Studies on the biosynthesis of the antibiotic streptozotocin (streptozocin) by Streptomyces achromogenes var. streptozoticus. Feeding experiments with carbon-14 and tritium labelled precursors

Abstract

Feeding experiments and chemical degradations have shown that D-[1(-14)C,2(-3)H]-and-[1(-14)C,6(-3)H] glucosamine, L-[ureido-14C] citrulline, L-[guanidino-14C] arginine and L-[14CH3] methionine specifically label the glucosamine moiety, the urea carbonyl and the N-methyl group of the antibiotic streptozotocin, respectively. Feeding these precursors in amounts of 5 approximately 10 mumoles per 100 ml of culture medium under conditions where the fermentation yielded approximately 20 mumoles of streptozotocin in 24 hours gave incorporation rates which approached 40%. Upon feeding 100 mumoles of either D-[1(-14)C] glucosamine or L-[ureido-14C] citrulline they were incorporated into newly synthesized streptozotocin essentially without dilution by endogeneous precursors. D-[1(-14)C, 6(-3)H] Glucosamine was incorporated without change in T/C ratio while 20% of the tritium was lost from D-[1(-14)C,2(-3)H] glucosamine, suggesting the possibility that D-glucosamine can partially equilibrate with D-fructose prior to its incorporation.