BIOSYNTHESIS OF BUTIROSINS. II

BIOSYNTHETIC PATHWAY OF BUTIROSINS ELUCIDATED FROM COSYNTHESIS AND FEEDING EXPERIMENTS

Abstract

By cosynthetic studies, nine butirosin-non-producing blocked mutants of Bacillus circulans were classified into 7 groups (A to F and exceptional groups), based on their complementation patterns. Except for two strains of group A, mutant strains were all neamine-requiring idiotrophs. Mutants of group A produced xylostasin and ribostamycin and a mutant of group B accumulated 2-deoxystreptamine (DOS) in the culture broth. By feeding tests with a compound assumed to be an intermediate in butirosin biosynthesis, the following information was obtained: myo-inositol, conduritol B, 1-deoxy-scyllo-inositol and its per-acetate were not incorporated into the antibiotic by any mutants. 2-Deoxy-scyllo-inosose was converted to butirosins only by mutants of groups E and F. These mutants converted scyllo-inosose to 2-hydroxybutirosins, as well. 2-Deoxy-scyllo-inosamine and DOS, but not N-acetyl-DOS, were converted to butirosins by mutants of groups C to F. These mutants also converted
scyllo-inosamine-2 and streptamine to 2-hydroxybutirosins. Paromamine, neamine, ribostamycin and xylostasin were readily converted to butirosins by all mutants except those of group A. Mutants of group A could not convert any substances tested. By the above information, the biosynthetic pathway previous proposed for butirosins was extended as shown in Fig. 4, which indicated the blocked sites in the respective mutants.