Kim Dong-Gyun, Kim Gyu Min, Oh Dong Nyoung, Kim Young-Sam, Lee Jong Min
Biotechnology Research Division, National Institute of Fisheries Science, Busan, Republic of Korea.
Department of Biotechnology, Pukyong National University, Busan, 48513, Republic of Korea.
Sci Rep. 2025 Jul 1;15(1):21372. doi: 10.1038/s41598-025-98559-y.
This study presents the identification and characterization of the promoter region of Vibrio anguillarum NB10, which enhances the expression of FK506-binding protein (FKBP)-type peptidyl-prolyl cis/trans isomerase (PPIase; FklB), capable of binding to the immunosuppressant FK506 under extremely alkaline conditions. Our proteomic analysis of V. anguillarum NB10 revealed that FklB (VaFklB) expression is significantly upregulated under extreme alkaline stress (pH 10). When the putative core promoter regions were coupled with a β-galactosidase reporter gene and introduced into Escherichia coli, we observed β-galactosidase activities of 61.47 ± 2.91 and 95.83 ± 6.76 Miller units (MU) at pH 9 and 10, respectively, after 4 h of stress exposure. These values represent 1.97- and 2.88-fold increases compared to normal conditions (25 °C, pH 7: 31.27 ± 1.15 MU). This alkaline-inducible promoter system has potential for biotechnological applications, including the development of pH-responsive gene expression systems, biomanufacturing processes requiring alkaline environments, and targeted activation of silent biosynthetic gene clusters for novel bioactive compound discovery. Our findings provide a valuable molecular tool for synthetic biology and metabolic engineering, enabling precise genetic control under specific environmental conditions that may revolutionize industrial biotechnology.
本研究介绍了鳗弧菌NB10启动子区域的鉴定与表征,该启动子可增强FK506结合蛋白(FKBP)型肽基脯氨酰顺/反异构酶(PPIase;FklB)的表达,FklB在极端碱性条件下能够结合免疫抑制剂FK506。我们对鳗弧菌NB10的蛋白质组分析表明,在极端碱性胁迫(pH 10)下,FklB(VaFklB)的表达显著上调。当将推定的核心启动子区域与β-半乳糖苷酶报告基因偶联并导入大肠杆菌后,在胁迫暴露4小时后,我们分别在pH 9和pH 10条件下观察到β-半乳糖苷酶活性为61.47±2.91和95.83±6.76米勒单位(MU)。与正常条件(25°C,pH 7:31.27±1.15 MU)相比,这些值分别增加了1.97倍和2.88倍。这种碱性诱导型启动子系统具有生物技术应用潜力,包括开发pH响应基因表达系统、需要碱性环境的生物制造过程以及为发现新型生物活性化合物而靶向激活沉默的生物合成基因簇。我们的研究结果为合成生物学和代谢工程提供了一种有价值的分子工具,能够在特定环境条件下实现精确的基因控制,这可能会彻底改变工业生物技术。