CHEMOPREVENTIVE ISOFLAVONES FROM MICROORGANISMS

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Flavonoids ar plant substances that give flowers and fruits their color, and they are included in a normal diet. The isoflavones are a class of flavonoids found in soybean. Epidemiological studies have shown that in geographic areas where diets are rich in soybeans there is a reduced incidence of breast cancer Genistein is an isoflavone whose presence in soybeans has been linked to the chemopreventive effect. Genistein is also an inhibitor of topoisomerase II and protein tyrosine kinase. Because these two enzymes are involved in cellular differentiation and proliferation, genistein could also have chemotherapeutic properties. Much needed biomedical research on geneistein is currently inhibited by the high cost of the pure compound synthetically produced or extracted from soybeans. Microorganisms have also been reported to produce genistein and could provide an economical source for the compound. Microbial fermentations are characteristically amenable to process improvement through genetic and physiological manipulations. In phase one we propose to confirm microbial production of isoflavones and begin to develop the tools needed for genetic and biochemical analysis of isoflavone production. In phase 2, we hope to create an efficient fermentation or microbial transformation process and use targeted genetics to produce new isoflavone analogs for biological testing.