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Title 

Generation of new complestatin analogues by heterologous expression of the complestatin biosynthetic gene cluster from Streptomyces chartreusis AN1542

Authors 

Ok Kyung ParkHa Young ChoiGeon Woo KimWon Gon Kim

Publisher 

Wiley-Blackwell

Issue Date 

2016

Citation 

ChemBioChem, vol. 17, no. 18, pp. 1725-1731

Keywords 

antibioticsbiosynthesiscomplestatincosmid assemblyheterologous expression

Abstract 

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 54.5 kb cluster was fully reconstituted from two overlapping cosmids into one cosmid by λ-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, complestatins M55 and S56.

ISSN 

1439-4227

Link 

http://dx.doi.org/10.1002/cbic.201600241

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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