Screening for new antifolates of microbial origin and a new antifolate AM-8402.

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Abstract
A screening method was established for new specific inhibitors of folate metabolism. Culture broths of soil isolates were selected based on relative microbial activity. A culture, to be retained, must be active against Enterococcus faecium grown in a medium which contains a limited amount of pteroic acid but lacks activity against the microorganism grown in a medium supplemented with thymidine. By this screening method, three new antibiotics, diazaquinomycins A and B and AM-8402 were selected from eight thousand soil isolates. The isolation and structures of diazaquinomycins have been reported. AM-8402 is a new antifolate active against Gram-positive bacteria and mycoplasmas. It consists of a nanaomycin D moiety as chromophore and a deoxysugar and is structurally related to medermycin.