Streptomycin Biosynthesis and Metabolism

Extracts of streptomycin-producing strains of Sfreptomyces phosphorylate dihydrostreptomycin (sfrepfidino)phosphate with adenosine 5’-triphosphate as the phosphoryl donor. The second phosphate is esterified with the dihydrostreptobiosamine moiety. Streptomycin (sfreptidino)phosphate was not phosphorylated under similar conditions. Because of its lability, the new enzyme that is responsible for the phosphorylation could not be separated from the previously described streptomycin streptidinokinase, present in streptomycin producers, which phosphorylates the streptidine moieties of both streptomycin and dihydrostreptomycin. However, extracts of a strain which lacks streptidinokinase, Streptomyces griseus ATCC 10971, phosphorylated the dihydrostreptobiosamine moieties of both dihydrostreptomycin and dihydrostreptomycin (sfreptidino)phosphate; streptomycin was not phosphorylated. The kinase is an idiophase enzyme, not detectable during the early rapid growth phase of these Streptomyces. The observation that streptomycin(sfreptidino)phosphate was phosphorylated only after reduction with borohydride to the dihydrostreptomycin derivative suggests that the second phosphate is esterified with the 3hydroxymethyl group of the dihydrostreptose moiety of dihydrostreptomycin(sfrepfidino)phosphate. Fresh extracts of streptomycin producers can synthesize the diphosphorylated derivative of dihydrostreptomycin from dihydrostreptomycin via either of the two monophosphorylated dihydrostreptomycin derivatives.