Combinatorial biosynthesis of 5-O-desosaminyl erythronolide A as a potent precursor of ketolide antibiotics |
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Authors: | Basnet Devi B Park Je Won Yoon Yeo Joon |
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Affiliation: | aDivision of Nano Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea |
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Abstract: | 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. |
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Keywords: | Ketolide antibiotics Erythromycin 5-O-Desosaminyl erythronolide A Combinatorial biosynthesis |
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