Enzymic Studies on the Biosynthesis of Streptomycin

TRANSAMIDINATION OF INOSAMINE AND STREPTAMINE DERIVATIVES

From the ¹ From the Department of Biology, William Marsh Rice University, Houston, Texas 77001

1. Heat extracts of mature mycelia of streptomycin-producing strains of Streptomyces contain two compounds which, when incubated with arginine-guanidino-¹⁴C plus a crude enzyme preparation from S. griseus ATCC 12475 containing arginine : X amidinotransferase, give products detected as radioactive Peaks I and II. Heat extracts from S. bluensis var. bluensis, which synthesizes bluensomycin, a monoguanidinated analogue of streptomycin, give only Peak I. A number of Streptomyces strains which do not produce streptomycin and which normally give neither Peak I nor Peak II give Peak II after exposure during growth to added streptidine. Evidence is presented that Peak I is N-amidino-scyllo-inosamine-P and Peak II is streptidine-P.

2. Purified amidinotransferase preparations from derepressed S. griseus ATCC 12475 and S. bikiniensis, both streptomycin producers, and a crude enzyme preparation from S. bluensis catalyze the following transamidinations with chemically phosphorylated acceptor compounds: arginine : scyllo-inosamine-P, arginine: streptamine-P, and arginine : 2-deoxystreptamine-P. In each case only one amino group is transamidinated, with the respective formation of N-amidino - scyllo - inosamine - P, N - amidinostreptamine - P, and N-amidino-2-deoxystreptamine-P. Location of the single phosphate group is unknown. Treatment with alkaline phosphatase gives the corresponding dephosphorylated derivatives.

3. Crude enzyme preparations from S. griseus and S. bikiniensis catalyze incorporation of radioactivity from arginine-guanidino-¹⁴C into streptidine-P after a lag period which is eliminated following preincubation in the absence of arginine. Preincubation presumably transforms streptidine-P into the actual amidine acceptor, which can now react more rapidly with purified amidinotransferases and the S. bluensis enzyme.

4. A scheme for biosynthesis of the streptidine moiety of streptomycin, the bluensidine moiety of bluensomycin, and the deoxystreptamine moieties of kanamycin and neomycin is presented.

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