Chemopreventive Isoflavones from Microorganisms

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