Article ; Online: Expansion of bisindole biosynthetic pathways by combinatorial construction.
ACS synthetic biology
2015 Volume 4, Issue 6, Page(s) 682–688
Abstract: ... oxidoreductase genes from the phylogenetically related indolocarbazole rebeccamycin and staurosporine pathways ... of bisindole genes. The strategy for structural diversification we use here could furthermore be applied ... to other natural product families with known biosynthetic genes. ...
| Abstract | Cladoniamides are indolotryptoline natural products that derive from indolocarbazole precursors. Here, we present a microbial platform to artificially redirect the cladoniamide pathway to generate unnatural bisindoles for drug discovery. Specifically, we target glycosyltransferase, halogenase, and oxidoreductase genes from the phylogenetically related indolocarbazole rebeccamycin and staurosporine pathways. We generate a series of novel compounds, reveal details about the substrate specificities of a number of enzymes, and set the stage for future efforts to develop new catalysts and compounds by engineering of bisindole genes. The strategy for structural diversification we use here could furthermore be applied to other natural product families with known biosynthetic genes. |
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| MeSH term(s) | Biological Products/chemistry ; Biological Products/metabolism ; Carbazoles/chemistry ; Carbazoles/metabolism ; Genetic Engineering ; Indole Alkaloids/chemistry ; Indole Alkaloids/metabolism ; Metabolic Engineering ; Multigene Family ; Streptomyces/genetics ; Streptomyces/metabolism |
| Chemical Substances | Biological Products ; Carbazoles ; Indole Alkaloids ; rebeccamycin (93908-02-2) |
| Language | English |
| Publishing date | 2015-01-02 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 2161-5063 |
| ISSN (online) | 2161-5063 |
| DOI | 10.1021/sb5003218 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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