28(C-4) 2-デオキシストレプタミン含有アミノ配糖体抗生物質のコア構造の生合成(口頭発表の部)

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The biosynthesis of clinically important aminocyclitol antibiotics, particularly containing 2-deoxystreptamine (DOS), has been studied. Recently, we identified the butirosin biosynthetic gene cluster from Bacillus circulans, however, most of the ORFs could not been functionally identified by means of simple homology search. We envisioned, therefore, that related biosynthetic gene clusters of similar DOS-containing aminoglycoside antibitotics may give significant information as to the crucial biosynthetic genes for the core structure of the antibiotic. Thus, the neomycin biosynthetic gene cluster has been tackled and identified accordingly from Streptotnyces fradiae. As a result, most of the btr genes were found in the neomycin gene cluster, which appears to suggest that those genes are responsible for the biosynthesis of the core ribostamycin in both antibiotics. Our attention was next turned to the enzymatic reaction by each biosynthetic gene product, particularly for the core structure biosynthesis. As a result of the btrD gene disruption, BtrD was suggested to be involved in the preparation of glycosyl donor prior to the glycosylation of DOS. BtrD was expressed in E. coli and was found to be a novel nucleotidylyltransferase, which synthesizes UDP-glucosamine from UTP and GlcN-1-P, although no significant homology was found between BtrD and the well known dTDP-glucose synthase. BtrS was shown to be a dual functional aminotransferase in the DOS biosynthesis by gene disruption studies. Precise mechanistic and stereochemical studies of BtrS reaction showed that BtrS can distinguish prochirality of DOS, where the chirality of DOI was not strictly distinguished. These results suggested that the α-positions of the inosose carbonyl are not the determining element of recognition, but rather a plausible hydrogen-bonding at one of the β-positions of inosose carbonyl should be significant.
天然有機化合物討論会の論文
2004-10-01

28(C-4) 2-デオキシストレプタミン含有アミノ配糖体抗生物質のコア構造の生合成(口頭発表の部)

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