Journal
JOURNAL OF BIOTECHNOLOGY
Volume 135, Issue 1, Pages 92-96Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jbiotec.2008.03.001
Keywords
ketolide antibiotics; erythromycin; 5-O-desosaminyl erythronolide A; combinatorial biosynthesis
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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. (C) 2008 Elsevier B.V. All rights reserved.
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