4.7 Review

Multilayer Genetic Circuits for Dynamic Regulation of Metabolic Pathways

Journal

ACS SYNTHETIC BIOLOGY
Volume 10, Issue 7, Pages 1587-1597

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00073

Keywords

dynamic regulation; logic gate; multilayer gene circuits; pathway engineering; synthetic biology

Funding

  1. Key Research and Development Program of China [2020YFA0908300, 2018YFA0900300]
  2. National Natural Science Foundation of China [32070085, 31871784, 31870085, 32021005]
  3. Fundamental Research Funds for the Central Universities [JUSRP52019A]
  4. Shandong Province Key R&D Program (Major Science and Technology Innovation Project) [2019JZZY011002]

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Dynamic regulation of metabolic pathways involves complex genetic circuits to process various signals and control metabolic flux for optimal synthesis of target molecules.
The dynamic regulation of metabolic pathways is based on changes in external signals and endogenous changes in gene expression levels and has extensive applications in the field of synthetic biology and metabolic engineering. However, achieving dynamic control is not trivial, and dynamic control is difficult to obtain using simple, single-level, control strategies because they are often affected by native regulatory networks. Therefore, synthetic biologists usually apply the concept of logic gates to build more complex and multilayer genetic circuits that can process various signals and direct the metabolic flux toward the synthesis of the molecules of interest. In this review, we first summarize the applications of dynamic regulatory systems and genetic circuits and then discuss how to design multilayer genetic circuits to achieve the optimal control of metabolic fluxes in living cells.

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