Synthetic Strategy of Nonreducing Iterative Polyketide Synthases and the Origin of the Classical “Starter‐Unit Effect”

Getting started: The starter-unit effect in fungal polyketides stems from starter unit:acyl-carrier protein transacylase (SAT) domains found in nonreducing polyketide synthases (PKSs). Dissection of the PKSs involved in the production of naphthopyrone YWA1, tetrahydroxynaphthalene, cercosporin, and bikaverin revealed that their SAT domains had high selectivity for acetyl-CoA (see figure); this provides a biochemical rationale for this classically observed effect.