Some applications of metabolic engineering, particularly those in which a high rate of conversion of substrate to product is needed, require control of flux through the central carbon metabolic pathway. This can be problematic, because it requires increased activity of many enzymes in the pathway, and regulation of the pathway is rigid. On page 1283, Ostergaard et al. apply a strategy to uniformly increase the enzyme activities through the yeast GAL pathway by engineering the regulatory networks for gene expression—reducing the levels of negative regulators and increasing levels of positive activators. In this case, by eliminating three known negative regulators of the GAL pathway, Gal6, Gal80, and Mig1, they could increase flux through the galactose utilization pathway by 41%.