title: Generation of New Complestatin Analogues by Heterologous Expression of the Complestatin Biosynthetic Gene Cluster from Streptomyces chartreusis AN1542.
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.
authors.affiliation: Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon, 34141, Republic of Korea.
authors.forename: Ok-Kyung
authors.initials: OK
authors.lastname: Park
authors.affiliation: Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon, 34141, Republic of Korea.
authors.forename: Ha-Young
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon, 34141, Republic of Korea.
authors.forename: Geon-Woo
authors.initials: GW
authors.lastname: Kim
authors.affiliation: Superbacteria Research Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon, 34141, Republic of Korea. wgkim@kribb.re.kr.
authors.forename: Won-Gon
authors.initials: WG
authors.lastname: Kim
mesh_terms: D000900:Anti-Bacterial Agents / Q000096:biosynthesis* / Q000737:chemistry / Q000494:pharmacology; D002733:Chlorophenols / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D005810:Multigene Family / Q000235:genetics*; D010456:Peptides, Cyclic / Q000096:biosynthesis* / Q000737:chemistry* / Q000494:pharmacology; D013302:Streptomyces / Q000187:drug effects / Q000235:genetics*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002733:Chlorophenols; D010456:Peptides, Cyclic; C023490:complestatin
keywords: antibiotics; biosynthesis; complestatin; cosmid assembly; heterologous expression