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Engineering microbial phenotypes through rewiring of genetic networks
Oliver P F Windram1, Rui T L Rodrigues1, Sangjin Lee1
1Centre for Synthetic Biology and Innovation and Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
Nucleic Acids Research
|April 4, 2017
Summary
Synthetic biology can program cellular behavior. Rewiring yeast
Area of Science:
- Synthetic biology
- Metabolic engineering
- Systems biology
Background:
- Cellular behavior programming is key for synthetic biology applications.
- Interactions between engineered and host cell networks impact functionality.
- Orthogonal systems are challenged by endogenous network interference.
Purpose of the Study:
- To develop a strategy for rewiring endogenous yeast regulatory networks.
- To enhance compatibility with synthetic protein and metabolite production.
- To improve heterologous protein expression and metabolite titers.
Main Methods:
- Rewiring endogenous cellular regulatory networks in yeast.
- Introducing novel connections within the transcriptional network.
- Selection for specific phenotypes and analysis of library members.
- Assessing topological features like betweenness centrality.
Main Results:
- Novel network connections increased heterologous protein and metabolite production.
- Yeast strains showed enhanced protein expression and terpenoid production.
- Transcriptional regulation between signaling and nitrogen pathways improved protein production.
- High betweenness centrality was identified as a key topological feature.
Conclusions:
- Rewiring endogenous networks enhances synthetic biology compatibility.
- This strategy improves heterologous protein and metabolite yields.
- Topological analysis aids in understanding engineered network performance.
- This approach is a powerful tool for engineering cellular behavior.