Elaboration of neosamine rings in the biosynthesis of neomycin and butirosin

被引:45
作者
Huang, Fanglu [1 ]
Spiteller, Dieter [1 ]
Koorbanally, Neil A. [1 ]
Li, Yanyan [1 ]
Llewellyn, Nicholas M. [1 ]
Spencer, Jonathan B. [1 ]
机构
[1] Univ Cambridge, Univ Chem Lab, Cambridge CB2 1EW, England
关键词
aminoglycosides; biosynthesis; butirosin neomycin; oxidases; transferases;
D O I
10.1002/cbic.200600371
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of Streptomyces fradiae NCIMB 8233 hove been characterized as glucosaminyl-6'-oxidase and 6'-oxoglucosammyi-nyl:L-glutamate aminotransferase, respectively. The joint activity of Neo-11 and Neo-18 is responsible for the conversion of paromamine to neamine in the biosynthetic pathway of neomycin through a mechanism of FAD-dependent dehydrogenation followed by a pyridoxal-5'-phosphate-mediated transamination. Neo-18 is also shown to catalyze deamination at C-6''' of neomycin, thus suggesting bifunctional roles of the two enzymes in the formation of both neosamine rings of neomycin. The product of the btrB gene, a homologue of neo-18 in the butirosin biosynthetic gene cluster (btr) in Bacillus circulans, exhibits the same activity as Neo-18; this indicates that there is a similar reaction sequence in both butirosin and neomycin biosynthesis.
引用
收藏
页码:283 / 288
页数:6
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