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Seminars
Engineering of flavonoid biosynthesis in yeast
John Morgan
Department of Chemical Engineering
Purdue University
When: Thursday, October 6, 2005
Time: 2:30 PM to 3:30 PM
Where: 1064 Duncall Hall
Abstract:
The phenylpropanoid pathway is a metabolic route that leads to the synthesis of thousands of plant natural products such as flavonoids and lignin. Several of these compounds impact human health via anti-oxidant, estrogen mimic and anti-cancer activities. Our group is interested in the production of valuable compounds from the phenylpropanoid pathway. Currently, these compounds are derived from plant extracts or synthetic organic chemistry. The plant extraction method suffers from having to purify compounds from complex mixtures of low concentrations. On the other hand, the total organic synthesis route typically results in poor yields of racemic mixtures of products. Metabolic engineering of the phenylpropanoid pathway into a foreign host is a method to increase the productivity of specific compounds, overcoming the limitations of the other methods. We have reconstructed the initial ‘core’ enzymatic steps of the flavonoid pathway by heterologous expression of cinnamate-4-hydroxylase (C4H), 4-coumarate: coenzyme A ligase (4CL), and chalcone synthase (CHS) in Saccharomyces cerevisiae. Building upon this core pathway, we have expressed additional enzymes enabling the synthesis of apigenin and chrysin, two flavones with anti-cancer activity. As there is a high burden on the host with the simultaneous expression of 5 foreign enzymes, strategies to increase the metabolic flux to the final products will be presented. We will also present work on the production of non-natural flavonoids as potential pharmaceutical leads from the engineered yeast cultures.
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