With the increase of drug resistance caused by the improper use and abuse of antibiotics, human beings are facing a global health crisis. Sequencing of Streptomyces genomes revealed the presence of an important reservoir of secondary metabolic gene clusters for previously unsuspected products with potentially valuable bioactivity. It has therefore become necessary to activate these cryptic pathways through various strategies. Here, we used RNA-seq data to perform a comparative transcriptome analysis of Streptomyces ansochromogenes (wild-type, WT) and its global regulatory gene disruption mutant ΔwblA, in which some differentially expressed genes are associated with the abolished nikkomycin biosynthesis and activated tylosin analogue compounds (TACs) production, and also with the oviedomycin production that is induced by the genetic manipulation of two differentially expressed genes (san7324 and san7324L) encoding RsbR. These results provide a significant clue for the discovery of new drug candidates and the activation of cryptic biosynthetic gene clusters.

中文翻译：

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由无色链霉菌和 ΔwblA 的 RNA-seq 数据引导的隐性抗生素生物合成基因簇的激活

随着抗生素的不当使用和滥用导致耐药性增加，人类正面临着全球性的健康危机。链霉菌基因组的测序揭示了一个重要的次级代谢基因簇库的存在，用于以前未曾怀疑的具有潜在价值的生物活性的产物。因此，有必要通过各种策略激活这些神秘的途径。在这里，我们使用 RNA-seq 数据对 Streptomyces ansochromogenes进行比较转录组分析（野生型，WT）及其全球调控基因破坏突变体 ΔwblA，其中一些差异表达的基因与尼可霉素生物合成的废除和泰乐菌素类似物（TACs）的产生有关，也与由编码 RsbR 的两个差异表达基因（san7324 和 san7324L）的遗传操作。这些结果为发现新的候选药物和激活神秘生物合成基因簇提供了重要线索。