Metabolic engineers must precisely regulate the expression of multiple genes to optimize the productivity of the cell. Excessive expression of any gene can be toxic to the engineered cell, and could therefore reduce yield. e expression of multiple genes encoding the enzymes of a metabolic pathway must be coordinated in order to avoid bottlenecks.1,2 is “ne tuning” problem is complicated by the context-dependence of complex molecular systems. All biological systems are complex, which means that interactions between their components create emergent properties. A promoter that produces moderate steady-state concentrations of one transcript may produce too much or too little of another. A chromosomal promoter that is tightly repressed can be leaky when cloned into a high copy number plasmid. A protein that is essential to one cell type can be toxic to another.