Biosynthesis of monensins and 3-O-demethylmonensins inStreptomyces cinnamonensisin the presence of methylation inhibitors

Abstract

We studied the effect of inhibitors of methylation (p‐aminosalicylic acid, sulfonamides, aminopterine) on the biosynthesis of the oligoketide antibiotics, monensins A and B, and their cometabolites, 3‐O‐demethylmonensins A and B. The inhibitors were supplied to the culture medium of Streptomyces cinnamonensis LO‐63 at the beginning or in the 17th hour of cultivation. Under noninhibitory conditions 3‐O‐demethylmonensins represent 2% total monensins at the most. The highest relative yield of demethylated monensins was achieved with aminopterine (2.3 · 10−2 mM) added in the 17th hour. A high proportion of 3‐O‐demethylated monensins, 28–30% of the total production, was brought about by sulfadimidine and sulfathiazole (20 mM); however, the agents also caused a substantial inhibition of the overall production. Sulfaguanidine and phthalylsulfathiazole were poor inhibitors of methylation, sulfisoxazole and p‐aminosalicylic acid had no effect. The strong effect of aminopterine on the biosynthesis of 3‐O‐demethylmonensins was confirmed in the regulatory mutant S. cinnamonensis ACB‐ABR‐2 which produces mainly monensin A.