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Refactoring The Silent Spectinabilin Gene Cluster Using A Plug-And-Play Scaffold, Zengyi Shao, Guodong Rao, Chun Li, Zhanar Abil, Yunzi Luo, Huimin Zhao
Refactoring The Silent Spectinabilin Gene Cluster Using A Plug-And-Play Scaffold, Zengyi Shao, Guodong Rao, Chun Li, Zhanar Abil, Yunzi Luo, Huimin Zhao
Zengyi Shao
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 …
Activation And Characterization Of A Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster, Yunzi Luo, Hua Huang, Jing Liang, Meng Wang, Lu Lu, Zengyi Shao, Ryan E. Cobb, Huimin Zhao
Activation And Characterization Of A Cryptic Polycyclic Tetramate Macrolactam Biosynthetic Gene Cluster, Yunzi Luo, Hua Huang, Jing Liang, Meng Wang, Lu Lu, Zengyi Shao, Ryan E. Cobb, Huimin Zhao
Zengyi Shao
Polycyclic tetramate macrolactams (PTMs) are a widely distributed class of natural products with important biological activities. However, many of these PTMs have not been characterized. Here we apply a plug-and-play synthetic biology strategy to activate a cryptic PTM biosynthetic gene cluster SGR810-815 from Streptomyces griseus and discover three new PTMs. This gene cluster is highly conserved in phylogenetically diverse bacterial strains and contains an unusual hybrid polyketide synthase-nonribosomal peptide synthetase, which resembles iterative polyketide synthases known in fungi. To further characterize this gene cluster, we use the same synthetic biology approach to create a series of gene deletion constructs and …