Two-stage dynamic deregulation of metabolism improves process robustness & scalability in engineered E. coli.
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.
Duke Scholars
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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
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Start / End Page
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