Novel Artificial Natural Products Against Breast Cancer Through Combinatorial Biosynthesis
Abstract
The technique of combinatorial biosynthesis was applied, to generate derivatives (analogs) of various anticancer drugs, including aureolic acids (mithramycin), angucyclins (landomycins, urdamycins, oviedomycin), anthracycline-like compounds (elloramycins), and indolcarbazoles (rebeccamycin) . In addition, a novel derivative of mitomycin was synthesized. The hypothesis could be proven that novel mithramycin analogs with modifications in the sugar moieties and the pentyl side chain could be generated through inactivation of methyltransferase and ketoreductase encoding genes. The recombination of landomycin glycosyltransferase encoding genes with genes of the urdamyciun pathway led to novel urdamycin derivatives, and methyltransferases and the glycosyl transferase of the elloramycin gene cluster were investigated, yielding various new elloramycin analogs. In addition, the gene cluster of the indolcarbazole drug rebeccamycin was unrevealed and investigated, and the novel angucyclinone drug oviedomycin has been discovered through heterologous expression of its gene cluster. Many of the new drugs show antiproliferative activities and are potential drugs against breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADB283939
Entities
People
- Jürgen Rohr
Organizations
- Medical University of South Carolina