Huang Cheng, Zhao Jie, Tan Zichun, Dai Shang, Wang Binqiang, Xie Zhenming, Zhang Furong, Zhou Yulong, Yu Ning, Cai Chunhui, Yao Yonghua, Wang Baojun, Tian Bing
Institute of Biophysics, College of Life Sciences, Zhejiang University, Hangzhou, China.
College of Life Sciences, Nanjing Agricultural University, Nanjing, China.
Sci Adv. 2025 Aug 29;11(35):eadv7892. doi: 10.1126/sciadv.adv7892. Epub 2025 Aug 27.
Current gene circuits designed to time gene expression depend on the intricate interactions among various regulators and their targets, which confines them to a limited range of temporal tunability. Here, we report a programmable timer switch of gene expression termed BioFuse, which allows the reaction time ranging from hours to days. BioFuse comprises a series of fuse-like tandem DNA cassettes that can be sequentially edited by the adenine base editors (ABEs), resulting in either the activation or deactivation of a downstream gene once the editing is complete. Adjusting the number of DNA cassettes incorporated allows precise programming of BioFuse's reaction time. Applying BioFuse to control carotenoid biosynthesis genes decouples lycopene production from growth in and increases lycopene yield without external inducers. Using BioFuse in a bacterial autolysis system enables timely and efficient protein release. BioFuse offers a versatile tool for precise, wide-range timing of gene expression and metabolic activities in bacteria, with potential applications in industry and biomedicine.
目前设计用于定时基因表达的基因回路依赖于各种调节因子及其靶标之间复杂的相互作用,这将它们限制在有限的时间可调范围内。在此,我们报告了一种称为BioFuse的可编程基因表达定时器开关,其反应时间范围从数小时到数天。BioFuse由一系列类似保险丝的串联DNA盒组成,这些DNA盒可以由腺嘌呤碱基编辑器(ABE)进行顺序编辑,一旦编辑完成,就会导致下游基因的激活或失活。调整所包含的DNA盒数量可以精确编程BioFuse的反应时间。将BioFuse应用于控制类胡萝卜素生物合成基因,可使番茄红素的产生与生长脱钩,并在无外部诱导剂的情况下提高番茄红素产量。在细菌自溶系统中使用BioFuse能够及时、高效地释放蛋白质。BioFuse为细菌中基因表达和代谢活动的精确、广泛定时提供了一种通用工具,在工业和生物医学领域具有潜在应用价值。