Elaboration of neosamine rings in the biosynthesis of neomycin and butirosin.
The proteins Neo-11 and Neo-18 encoded in the neomycin gene cluster (neo) of Streptomyces fradiae NCIMB 8233 have been characterized as glucosaminyl-6'-oxidase and 6'-oxoglucosaminyl: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.
Huang
Fanglu
F
University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
Spiteller
Dieter
D
Koorbanally
Neil A
NA
Li
Yanyan
Y
Llewellyn
Nicholas M
NM
Spencer
Jonathan B
JB
D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D001407:Bacillus / Q000201:enzymology / Q000235:genetics; D002076:Butirosin Sulfate / Q000096:biosynthesis*; D002240:Carbohydrate Sequence; D003500:Cyclization; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000145:classification; D008969:Molecular Sequence Data; D005810:Multigene Family; D009355:Neomycin / Q000096:biosynthesis*; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics; D000637:Transaminases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; C038761:neosamine C; D002076:Butirosin Sulfate; D010088:Oxidoreductases; D000637:Transaminases; D009355:Neomycin; D005944:Glucosamine