Synthetic biosensor accelerates evolution by rewiring carbon metabolism toward a specific metabolite

Area of Science:

• Biotechnology
• Metabolic Engineering
• Synthetic Biology

Background:

• Efficient biochemical production requires balancing carbon flux between cell growth and product formation.
• Improper flux distribution can inhibit growth and reduce product yield.

Purpose of the Study:

• To develop a method for optimizing cellular resource allocation for enhanced biochemical production.
• To investigate the genetic basis of improved metabolic flux control.

Main Methods:

• Utilized a synthetic biosensor to link metabolite production with cell growth.
• Employed adaptive laboratory evolution (ALE) under selective pressure.
• Analyzed mutations in global transcriptional regulators in *Escherichia coli*.

Main Results:

• Identified mutations in conserved protein regions that alter gene expression in central carbon metabolism.
• Rewired carbon flux towards 3-hydroxypropionic acid (3-HP) production from glycerol.
• Increased 3-HP yield and reduced acetate byproduct formation by mitigating overflow metabolism.

Conclusions:

• Synthetic biosensors coupled with ALE are effective for optimizing metabolic pathways.
• Mutations in global regulators can precisely reallocate cellular resources for improved production.
• This approach enhances the yield of target compounds like 3-HP.