Developing a pathway-independent and full-autonomous global resource allocation strategy to dynamically switching phenotypic states
Junjun Wu, Meijiao Bao, Xuguo Duan, Peng Zhou, Caiwen Chen, Jiahua Gao, Shiyao Cheng, Qianqian Zhuang, Zhijun Zhao
Abstract
A grand challenge of biological chemical production is the competition between synthetic circuits and host genes for limited cellular resources. Quorum sensing (QS)-based dynamic pathway regulations provide a pathway-independent way to rebalance metabolic flux over the course of the fermentation. Most cases, however, these pathway-independent strategies only have capacity for a single QS circuit functional in one cell. Furthermore, current dynamic regulations mainly provide localized control of metabolic flux. Here, with the aid of engineering synthetic orthogonal quorum-related circuits and global mRNA decay, we report a pathway-independent dynamic resource allocation strategy, which allows us to independently controlling two different phenotypic states to globally redistribute cellular resources toward synthetic circuits. The strategy which could pathway-independently and globally self-regulate two desired cell phenotypes including growth and production phenotypes could totally eliminate the need for human supervision of the entire fermentation.