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Combinatorial biosynthesis of 5-O-desosaminyl erythronolide A as a potent precursor of ketolide antibiotics

Authors
Journal
Journal of Biotechnology
0168-1656
Publisher
Elsevier
Publication Date
Volume
135
Issue
1
Identifiers
DOI: 10.1016/j.jbiotec.2008.03.001
Keywords
  • Ketolide Antibiotics
  • Erythromycin
  • 5-O-Desosaminyl Erythronolide A
  • Combinatorial Biosynthesis

Abstract

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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