Biosynthesis of the antitumor antibiotic sparsomycin

The biosynthesis of the antitumor antibiotic sparsomycin (1) has been investigated by administration of isotopically labeled precursors to Streptomyces sparsogenes var. sparsogenes. These studies indicated that the dithioacetal moiety (2) of sparsomycin is derived from L-cysteine via the intermediacy of S-methylcysteine and S-(methylthiomethyl)cysteine, with reduction of the carboxyl group of S-(methylthiomethyl)cysteine preceding attachment of the uracil moiety (3). Investigations of the origin of the uracil moiety (3) of sparsomycin revealed that it is derived from L-tryptophan by a process that involves loss of the side chain and oxidative ring opening of both rings of the amino acid. The intermediacy of N-formylanthranilic acid in this process was ruled out. investigations of the terminal stage in the biosyntbesis of the uracil moiety (3) demonstrated that it resembles the conversion of inosine-5'-monophosphate into xanthosine-5'-monophosphate.