Combinatorial biosynthesis of 5-O-desosaminyl erythronolide A as a potent precursor of ketolide antibiotics.
Ketolides, characterized by possessing a 3-keto group in place of the l-cladinose moiety of erythromycin A, are the recent generation of antimicrobials derived semi-synthetically from the 14-membered ring macrolide erythromycin A. The multi-step synthetic route to ketolides can be shortened by using 5-O-desosaminyl erythronolide A as a precursor, which reduces the steps for the removal of l-cladinose attached at the C-3 position in erythromycin A. Deletion of an eryBV gene encoding mycarosyl glycosyltransferase in the erythromycin-producer Saccharopolyspora erythraea resulted in the accumulation of 5-O-desosaminyl erythronolide B. In vivo expression of the cytochrome P450 gene pikC, which encodes the substrate-flexible hydroxylase from the pikromycin biosynthetic pathway of Streptomyces venezuelae, in the eryBV deletion mutant strain of Sac. erythraea led to 5-O-desosaminyl erythronolide A production.
Basnet
Devi B
DB
Division of Nano Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
Park
Je Won
JW
Yoon
Yeo Joon
YJ
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000096:biosynthesis; D024861:Genetic Enhancement / Q000379:methods*; D048628:Ketolides / Q000737:chemistry*; D016930:Saccharopolyspora / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D048628:Ketolides; C010708:5-O-desosaminylerythronolide A oxime; D004917:Erythromycin