we describe a GntR-like DNA binding transcription factor SCO3932, encoded within an actinomycete integrative and conjugative element, which is involved in the secondary metabolite biosynthesis regulation. Affinity chromatography, electrophoresis mobility shift assay, footprinting and chromatin immunoprecipitation experiments revealed, both in vitro and in vivo, SCO3932 binding capability to its own promoter region shared with the neighboring gene , as well as promoters of polyketide metabolite genes, such as , a coelimycin biosynthetic gene, and -an activator of actinorhodin biosynthesis. Increased activity of SCO3932 target promoters, as a result of SCO3932 overproduction, indicates an activatory role of this protein in A3(2) metabolite synthesis pathways.
细菌产生大量的次生代谢产物,包括大多数医学上重要的抗生素。次生代谢的开始与形态分化有关,并受涉及众多调节蛋白的复杂调控网络控制。在分子水平上对这些途径的控制具有医学和工业上的重要性。在这里,我们描述了一种 GntR 样 DNA 结合转录因子 SCO3932,它编码在放线菌整合和共轭元件内,参与次生代谢物生物合成的调节。亲和层析、电泳迁移率变动分析、足迹和染色质免疫沉淀实验表明,无论是在体外还是体内,SCO3932 都能够与其自身的启动子区域结合,该区域与邻近基因共享,以及聚酮类代谢物基因的启动子结合,如 coelimycin 生物合成基因和 -actinorhodin 生物合成的激活剂。SCO3932 过表达导致 SCO3932 靶启动子的活性增加,表明该蛋白在 A3(2)代谢物合成途径中具有激活作用。