Development of anti-cancer drug candidate using biosynthetic and chemical engineering

Leukemia is one of the major types of cancer with over 330.000 new incidences each year worldwide. Therapeutic options for treating leukemia are relatively limited, and there exists an unmet need in safe and efficient anti-leukemic drugs. The major goal o f the proposed project is to develop an anti-cancer drug candidate for treatment of leukemia using innovative approach of combined biosynthetic and chemical engineering of a macrolactam antibiotic. This goal will be achieved by a concerted effort from the project partners with expertise in engineered antibiotic biosynthesis, fermentation technologies, chemical synthesis, molecular biology of cancer, and pre-clinical testing of drug candidates. A series of analogues of a cytotoxic macrolactam antibiotic wi ll first be generated through biosynthetic and chemical engineering. The analogues, along with the "mother" compound, will be extensively tested in vitro in order to unravel the mechanism of anti-cancer activity, to study the structure-activity relationsh ip, and to select the most promising compounds. Next, the analogues chosen will be tested for toxicity and anti-cancer activity in animal model at the University of Bergen, allowing selection of a drug candidate that can be further developed into an anti- leukemic drug.