Model for 6,8a-seco-6,8a-deoxy-5-oxoavermectin aglycon formation and predicted domain structure of the avermectin PKS. Each circle represents an enzymatic domain in the PKS multifunctional polypeptide. AT, acyltransferase; DH, dehydratase; KR, β-ketoacyl-ACP reductase; KS, β-ketoacyl-ACP synthase; TE, thioesterase. The reaction order from module 7 to 9 and from 10 to 12 in aveA3 and aveA4, respectively, is drawn in the direction opposite to the gene order on the genome. The crossed-out domain in module 7 is nonfunctional. The shaded domain in module 10 does not function in polyketide-chain elongation.