ROLE OF PSEUDO-DISACCHARIDE NEAMINE AS AN INTERMEDIATE IN BIOSYNTHESIS OF NEOMYCIN

By using wild-type and deoxystreptamine-negative mutants of Streptomyces fradiae grown in media containing [6-3H]glucose or [U-14C]glucose, and by subsequent hydrolysis of the labeled neomycin produced, neamines labeled with 3H in rings I and II, but with 14C in ring I only, were prepared. A mixture of these 2 forms of neamine was converted by deoxystreptamine-negative S. rimosus f. paromomycinus into neomycin (not paromomycin) with a 30% yield. The 3H:14C ratio in this neomycin was the same as that measured in neamine produced by hydrolysis of the neomycin, and in unused neamine reisolated from the incubation medium. The 3H:14C ratio in the neomycin was not affected by the presence of unlabeled deoxystreptamine during the incubation. The radioactivity in the neomycin was associated with rings I and II only. The added neamine is apparently incorporated into antibiotic intact, without initial hydrolysis, and the probably 1st step in the subunit assembly of neomycin is the formation of neamine.