State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
Sci China Life Sci. 2023 Mar;66(3):612-625. doi: 10.1007/s11427-022-2199-1. Epub 2023 Jan 4.
Genome sequencing has revealed that actinomycetes possess the potential to produce many more secondary metabolites than previously thought. The existing challenge is to devise efficient methods to activate these silent biosynthetic gene clusters (BGCs). In Streptomyces ansochromogenes, disruption of wblA, a pleiotropic regulatory gene, activated the expression of cryptic tylosin analogues and abolished nikkomycin production simultaneously. Overexpressing pathway-specific regulatory genes tylR1 and tylR2 can also trigger the biosynthesis of silent tylosin analogues, in which TylR1 exerted its function via enhancing tylR2 expression. Bacterial one-hybrid system experiments unveiled that WblA directly inhibits the transcription of tylR1 and tylR2 to result in the silence of tylosin analogues BGC. Furthermore, WblA can activate the nikkomycin production through up-regulating the transcription of pleiotropic regulatory gene adpA. More interestingly, AdpA can activate sanG (an activator gene in nikkomycin BGC) but repress wblA. Our studies provide a valuable insight into the complex functions of pleiotropic regulators.
基因组测序表明，放线菌产生的次生代谢产物比之前认为的要多得多。目前的挑战是设计有效的方法来激活这些沉默的生物合成基因簇（BGC）。在变铅青链霉菌中，破坏多效调节基因 wblA 可同时激活隐性泰乐菌素类似物的表达并抑制尼可霉素的产生。过表达途径特异性调节基因 tylR1 和 tylR2 也可以触发沉默的泰乐菌素类似物的生物合成，其中 TylR1 通过增强 tylR2 的表达来发挥作用。细菌单杂交系统实验表明，WblA 直接抑制 tylR1 和 tylR2 的转录，导致泰乐菌素类似物 BGC 的沉默。此外，WblA 可以通过上调多效调节基因 adpA 的转录来激活尼可霉素的产生。更有趣的是，AdpA 可以激活 nikkomycin BGC 中的激活基因 sanG，但抑制 wblA。我们的研究为多效调节因子的复杂功能提供了有价值的见解。
