Polyketide synthases are multifunctional enzymes that catalyze the biosynthesis of polyketides. These enzymes make attractive targets because they can be modified to produce commodity chemicals. The invention herein describes methods for producing polyketide synthase variants whose activity and/or substrate specificity can be tailored. An example of a polyketide synthase variant would be 2-pyrone synthase, which produces 2-pyrone. Other modified synthase variants can be generated to produce other key materials including ketides, lactones, etc.