Journal
CHEMBIOCHEM
Volume 17, Issue 18, Pages 1725-1731Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600241
Keywords
antibiotics; biosynthesis; complestatin; cosmid assembly; heterologous expression
Funding
- Intelligent Synthetic Biology Center of Global Frontier Project - Ministry of Education, Science and Technology [2011-0031944]
- KRIBB Research Initiative Program, Republic of Korea
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The heterologous expression of the biosynthetic gene cluster (BGC) of natural products enables the production of complex metabolites in a well-characterized host, and facilitates the generation of novel analogues by the manipulation of the genes. However, the BGCs of glycopeptides such as vancomycin, teicoplanin, and complestatin are usually too large to be directly cloned into a single cosmid. Here, we describe the heterologous expression of the complestatin BGC. The 54.5kb cluster was fully reconstituted from two overlapping cosmids into one cosmid by -RED recombination-mediated assembly. Heterologous expression of the assembled gene cluster in Streptomyces lividans TK24 resulted in the production of complestatin. Deletion of cytochrome P450 monooxygenase genes (open reading frames 10 and 11) and heterologous expression of the modified clusters led to the production of two new monocyclic and linear derivatives, complestatinsM55 and S56.
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