Jin Ke, Yu Wenwen, Liu Yanfeng, Li Jianghua, Du Guocheng, Chen Jian, Liu Long, Lv Xueqin
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, Jiangnan University, Wuxi 214122, China; Science Center for Future Foods, Jiangnan University, Wuxi 214122, China.
Science Center for Future Foods, Jiangnan University, Wuxi 214122, China.
Trends Biotechnol. 2025 Jun;43(6):1403-1424. doi: 10.1016/j.tibtech.2025.02.012. Epub 2025 Mar 12.
Keeping condensates in liquid-like states throughout the biosynthesis process in microbial cell factories remains an ongoing challenge. Here, we present a light-controlled phase regulator, which maintains the liquid-like features of synthetic condensates on demand throughout the biosynthesis process upon light induction, as demonstrated by various live cell-imaging techniques. Specifically, the tobacco etch virus (TEV) protease controlled by light cleaves intrinsically disordered proteins (IDPs) to alter their valency and concentration for controlled phase transition and programmable fluidity of cellular condensates. As a proof of concept, we harness this capability to significantly improve the production of squalene and ursolic acid (UA) in engineered Saccharomyces cerevisiae. Our work provides a powerful approach to program the solid-liquid phase transition of biomolecular condensates for improved biosynthesis.
在微生物细胞工厂的整个生物合成过程中，使凝聚物保持类液态仍然是一个持续存在的挑战。在此，我们展示了一种光控相调节器，通过各种活细胞成像技术证明，在光诱导下，它能在整个生物合成过程中按需维持合成凝聚物的类液态特征。具体而言，受光控制的烟草蚀纹病毒（TEV）蛋白酶切割内在无序蛋白（IDP），以改变其化合价和浓度，从而实现细胞凝聚物的可控相变和可编程流动性。作为概念验证，我们利用这一能力显著提高了工程酿酒酵母中角鲨烯和熊果酸（UA）的产量。我们的工作为调控生物分子凝聚物的固 - 液相转变以改善生物合成提供了一种强大的方法。
