Doug Roberts (2010-2014)
Iterative polyketide synthase (iPKS) differ considerably to modular polyketide synthase (mPKS). mPKS comprise of many modules that contain all the domains required for each round of chain extension whereas iPKS only have a single module and so only has a single copy of each domain. In every round of chain extension the domains can be switched on and off in a mechanism known as programming. The programming of iPKS is not fully understood and this project is aimed at understanding the mechanism that controls programming.
To investigate programming in iPKS, squalestatin tetraketide synthase (SQTKS) was used as a model system. By comparing the genetic sequence with other know enzymes, soluble catalytically-active domains were produced. These were designed firstly to test if an isolated domain can exhibit the same degree of programming as the entire PKS. The isolated domains were assayed with a range of compounds that mimic the biosynthesis of polyketides and the rates were compared to establish what structural features control the programming of the isolated domain.