Heterologous production of ribostamycin derivatives in engineered Escherichia coli

Nagendra Prasad Kurumbang, Je Won Park, Yeo Joon Yoon, Kwangkyoung Liou, Jae Kyung Sohng

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Aminoglycosides are a class of important antibiotic compounds used for various therapeutic indications. In recent times, their efficacy has been curtailed due to the rapid development of bacterial resistance. There is a need to develop novel derivatives with an improved spectrum of activity and higher sensitivity against pathogenic bacteria. Although efforts have been focused on the development of newer therapeutic agents by chemical synthesis, to our knowledge, there has been no attempt to harness the potential of microorganisms for this purpose. Escherichia coli affords a widely studied cellular system that could be utilized not only for understanding but also for attempting to engineer the biosynthetic pathway of secondary metabolites. The primary metabolic pathway of E. coli can be engineered to divert the precursor pool required for the biosynthesis of secondary metabolites. Utilizing this approach previously, we engineered E. coli host and generated E. coli M1. Here, we produced a ribostamycin derivative in the engineered host by heterologous expression of the recombinants constructed from the genes encoding the biosynthetic pathway in aminoglycoside-producing strains. The products obtained from the transformants were isolated, analyzed and verified to be ribostamycin derivatives. The study further demonstrated the importance of E. coli as surrogate antibiotic producer and also offered future possibility for the production of other aminoglycoside derivatives through genetic engineering and expression in a heterologous background.

Original languageEnglish
Pages (from-to)526-533
Number of pages8
JournalResearch in Microbiology
Volume161
Issue number7
DOIs
Publication statusPublished - 2010 Sep 1
Externally publishedYes

Keywords

  • 2-Deoxystreptamine
  • Aminoglycosides
  • Co-expression
  • Eengineered Escherichia coli
  • Heterologous production

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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