Nature’s combinatorial biosynthesis and recently engineered production of nucleoside antibiotics in Streptomyces

Shawn Chen, William A. Kinney, Steven Van Lanen

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations

Abstract

Modified nucleosides produced by Streptomyces and related actinomycetes are widely used in agriculture and medicine as antibacterial, antifungal, anticancer and antiviral agents. These specialized small-molecule metabolites are biosynthesized by complex enzymatic machineries encoded within gene clusters in the genome. The past decade has witnessed a burst of reports defining the key metabolic processes involved in the biosynthesis of several distinct families of nucleoside antibiotics. Furthermore, genome sequencing of various Streptomyces species has dramatically increased over recent years. Potential biosynthetic gene clusters for novel nucleoside antibiotics are now apparent by analysis of these genomes. Here we revisit strategies for production improvement of nucleoside antibiotics that have defined mechanisms of action, and are in clinical or agricultural use. We summarize the progress for genetically manipulating biosynthetic pathways for structural diversification of nucleoside antibiotics. Microorganism-based biosynthetic examples are provided and organized under genetic principles and metabolic engineering guidelines. We show perspectives on the future of combinatorial biosynthesis, and present a working model for discovery of novel nucleoside natural products in Streptomyces.

Original languageEnglish
Article number66
JournalWorld Journal of Microbiology and Biotechnology
Volume33
Issue number4
DOIs
StatePublished - Apr 1 2017

Bibliographical note

Publisher Copyright:
© 2017, Springer Science+Business Media Dordrecht.

Keywords

  • Gene clusters
  • Metabolic engineering
  • Natural product biosynthesis
  • Nucleoside antibiotics
  • Streptomyces

ASJC Scopus subject areas

  • Biotechnology
  • Physiology
  • Applied Microbiology and Biotechnology

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