Biosynthesis of desosamine: construction of a new macrolide carrying a genetically designed sugar moiety.
[formula: see text] The appended sugars in macrolide antibiotics are indispensable to the biological activities of these important drugs. In an effort to generate a set of novel macrolide derivatives, we have created a new analogue of methymycin and neomethymycin, antibiotics produced by Streptomyces venezuelae. This analogue 15 carrying a different sugar, D-quinovose, instead of D-desosamine, was constructed by taking advantage of targeted gene deletion combined with a specific pathway-independent C-3 reduction capability of the wild type S. venezuelae.
Borisova
S A
SA
Department of Chemistry, University of Minnesota, Minneapolis 55455, USA.
Zhao
L
L
Sherman
D H
DH
Liu
H W
HW
D000606:Amino Sugars / Q000096:biosynthesis* / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry; D002241:Carbohydrates / Q000737:chemistry*; D018942:Macrolides; D009154:Mutation; D011487:Protein Conformation; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
D000606:Amino Sugars; D000900:Anti-Bacterial Agents; D002241:Carbohydrates; D018942:Macrolides; C008517:methymycin; C008594:neomethymycin; C110125:desosamine