Polyketides are an interesting class of secondary metabolites produced by polyketide synthases (PKS) in a step-wise fashion of chain extension follwed by possible methylation, keto-reduction, dehydration and enoyl reduction. Iterative polyketide synthase (iPKS) consist of a single module containing one copy of each catalytic domain. During each round of chain extension the domains can be switched on and off in a process known as programming. The programming of iPKS is not understood. This project is aimed at increasing the understanding the programming of iPKS. Squalestatin tetraketide synthase (SQTKS) has been taken as a model due its simplicity compared to other PKS systems. Work in the group has afforded soluble catalytic active isolated domains. These domains are currently being assayed with a range of synthetic compounds which mimic natural PKS substrates. The substrates are designed to probe for structural features which control the programing of the isolated domains.