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Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli.

Publication ,  Journal Article
Ye, Z; Li, S; Hennigan, JN; Lebeau, J; Moreb, EA; Wolf, J; Lynch, MD
Published in: Metabolic engineering
November 2021

We report that two-stage dynamic control improves bioprocess robustness as a result of the dynamic deregulation of central metabolism. Dynamic control is implemented during stationary phase using combinations of CRISPR interference and controlled proteolysis to reduce levels of central metabolic enzymes. Reducing the levels of key enzymes alters metabolite pools resulting in deregulation of the metabolic network. Deregulated networks are less sensitive to environmental conditions improving process robustness. Process robustness in turn leads to predictable scalability, minimizing the need for traditional process optimization. We validate process robustness and scalability of strains and bioprocesses synthesizing the important industrial chemicals alanine, citramalate and xylitol. Predictive high throughput approaches that translate to larger scales are critical for metabolic engineering programs to truly take advantage of the rapidly increasing throughput and decreasing costs of synthetic biology.

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Published In

Metabolic engineering

DOI

EISSN

1096-7184

ISSN

1096-7176

Publication Date

November 2021

Volume

68

Start / End Page

106 / 118

Related Subject Headings

  • Synthetic Biology
  • Metabolic Networks and Pathways
  • Metabolic Engineering
  • Escherichia coli
  • Biotechnology
  • 3106 Industrial biotechnology
  • 3101 Biochemistry and cell biology
  • 1003 Industrial Biotechnology
 

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Ye, Z., Li, S., Hennigan, J. N., Lebeau, J., Moreb, E. A., Wolf, J., & Lynch, M. D. (2021). Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli. Metabolic Engineering, 68, 106–118. https://doi.org/10.1016/j.ymben.2021.09.009
Ye, Zhixia, Shuai Li, Jennifer N. Hennigan, Juliana Lebeau, Eirik A. Moreb, Jacob Wolf, and Michael D. Lynch. “Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli.Metabolic Engineering 68 (November 2021): 106–18. https://doi.org/10.1016/j.ymben.2021.09.009.
Ye Z, Li S, Hennigan JN, Lebeau J, Moreb EA, Wolf J, et al. Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli. Metabolic engineering. 2021 Nov;68:106–18.
Ye, Zhixia, et al. “Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli.Metabolic Engineering, vol. 68, Nov. 2021, pp. 106–18. Epmc, doi:10.1016/j.ymben.2021.09.009.
Ye Z, Li S, Hennigan JN, Lebeau J, Moreb EA, Wolf J, Lynch MD. Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli. Metabolic engineering. 2021 Nov;68:106–118.
Journal cover image

Published In

Metabolic engineering

DOI

EISSN

1096-7184

ISSN

1096-7176

Publication Date

November 2021

Volume

68

Start / End Page

106 / 118

Related Subject Headings

  • Synthetic Biology
  • Metabolic Networks and Pathways
  • Metabolic Engineering
  • Escherichia coli
  • Biotechnology
  • 3106 Industrial biotechnology
  • 3101 Biochemistry and cell biology
  • 1003 Industrial Biotechnology