PRODUCING NATURAL BETA-CAROTENE FOR CHEMOTHERAPEUTIC USE

BETA-CAROTENE (PROVITAMIN A) HAS RECENTLY BEEN SHOWN TO BE AN EFFECTIVE CHEMOTHERAPEUTIC AGENT IN THE TREATMENT AND PREVENTION OF CANCER. MOREOVER, CAROTENES PRODUCED BIOSYNTHETICALLY (CONTAINING 9-CIS ISOMERS) APPEAR TO BE A MORE EFFECTIVE ANTITUMOR AGENTS THAN THOSE PRESENTLY MANUFACTURED CHEMICALLY (ALL-TRANS ISOMERS). AT PRESENT, THERE IS NO COST COMPETITIVE PROCESS OF BIOSYNTHETICALLY PRODUCING BETA-CAROTENE. WE HAVE IDENTIFIED A MICROALGAL SPECIES WHICH CAN BE GROWN UNDER CONVENTIONAL, CLEAN-ROOM, FERMENTATION CONDITIONS, AND PRODUCES A MIXTURE OF BETA-CAROTENE AND GAMMA-CAROTENE. THE GOAL OF THIS RESEARCH PROJECT IS TO PRODUCE A PHARMACEUTICAL GRADE BETA-CAROTENE UNDER ASEPTIC CONDITIONS AT A COST COMPETITIVE WITH THE CHEMICAL SYNTHESIS ROUTE. IN PHASE I, WE SHALL BEGIN THE OPTIMIZATION OF THE BETA-CAROTENE PRODUCTIVITY OF THIS MICROORGANISM THROUGH IMPROVEMENTS TO THE MEDIUM COMPOSITION AND THE PHYSICAL PARAMETERS OF THE FERMENTATION. WE SHALL ALSO SCREEN FOR OVERPRODUCING CLONE LINES WHICH MAY HAVE A DEREGULATED BIOSYNTHETIC PATHWAY. ON THE BASIS OF THESE PRELIMINARY RESULTS WE WILL BE ABLE TO DETERMINE THE ECONOMIC FEASIBILITY OF THE OVERALL APPROACH. DURING PHASE II, THE OPTIMIZATION AND SCALE-UP DEVELOPMENT WILL CONTINUE IN PREPARATION TO ESTABLISHING A COMMERCIAL SCALE PROCESS.