Journal
ACS SYNTHETIC BIOLOGY
Volume 2, Issue 11, Pages 662-669Publisher
AMER CHEMICAL SOC
DOI: 10.1021/sb400058n
Keywords
natural products; silent pathways; genome mining; plug-and-play scaffold; synthetic biology; pathway assembly
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Funding
- National Academies Keck Futures Initiative on Synthetic Biology [NAKFI SB13]
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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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