Light-induced programmable solid-liquid phase transition of biomolecular condensates for improved biosynthesis.
Ke Jin, Wenwen Yu, Yanfeng Liu, Jianghua Li, Guocheng Du, Jian Chen, Long Liu, Xueqin Lv
Author Information
Ke Jin: 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.
Wenwen Yu: 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.
Yanfeng Liu: 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.
Jianghua Li: 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.
Guocheng Du: Science Center for Future Foods, Jiangnan University, Wuxi 214122, China.
Jian Chen: Science Center for Future Foods, Jiangnan University, Wuxi 214122, China.
Long Liu: 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.
Xueqin Lv: 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. Electronic address: lvxueqin@jiangnan.edu.cn.
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.
