Abstract：
PAS-LuxR transcriptional regulators are conserved proteins governing polyene antifungal biosynthesis. PteF is the regulator of filipin biosynthesis from Streptomyces avermitilis. Its mutation drastically abates filipin, but also oligomycin production, a macrolide ATP-synthase inhibitor, and delays sporulation; thus, it has been considered a transcriptional activator. Transcriptomic analyses were performed in S. avermitilis DpteF and its parental strain. Both strains were grown in a YEME medium without sucrose, and the samples were taken at exponential and stationary growth phases. A total of 257 genes showed an altered expression in the mutant, most of them at the exponential growth phase. Surprisingly, despite PteF being considered an activator, most of the genes affected showed overexpression, thereby suggesting a negative modulation. The affected genes were related to various metabolic processes, including genetic information processing; DNA, energy, carbohydrate, and lipid metabolism; morphological differentiation; and transcriptional regulation, among others, but were particularly related to secondary metabolite biosynthesis. Notably, 10 secondary metabolite gene clusters out of the 38 encoded by the genome showed altered expression profiles in the mutant, suggesting a regulatory role for PteF that is wider than expected. The transcriptomic results were validated by quantitative reverse-transcription polymerase chain reaction. These findings provide important clues to understanding the intertwined regulatory machinery that modulates antibiotic biosynthesis in Streptomyces.
摘要：
PAS-LuxR转录调节因子是控制多烯抗真菌生物合成的保守蛋白。PteF是阿维链霉菌中filipin生物合成的调节剂。它的突变大大减弱了filipin，还有寡霉素的生产，大环内酯ATP合成酶抑制剂，并延迟孢子形成；因此，它被认为是转录激活因子。在阿维米提菌DpteF及其亲本菌株中进行转录组学分析。两种菌株均在不含蔗糖的YEME培养基中生长，样品是在指数和固定生长期采集的。共有257个基因在突变体中显示表达改变，他们中的大多数处于指数增长阶段。令人惊讶的是,尽管PteF被认为是激活剂，大多数受影响的基因显示过表达，从而暗示了负调制。受影响的基因与各种代谢过程有关，包括基因信息处理；DNA，能源,碳水化合物，和脂质代谢；形态分化；和转录调控，其中,但与次生代谢产物的生物合成特别相关。值得注意的是,基因组编码的38个次级代谢物基因簇中的10个在突变体中显示出改变的表达谱,表明PteF的调节作用比预期的要宽。通过定量逆转录聚合酶链反应验证转录组结果。这些发现为理解链霉菌中调节抗生素生物合成的相互交织的调控机制提供了重要线索。
