Wei Junhong, Ma Mengting, Guo Senwen, Xu Yaobo, Xie Jie, Pan Guoqing, Zhou Zeyang
State Key Laboratory of Silkworm Genome Biology, Chongqing Key Laboratory of Microsporidia Infection and Control, Southwest University, Chongqing 400715, China.
College of Sericulture, Textile and Biomass Sciences, Southwest University, Chongqing 400715, China.
Antibiotics (Basel). 2022 Jul 13;11(7):938. doi: 10.3390/antibiotics11070938.
Nigericin is a polyether antibiotic with potent antibacterial, antifungal, antimalarial and anticancer activity. NigR, the only regulator in the nigericin biosynthetic gene cluster in F913, was identified as a SARP family regulator. Disruption of abolished nigericin biosynthesis, while complementation of restored nigericin production, suggesting that NigR is an essential positive regulator for nigericin biosynthesis. Overexpression of in led to significant increase in nigericin production compared to the wild-type strain. Nigericin production in the overexpression strain was found to reach 0.56 g/L, which may be the highest nigericin titer reported to date. Transcriptional analysis suggested that is required for the transcription of structural genes in the gene cluster; quantitative RT-PCR analysis revealed that the expression of structural genes was upregulated in the overexpression strain. Our study suggested that NigR acts in a positive manner to modulate nigericin production by activating transcription of structural genes and provides an effective strategy for scaling up nigericin production.
尼日利亚菌素是一种具有强大抗菌、抗真菌、抗疟疾和抗癌活性的聚醚抗生素。NigR是F913中尼日利亚菌素生物合成基因簇中的唯一调控因子，被鉴定为SARP家族调控因子。对其进行破坏会消除尼日利亚菌素的生物合成，而对其进行互补则会恢复尼日利亚菌素的产生，这表明NigR是尼日利亚菌素生物合成必不可少的正调控因子。与野生型菌株相比，在[具体菌株]中过表达[具体基因]导致尼日利亚菌素产量显著增加。发现过表达菌株中的尼日利亚菌素产量达到0.56 g/L，这可能是迄今为止报道的最高尼日利亚菌素滴度。转录分析表明，[具体基因]对于基因簇中结构基因的转录是必需的；定量RT-PCR分析显示，在[具体基因]过表达菌株中结构基因的表达上调。我们的研究表明，NigR通过激活结构基因的转录以积极方式调节尼日利亚菌素的产生，并为扩大尼日利亚菌素的生产提供了一种有效策略。
