Rewiring carbon flux in Escherichia coli using a bifunctional molecular switch
Journal article, 2020

The unbalanced distribution of carbon flux in microbial cell factories can lead to inefficient production and poor cell growth. Uncoupling cell growth and chemical synthesis can therefore improve microbial cell factory efficiency. Such uncoupling, which requires precise manipulation of carbon fluxes, can be achieved by up-regulating or down-regulating the expression of enzymes of various pathways. In this study, a dynamic turn-off switch (dTFS) and a dynamic turn-on switch (dTNS) were constructed using growth phase-dependent promoters and degrons. By combining the dTFS and dTNS, a bifunctional molecular switch that could orthogonally regulate two target proteins was introduced. This bifunctional molecular switch was used to uncouple cell growth from shikimic acid and D-glucaric acid synthesis, resulting in the production of 14.33 g/L shikimic acid and the highest reported productivity of D-glucaric acid (0.0325 g/L/h) in Escherichia coli MG1655. This proved that the bifunctional molecular switch could rewire carbon fluxes by controlling target protein abundance.

Metabolic engineering

Dynamic regulation

Synthetic biology

Metabolic flux regulation

Author

Jianshen Hou

Jiangnan University

Cong Gao

Jiangnan University

Liang Guo

Jiangnan University

Jens B Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Qiang Ding

Jiangnan University

Wenxiu Tang

Jiangnan University

Guipeng Hu

Jiangnan University

Xiulai Chen

Jiangnan University

Liming Liu

Jiangnan University

Metabolic Engineering

1096-7176 (ISSN) 1096-7184 (eISSN)

Vol. 61 47-57

Subject Categories

Cell Biology

Biochemistry and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1016/j.ymben.2020.05.004

More information

Latest update

6/5/2020 6