Tuesday, July 31, 2007 - 4:00 PM
S106
A systems biology approach for plant secondary metabolite optimization in microorganisms
Mattheos A.G. Koffas, Chemical and Biological Engineering, University at Buffalo, the State University of New York, North Campus, 904 Furnas Hall, Buffalo, NY 14260
Flavonoids are a diverse group of secondary metabolites found ubiquitously in the plant kingdom. Many flavonoids are used as nutraceutical supplements but a growing number of unnatural flavonoids are being investigated as therapeutic agents. Our group has been focusing on utilizing metabolic engineering to synthesize natural plant flavonoids (isoflavones, flavanones, flavones, dihydroflavonols, stilbenes, flavonols, catechins and anthocyanins) and stilbenes such as resveratrol in microorganisms and their use for diabetes and obesity treatment. Our progress has covered the reconstruction of the plant biosynthetic pathways within both Escherichia coli and Saccharomyces cerevisiae. The combination of organic synthesis with metabolic engineering has allowed us to explore the synthesis of novel flavonoid analogs using mutasynthesis approaches. For example, through such strategies, microbial biocatalysts have been able to produce fluorinated and aminated flavonoids as well as flavonoids with unique acrylic acids substituting their phenyl rings. Robust synthesis of the various derivatives allowed the structure-function analysis of inhibitory properties against α-glucosidase, an enzyme responsible of glucose assimilation in digestive track that has been the target of various drugs for type II diabetes treatment. Results will be presented demonstrating increased enzyme inhibition with the number of B-ring hydroxyl groups in stilbene derivatives. In addition, novel chemical structures will be presented that demonstrate more potent inhibitory effects than drugs currently in the market, such as acarbose. Overall, our work has demonstrated a unique blending of organic synthesis with metabolic engineering for the purpose of efficient nutraceutical and pharmaceutical development and production.