Building a hybrid modular polyketide synthase to investigate ketosynthase selectivity

Polyketides are a diverse class of molecules which are biosynthesized in many different organisms, such as bacteria, fungi, plants, and animals. They are biologically active compounds and are often harnessed for pharmacological purposes. These natural products are synthesized by large enzyme complexes called polyketide synthases (PKSs), which are comprised of various domains, such as the acyltransferase (AT) and ketosynthase (KS), that each perform a specific chemical modification to build and process the polyketide. Type 1 modular PKSs in particular are organized into several modules, each containing different sets of domains, which act in an assembly line fashion to add extender units to a starter unit, shuttling the intermediates between the modules with the help of the acyl carrier protein (ACP). Upon reaching the final module, the product either cyclizes or dissociates for further processing (such as glycosylation).