Lomaiviticin biosynthesis is thought to utilize a propionyl starter unit for a type II polyketide synthase (PKS). Discovery of the lomaiviticin (lom) biosynthetic gene cluster suggested an unusual method for starter unit generation involving a bifunctional acyltransferase/decarboxylase (AT/DC) thus far observed only in type I PKS pathways. In vitro biochemical characterization of AT/DC Lom62 confirmed its ability to generate a propionyl-acyl carrier protein (ACP), revealing a new role for this enzymatic activity within natural product biosynthesis.