1. Problem We Address: Generalizeable Strategies for Improving Flux of Engineered Metabolic Pathways

2. Motivation #1: Pathways removed from natural regulation when heterologously expressed

3. Motivation #2: Differing levels of activity of pathway enzymes

4. Motivation #3: Complex Enzyme Structures Makes Direct Enzyme Optimization Difficult and Case-dependent

5. Our Strategy: Employ Natural Machinery for Targeted Pathway Regulation

6. Enzymes Have Different Levels of Activity (Turnover Fluxes)

7. Synthetic Scaffolds Can Co-localize Pathway Enzymes and Reduce Intermediate Runoff

8. Synthetic Scaffolds Can be Designed to Optimize Flux through the Pathway via Control of Relative Enzyme Ratios

9. Summary: Addition of Modularity To Nonmodular Metabolic Pathway
Control over Pathway flux
Through:
1. Corecruitment
2. Relative enzyme
ratios

10. Synthetic Scaffolds Have Dramatic Effect On Model System (Mevalonate Pathway)

11. Modular Strategies are Scalable

12. Synopsis
Modular parts (domain/ligands, enzymes) used to construct synthetic scaffolds are well-characterized.
We are interested in how these parts can be used to build sophisticated machines and probing the engineering principles by which these machines can be programmed.
Can predictive models be made based on simple equilibrium theory?