Biosynthesis of the dialkylmaleic anhydride-containing antibiotics, tautomycin and tautomycetin

Abstract

The biosynthetic origins of tautomycin and tautomycetin produced by Streptomyces spiroverticillatus and Streptomyces griseochromogenus, respectively, have been studied by feeding experiments with ¹³C labelled precursors. The left half of tautomycin and tautomycetin are synthesized from one propionate and a C-5 unit. The latter is formed from three acetate units with decarboxylation. The labelling pattern from ¹³C-acetates indicated that α-keto glutarate or an equivalent may be a precursor. The results of a feeding experiment of [1,2-¹³C₂]glutamate afforded the direct proof for this idea. The right half of tautomycin is biosynthesized by a polyketide pathway which starts with isobutyrate followed by introduction of a glycolate, five acetate and five propionate units. The terminal methyl carbon originates from an acetate-methyl probably formed by decarboxylation of the intermediate terminal β-keto carboxylate anion. The right half of tautomycetin is formed via a polyketide pathway which starts with acetate followed by introduction of three acetate and four propionate units and one butyrate unit.