The avermectin initial aglycon is further modified by other enzymes in the avermectin biosynthetic gene cluster. AveE has cytochrome P450 monooxygenase activity and facilitates the furan ring formation between C6 and C8. AveF has NAD(P)H-dependent ketoreductase activity which reduces the C5 keto group to a hydroxyl. AveC influences the dehydratase activity in module two (affecting C22-C23), although the mechanism by which it does this is not clear. AveD has SAM-dependent C5 O-methyltransferase activity. Whether AveC or AveD acts on the aglycon determines whether the resulting avermectin aglycon will produce avermectin , respectively.