(A) Examples of type II polyketides with the starter units shown in blue. (B) DpsC catalyzes the transfer of small acyl-CoAs, including propionyl-CoA, to the acyl carrier protein (ACP) and also the initial chain elongation reaction that condenses the propionyl starter unit with malonyl-ACP to afford the growing intermediate. Eight more rounds of chain elongation produce the unstable, linear poly-β-ketone intermediate that is cyclized and tailored to become daunorubicin. (C) Oxetanes are isosteres for the carbonyl group. (D) Probe 1, with the thioester carbonyl group replaced by an oxetane, mimics malonyl-PPT.