Rational design of efficient modular cells.

Area of Science:

• Synthetic biology
• Metabolic engineering
• Biotechnology

Background:

• Microbial cell factories are crucial for biosynthesis.
• Developing efficient and versatile cell factories requires minimizing iterative strain optimization.
• Combinatorial biosynthesis of novel molecules demands adaptable chassis systems.

Purpose of the Study:

• To formulate a modular cell design principle for creating adaptable microbial cell factories.
• To develop a computational framework (MODCELL) for designing modular cells and exchangeable production modules.
• To enable efficient combinatorial biosynthesis of target molecules with minimal strain engineering.

Main Methods:

• Formulation of the modular cell design principle based on auxotrophy and metabolic pathway coupling.
• Development of the MODCELL framework utilizing metabolic pathway analysis.
• Identification of genetic modifications and coupling metrics for modular cell and production module design.
• Application to design modular *Escherichia coli* cells for alcohol and ester biosynthesis.

Main Results:

• Identification of three modular cells (MODCELL1, MODCELL2, MODCELL3) capable of coupling with specific production modules.
• Demonstration of MODCELL's step-by-step application for designing modular cell systems.
• Validation of MODCELL1 design for anaerobic production of ethanol, butanol, and ethyl butyrate using literature data.

Conclusions:

• The modular cell design principle and MODCELL framework facilitate the construction of versatile microbial cell factories.
• This plug-and-play approach significantly reduces iterative strain optimization for novel molecule biosynthesis.
• The developed modular cells and framework enable efficient combinatorial biosynthesis from various sugars under anaerobic conditions.