Demethylavermectins. Biosynthesis, isolation and characterization

Streptomyces avermitilis normally produces eight avermectins. Avermectin A components contain three methoxyl groups; two on the oleandrose disaccharide and one on the aglycone moiety at C5. Avermectin B components contain methoxyl groups only on the oleandrose disaccharide. Sinefungin inhibits methylation at all three sites. Addition of sinefungin to S. avermitilis Agly-1, a mutant which produces virtually only avermectin aglycone A components, alters the fermentation and causes an accumulation of avermectin aglycone B components. Addition of sinefungin to S. avermitilis 08, a high producing strain, results in accumulation of 8 new avermectins which lack methoxyl groups on the oleandrose moieties as well as the aglycone. These new avermectins were isolated and shown to possess anthelmintic and insecticidal activity.