Spatiotemporal Gene Expression by a Genetic Circuit for Chemical Production in Escherichia coli .
Bo ZhangHui YangZidan WuJiayuan PanShirong LiLifeng ChenXue CaiZhi-Qiang LiuYu-Guo ZhengPublished in: ACS synthetic biology (2023)
Gene expression in spatiotemporal distribution improves the ability of cells to respond to changing environments. For microbial cell factories in artificial environments, reconstruction of the target compound's biosynthetic pathway in a new spatiotemporal dimension/scale promotes the production of chemicals. Here, a genetic circuit based on the Esa quorum sensing and lac operon was designed to achieve the dynamic temporal gene expression. Meanwhile, the pathway was regulated by an l-cysteine-specific sensor and relocalized to the plasma membrane for further flux enhancement to l-cysteine and toxicity reduction on a spatial scale. Finally, the integrated spatiotemporal regulation circuit for l-cysteine biosynthesis enabled a 14.16 g/L l-cysteine yield in Escherichia coli . Furthermore, this spatiotemporal regulation circuit was also applied in our previously constructed engineered strain for pantothenic acid, methionine, homoserine, and 2-aminobutyric acid production, and the titer increased by 29, 33, 28, and 41%, respectively. These results highlighted the applicability of our spatiotemporal regulation circuit to enhance the performance of microbial cell factories.
Keyphrases
- gene expression
- escherichia coli
- dna methylation
- fluorescent probe
- single cell
- living cells
- microbial community
- genome wide
- induced apoptosis
- stem cells
- oxidative stress
- cell cycle arrest
- klebsiella pneumoniae
- copy number
- pseudomonas aeruginosa
- mesenchymal stem cells
- cell proliferation
- endoplasmic reticulum stress
- amino acid
- single molecule