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-[1-¹⁴C, 2-³H]-and-[1-¹⁴C, 6-³H] 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 5-10μmoles per 100 ml of culture medium under conditions where the fermentation yielded approximately 20μmoles of streptozotocin in 24 hours gave incorporation rates which approached 40%. Upon feeding 100μmoles of either D-[1-^14C] glucosamine or L-[ureido-¹⁴C] citrulline they were incorporated into newly synthesized streptozotocin essentially without dilution by endogeneous precursors. D-[1-¹⁴C, 6-³H] Glucosamine was incorporated without change in T/C ratio while 20% of the tritium was lost from D-[1-¹⁴C, 2-³H] glucosamine, suggesting the possibility that D-glucosamine can partially equilibrate with D-fructose prior to its incorporation.