The synthesis of polyketides, which involves the formation of a linear chain and its subsequent cyclization, is catalyzed by a set of enzymes known as polyketide synthases (PKSs). The PKSs control a number of variables in the linear chain synthesis: the number, identity, stereochemistry and order of the monomer units used in the different elongation reactions and the degree of reduction that occurs after each of these reactions. Changes in these variables lead to the formation of different polyketide linear chains and, consequently, a high diversity of polyketides. Although only 10,000 polyketide structures have been discovered so far, a theoretical analysis of the mechanism for the formation of the chain suggests that over a billion possible linear structures can be synthesized. The complexity in the number of possible structures led to the implementation of this system in BNICE, a computational framework that has been developed to study all possible biochemical pathways given a set of enzyme reaction rules. Consequently, the BNICE framework can be used to identify a library of all the possible polyketide structures and their corresponding synthetic pathways, which are then compared to the existing library of polyketides generated experimentally. Additionally, the theoretical production yield for the heterologous biosynthesis of these structures was evaluated using metabolic flux analysis and a genome-scale model of E. coli metabolism. Consequently, this formulation will prove useful in guiding experimental approaches to engineer the pathways for the synthesis of these novel polyketides.