BPKS from Botrytis cinerea is a novel type III polyketide synthase that accepts C4–C18 aliphatic acyl-CoAs and benzoyl-CoA as the starters to form pyrones, resorcylic acids and resorcinols through sequential condensation with malonyl-CoA. The catalytic efficiency (kcat/Km) of BPKS was 2.8 × 105 s−1 M−1 for palmitoyl-CoA, the highest ever reported. Substrate docking analyses addressed the unique features of BPKS such as its high activity and high specificity toward long chain acyl-CoAs.