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

Devi B. Basnet, Je Won Park, Yeo Joon Yoon

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)92-96
Number of pages5
JournalJournal of Biotechnology
Volume135
Issue number1
DOIs
Publication statusPublished - 2008 May 20
Externally publishedYes

Keywords

  • 5-O-Desosaminyl erythronolide A
  • Combinatorial biosynthesis
  • Erythromycin
  • Ketolide antibiotics

ASJC Scopus subject areas

  • Biotechnology

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