SBIR Phase I:Metabolic Engineering of Isoflavonoid Biosynthesis in Eschericia coli

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This Small Business Innovation Research Phase I research will create a biosynthetic system for economical, environmentally benign, versatile production of isoflavonoids, natural and non-natural. By transferring the optimal enzymes for the synthesis of isoflavonoids from plants into E. coli, the research will create self-replicating metabolic machines that convert inexpensive feedstocks into any of a diverse array of isoflavonoids determined by the precursors used and the enzymes added. Specifically, the research will co-develop the key enzymes in the biosynthesis of isoflavonoids and an E. coli strain adapted for the particular needs of these enzymes. This will provide a scaffold upon which other enzymes can be added to simultaneously create new isoflavonoids and the means of their production. Isoflavonoids are natural compounds from legumes that have great potential for improving human health. The simplest isoflavonoids , genistein and daidzein, have attracted clinical attention for their antioxidant and anticancer activities. More complex isoflavonoids such as puerarin and formononetin are also being evaluated for nutraceutical or pharmaceutical applications. Attracted by the numerous ways that isoflavonoids alter human cellular processes, chemists have begun to synthesize new generations of non-natural, isoflavonoid-based pharmaceutical candidates that might be more effective and specific than their natural precursors. In fact, some are already in clinical trials. The supply of isoflavonoids is based on extraction from plants, a process that is neither efficient nor consistent, and chemical synthesis which is excellent for some molecules but inefficient for others such as those that contains sugars or alkyl groups at specific positions on the isoflavonoid core structure. This process will expand the availability of these compounds and provide novel products for the benefit of the country.