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ACS Synth Biol. 2013 Nov 15;2(11):662-9. doi: 10.1021/sb400058n. Epub 2013 Aug 22.

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

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Department of Chemical and Biomolecular Engineering, ‡Department of Chemistry, and §Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.


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.

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