Last step in the biosynthesis of streptomycin: N-methylation of N-demethylstreptomycin.

Addition of dihydro-N-demethylstreptomycin (DH-NDMS)or N-demethylstreptomycin (NDMS)in a concentration of lOmg/ml to a growing culture of S. griseus blocked the de novo biosynthesis of streptomycin (SM). A simultaneous addition of 14CH3-L-methionine, however, led to specific N-methylation of the added compounds, thus giving the authentic antibiotics dihydrostreptomycin (DHS) and SM. By using the quantitative specific reaction of SM with bisulfite an electrophoresis system was developed capable of separating SM andDHS.