Biosynthesis of Streptomycin

Abstract

Abstract scyllo-Inositol was shown to be a precursor of the streptidine moiety of streptomycin. Addition of scyllo-inositol-2-3H to cultures of Streptomyces griseus resulted in a 7.1 to 7.8% incorporation of tritium into the streptomycin synthesized by the organism. All of the incorporated tritium was found in the streptidine portion of the molecule. Evidence is presented that S. griseus synthesizes myo-inositol from d-glucose and that the organism interconverts myo-inositol and scyllo-inositol. The implications of these findings are discussed. The biosynthesis of the N-methyl-l-glucosamine moiety of streptomycin from d-glucose, l-glucose, and d-glucosamine by S. griseus has been studied. d-Glucoses, labeled with 14C in positions 1,2, 3–4, or 6, were given to cultures of S. griseus. The distributions of label found in the N-methyl-l-glucosamine moiety of the streptomycin synthesized further support a mechanism involving multiple inversion of the asymmetrical carbon atoms of d-glucose to from the l-sugar. l-Glucose-1-14C was administered to S. griseus. No incorporation of isotope into streptomycin was detected. Evidence was also obtained that d-glucosamine plays a role in the synthesis of N-methyl-l-glucosamine. Administration of d-glucosamine-1-14C to cultures resulted in greater percentage incorporation of isotopic carbon into the N-methyl-l-glucosamine moiety of the antibiotic than seen with d-glucose-1-14C under similar conditions. Degradation studies disclosed that the major concentration of incorporated label was in carbon 1 of the N-methyl-l-glucosamine moiety.