Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17

Pramod B. Shinde, Ah Reum Han, Jaeyong Cho, So Ra Lee, Yeon Hee Ban, Young Ji Yoo, Eun Ji Kim, Eunji Kim, Myoung Chong Song, Je Won Park, Dong Gun Lee, Yeo Joon Yoon

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Expression plasmids carrying different deoxysugar biosynthetic gene cassettes and the gene encoding a substrate-flexible glycosyltransferase DesVII were constructed and introduced into Streptomyces venezuelae YJ003 mutant strain bearing a deletion of a desosamine biosynthetic (des) gene cluster. The resulting recombinants produced macrolide antibiotic YC-17 analogs possessing unnatural sugars replacing native d-desosamine. These metabolites were isolated and further purified using chromatographic techniques and their structures were determined as d-quinovosyl-10-deoxymethynolide, l-rhamnosyl-10-deoxymethynolide, l-olivosyl-10-deoxymethynolide, and d-boivinosyl-10-deoxymethynolide on the basis of 1D and 2D NMR and MS analyses and the stereochemistry of sugars was confirmed using coupling constant values and NOE correlations. Their antibacterial activities were evaluated in vitro against erythromycin-susceptible and -resistant Enterococcus faecium and Staphylococcus aureus. Substitution with l-rhamnose displayed better antibacterial activity than parent compound YC-17 containing native sugar d-desosamine. The present study on relationships between chemical structures and antibacterial activities could be useful in generation of novel advanced antibiotics utilizing combinatorial biosynthesis approach.

Original languageEnglish
Pages (from-to)142-148
Number of pages7
JournalJournal of Biotechnology
Volume168
Issue number2
DOIs
Publication statusPublished - 2013 Oct 1
Externally publishedYes

    Fingerprint

Keywords

  • Combinatorial biosynthesis
  • Macrolides
  • Streptomyces venezuelae
  • YC-17

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Shinde, P. B., Han, A. R., Cho, J., Lee, S. R., Ban, Y. H., Yoo, Y. J., Kim, E. J., Kim, E., Song, M. C., Park, J. W., Lee, D. G., & Yoon, Y. J. (2013). Combinatorial biosynthesis and antibacterial evaluation of glycosylated derivatives of 12-membered macrolide antibiotic YC-17. Journal of Biotechnology, 168(2), 142-148. https://doi.org/10.1016/j.jbiotec.2013.05.014