This thesis reports studies on the substrate specificity of crucial ketosynthase (KS) domains from trans-AT Polyketide Synthases (PKSs). Using a combination of electrospray ionisation-mass spectrometry (ESI-MS) and simple N-acetyl cysteamine (SNAC) substrate mimics, the specificity of a range of KS domains from the bacillaene and psymberin PKSs have been succsessfully studied with regard to the initial acylation step of KS-catalysis.

In addition, the ability to alter the substrate tolerance of KS domains by simple point mutations in the active site has been demonstrated. A series of...