Biosynthesis of monensins and 3-O-demethylmonensins in Streptomyces cinnamonensis in the presence of methylation inhibitors

Add time:07/16/2019    Source:sciencedirect.com

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.

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