Refactoring the silent spectinabilin gene cluster using a plug-and-play scaffold

Zengyi Shao, Guodong Rao, Chun Li, Zhanar Abil, Yunzi Luo, Huimin Zhao

Research output: Contribution to journalArticlepeer-review

Abstract

Natural products (secondary metabolites) are a rich source of compounds with important biological activities. Eliciting pathway expression is always challenging but extremely important in natural product discovery because an individual pathway is tightly controlled through a unique regulation mechanism and hence often remains silent under the routine culturing conditions. To overcome the drawbacks of the traditional approaches that lack general applicability, we developed a simple synthetic biology approach that decouples pathway expression from complex native regulations. Briefly, the entire silent biosynthetic pathway is refactored using a plug-and-play scaffold and a set of heterologous promoters that are functional in a heterologous host under the target culturing condition. Using this strategy, we successfully awakened the silent spectinabilin pathway from Streptomyces orinoci. This strategy bypasses the traditional laborious processes to elicit pathway expression and represents a new platform for discovering novel natural products.

Original languageEnglish (US)
Pages (from-to)662-669
Number of pages8
JournalACS synthetic biology
Volume2
Issue number11
DOIs
StatePublished - Nov 15 2013

Keywords

  • genome mining
  • natural products
  • pathway assembly
  • plug-and-play scaffold
  • silent pathways
  • synthetic biology

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • Biomedical Engineering

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