Liu Hui, Zhang Yanyan, Li Shanshan, Wang Jiabin, Wang Xiangjing, Xiang Wensheng
School of Life Sciences, Northeast Agricultural University, Harbin, China.
State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.
Front Bioeng Biotechnol. 2020 Nov 3;8:589730. doi: 10.3389/fbioe.2020.589730. eCollection 2020.
The quorum-sensing system, consisting of an autoregulator synthase (AfsA or Aco homolog) and an autoregulator receptor (ArpA homolog), has been reported to be universally involved in regulating secondary metabolism in streptomycetes. Although the autoregulator synthase is thought to activate antibiotic production, the activation pathway remains poorly understood. ssp. NMWT1 produces nemadectin, which is widely used as a biopesticide and veterinary drug due to its potent nematocidal activity. Here, we identified the Aco/ArpA-like system ScyA1/ScyR1, the ArpA homolog ScyR2 and the AfsA/ArpA-like system ScyA3/ScyR3 as important regulators of nemadectin production in NMWT1. Genetic experiments revealed that these five genes positively regulate nemadectin production, with and having the most potent effects. Importantly, ScyA1 is an upstream regulator of and promotes nemadectin production and sporulation by activating transcription. Intriguingly, silencing in NMWT1 up-regulated 12 of the 17 secondary metabolite biosynthetic core genes present in the NMWT1 genome, suggesting that ScyR1 mainly to be a repressor of secondary metabolism. In conclusion, our findings unveiled the regulatory pathways adopted by the quorum-sensing system, and provided the basis for a method to enhance antibiotic production and to activate the expression of cryptic biosynthetic gene clusters.
群体感应系统由一种自调控合成酶（AfsA或Aco同源物）和一种自调控受体（ArpA同源物）组成，据报道它普遍参与链霉菌次级代谢的调控。尽管自调控合成酶被认为可激活抗生素的产生，但其激活途径仍知之甚少。NMWT1菌株产生奈马克丁，由于其强大的杀线虫活性，奈马克丁被广泛用作生物农药和兽药。在此，我们鉴定出Aco/ArpA样系统ScyA1/ScyR1、ArpA同源物ScyR2以及AfsA/ArpA样系统ScyA3/ScyR3是NMWT1中奈马克丁产生的重要调控因子。遗传实验表明，这五个基因正向调控奈马克丁的产生，其中ScyA1和ScyA3的作用最为显著。重要的是，ScyA1是ScyA3的上游调控因子，通过激活ScyA3的转录来促进奈马克丁的产生和孢子形成。有趣的是，在NMWT1中沉默ScyR1上调了NMWT1基因组中17个次级代谢物生物合成核心基因中的12个，这表明ScyR1主要是次级代谢的抑制因子。总之，我们的研究结果揭示了群体感应系统所采用的调控途径，并为提高抗生素产量和激活隐秘生物合成基因簇表达的方法提供了依据。
