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.
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000871:Anthelmintics / Q000302:isolation & purification* / Q000494:pharmacology; D007306:Insecticides / Q000302:isolation & purification* / Q000494:pharmacology; D007559:Ivermectin / Q000031:analogs & derivatives*; D007783:Lactones / Q000096:biosynthesis / Q000302:isolation & purification* / Q000494:pharmacology; D008780:Methyltransferases / Q000032:analysis; D013302:Streptomyces / Q000378:metabolism*
D000871:Anthelmintics; D007306:Insecticides; D007783:Lactones; C047538:demethylavermectins; D007559:Ivermectin; C019264:avermectin; D008780:Methyltransferases; D000241:Adenosine; C006235:sinefungin