Energy Aware Technology Mapping of Genetic Logic Circuits.

Area of Science:

• Synthetic Biology
• Systems Biology
• Bioengineering

Background:

• Energy dissipation is crucial for all living systems, including cellular functions.
• Genetic circuits can impose an energy burden, impairing cell survival and circuit functionality.
• Existing genetic design automation (GDA) software lacks non-equilibrium models for energy dissipation and response curves.

Purpose of the Study:

• Introduce Energy Aware Technology Mapping (EATM) for automated genetic logic circuit design.
• Optimize circuits for both energy efficiency and functional performance.
• Incorporate non-equilibrium thermodynamics into GDA software.

Main Methods:

• Developed an energy-aware non-equilibrium steady state (NESS) model for gene expression.
• Modeled energy dissipation (linked to entropy production rate) and transcriptional bursting.
• Evaluated EATM against functionally optimized circuits using benchmark genetic logic circuits.

Main Results:

• Functional performance and energy efficiency are often disjoint optimization goals for genetic circuits.
• EATM improved energy efficiency by an average of 37.2% compared to functionally optimized variants.
• EATM enables designing circuits with the energy efficiency of circuits that are one to two gates smaller, with structural variants offering further improvements.

Conclusions:

• Energy Aware Technology Mapping enables energy efficiency by design in genetic logic circuits.
• This approach extends current GDA tools and complements methods for managing cellular burden *in vivo*.
• Incorporating energy demand into the design process is key for developing robust and efficient synthetic biological systems.