TY - JOUR
T1 - Programmable biomolecular switches for rewiring flux in Escherichia coli
AU - Gao, Cong
AU - Hou, Jianshen
AU - Xu, Peng
AU - Guo, Liang
AU - Chen, Xiulai
AU - Hu, Guipeng
AU - Ye, Chao
AU - Edwards, Harley
AU - Chen, Jian
AU - Chen, Wei
AU - Liu, Liming
N1 - Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Synthetic biology aims to develop programmable tools to perform complex functions such as redistributing metabolic flux in industrial microorganisms. However, development of protein-level circuits is limited by availability of designable, orthogonal, and composable tools. Here, with the aid of engineered viral proteases and proteolytic signals, we build two sets of controllable protein units, which can be rationally configured to three tools. Using a protease-based dynamic regulation circuit to fine-tune metabolic flow, we achieve 12.63 g L−1 shikimate titer in minimal medium without inducer. In addition, the carbon catabolite repression is alleviated by protease-based inverter-mediated flux redistribution under multiple carbon sources. By coordinating reaction rate using a protease-based oscillator in E. coli, we achieve d-xylonate productivity of 7.12 g L−1 h−1 with a titer of 199.44 g L−1. These results highlight the applicability of programmable protein switches to metabolic engineering for valuable chemicals production.
AB - Synthetic biology aims to develop programmable tools to perform complex functions such as redistributing metabolic flux in industrial microorganisms. However, development of protein-level circuits is limited by availability of designable, orthogonal, and composable tools. Here, with the aid of engineered viral proteases and proteolytic signals, we build two sets of controllable protein units, which can be rationally configured to three tools. Using a protease-based dynamic regulation circuit to fine-tune metabolic flow, we achieve 12.63 g L−1 shikimate titer in minimal medium without inducer. In addition, the carbon catabolite repression is alleviated by protease-based inverter-mediated flux redistribution under multiple carbon sources. By coordinating reaction rate using a protease-based oscillator in E. coli, we achieve d-xylonate productivity of 7.12 g L−1 h−1 with a titer of 199.44 g L−1. These results highlight the applicability of programmable protein switches to metabolic engineering for valuable chemicals production.
UR - http://www.scopus.com/inward/record.url?scp=85071080222&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-11793-7
DO - 10.1038/s41467-019-11793-7
M3 - 文章
C2 - 31434894
AN - SCOPUS:85071080222
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3751
ER -