Systems approaches for optimizing CO₂ fixation pathways

Area of Science:

• Synthetic biology
• Metabolic engineering
• Systems biology

Background:

• Designing and implementing carbon dioxide (CO2) fixation pathways is crucial for biotechnological applications.
• A significant gap exists between theoretical pathway design and achieving productive microbial strains.

Purpose of the Study:

• To survey recent advancements in CO2 fixation pathway design and implementation.
• To identify challenges and propose solutions for bridging the gap between pathway design and strain productivity.

Main Methods:

• Review of recent literature on CO2 fixation pathway engineering.
• Application of systems biology tools including kinetic modeling, retrobiosynthesis, quantitative proteomics, and adaptive laboratory evolution.

Main Results:

• Pathway design often overlooks hidden factors like enzyme energy demands and regulatory network adaptations.
• Systems biology tools aid in evaluating pathway dynamics, stability, host adaptation, and metabolite interference.
• Adaptive laboratory evolution is effective for optimization but requires growth-linked phenotypes; post-evolution analysis shows significant proteome reallocation for pathway integration.

Conclusions:

• Overcoming the design-to-productivity gap requires accounting for complex biological interactions and host responses.
• Systems biology approaches are essential for rational design and optimization of microbial CO2 fixation pathways.
• Further research integrating computational tools and experimental evolution is needed for robust CO2-fixing strains.