Insights into docking in megasynthases from the investigation of the toblerol trans-AT polyketide synthase: many α-helical means to an end†

Abstract The fidelity of biosynthesis by modular polyketide synthases (PKSs) depends on specific moderate affinity interactions between successive polypeptide subunits mediated by docking domains (DDs). These sequence elements are notably portable, allowing their transplantation into alternative biosynthetic and metabolic contexts. Herein, we use integrative structural biology to characterize a pair of DDs from the toblerol trans-AT PKS. Both are intrinsically disordered regions (IDRs) that fold into a 3 α-helix docking complex of unprecedented topology. The C-terminal docking domain (CDD) resembles