Abstract

The Streptomyces genus comprises Gram-positive bacteria known to produce over two-thirds of the antibiotics used in medical practice. The biosynthesis of these secondary metabolites is highly regulated and influenced by a range of nutrients present in the growth medium. In Streptomyces coelicolor, glucose inhibits the production of actinorhodin (ACT) and undecylprodigiosin (RED) by a process known as carbon catabolite repression (CCR). However, the mechanism mediated by this carbon source still needs to be understood. It has been observed that glucose alters the transcriptomic profile of this actinobacteria, modifying different transcriptional regulators, including some of the one- and two-component systems (TCSs). Under glucose repression, the expression of one of these TCSs SCO6162/SCO6163 was negatively affected. We aimed to study the role of this TCS on secondary metabolite formation to define its influence in this general regulatory process and likely establish its relationship with other transcriptional regulators affecting antibiotic biosynthesis in the Streptomyces genus. In this work, in silico predictions suggested that this TCS can regulate the production of the secondary metabolites ACT and RED by transcriptional regulation and protein–protein interactions of the transcriptional factors (TFs) with other TCSs. These predictions were supported by experimental procedures such as deletion and complementation of the TFs and qPCR experiments. Our results suggest that in the presence of glucose, the TCS SCO6162/SCO6163, named GarR/GarS, is an important negative regulator of the ACT and RED production in S. coelicolor.

Key points

• GarR/GarS is a TCS with domains for signal transduction and response regulation

• GarR/GarS is an essential negative regulator of the ACT and RED production

• GarR/GarS putatively interacts with and regulates activators of ACT and RED

中文翻译：

---

双组分系统 GarR/GarS 在天蓝色链霉菌抗生素生产中的作用概述

摘要

链霉菌属由革兰氏阳性细菌组成，已知可产生超过三分之二的医疗实践中使用的抗生素。这些次生代谢物的生物合成受到生长培养基中存在的一系列营养物质的高度调节和影响。在天蓝色链霉菌中，葡萄糖通过称为碳分解代谢物抑制 (CCR) 的过程抑制放线菌素 (ACT) 和十一烷基灵菌红素 (RED) 的产生。然而，这种碳源介导的机制仍需了解。据观察，葡萄糖改变了这种放线菌的转录组谱，改变了不同的转录调节因子，包括一些单组分和双组分系统（TCS）。在葡萄糖抑制下，这些 TCS SCO6162/SCO6163 之一的表达受到负面影响。我们的目的是研究这种 TCS 对次生代谢物形成的作用，以确定其在这一一般调节过程中的影响，并可能建立其与影响链霉菌属抗生素生物合成的其他转录调节因子的关系。在这项工作中，计算机预测表明，该 TCS 可以通过转录调节以及转录因子 (TF) 与其他 TCS 的蛋白质-蛋白质相互作用来调节次级代谢产物 ACT 和 RED 的产生。这些预测得到了实验程序的支持，例如 TF 的删除和补充以及 qPCR 实验。我们的结果表明，在存在葡萄糖的情况下，TCS SCO6162/SCO6163（称为 GarR/GarS）是S. coelicolor中 ACT 和 RED 产生的重要负调节因子。

关键点

• GarR/GarS 是一种 TCS，具有信号转导和响应调节领域

• GarR/GarS 是 ACT 和 RED 生产的重要负调节因子

• GarR/GarS 可能与 ACT 和 RED 激活剂相互作用并对其进行调节