Traffic Control in Modular Polyketide Synthases

Polyketides and their derivatives offer a wide range of therapeutics in today’s pharmaceutical market, with annual sales reaching over 20 billion dollars.1 Key examples include antibiotics (erythromycin A), antifungals (amphotericin B), immunosuppressants (rapamycin), and anticancer agents (epothilone B). These chemically diverse and important products are made in biological systems by modular polyketide synthase (PKS) pathways. These megasynthases act as assembly lines, building the polyketide chain through consecutive condensation of coenzyme A-derived subunits.2 This month in ACS Central Science, Chaitan Khosla and co-workers provide insight on the mechanisms behind the impressive processivity demonstrated in the large multifunctional type 1 PKS assemblies.