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Dr. Huy Thuan Nguyen
Center for Molecular Biology, Institute of Research and Development, Duy Tan University, Danang, Vietnam.
Title of the talk: Biotransformation of Flavonoid in genetically engineered Escherichia coli and Their Biological Activities
Flavonoids are the most ubiquitous polyphenolic secondary metabolites produced by plants. These polyphenols have been demonstrated as therapeutically valuable agents possessing anti-oxidant, anti-inflammatory, anti-proliferative activities, etc. These functional variations result mainly from the structural diversities that originate from various chemical modifications, such as glycosylation, methylation and hydroxylation. Recently, biotransformation-based modification has achieved significant progress due to advances in recombinant protein, DNA engineering, fermentation and computer-based modeling programs. Escherichia coli, a Gram-negative bacterium, is one of the most widely used platform microorganisms for the production of natural products, due to their well-characterized physiology, as well the abundance of genetic manipulations which are possible. Hence, the approach of using E. coli as a microbial factory to provide large quantity of value-added compounds for research, as well as human life, has been investigated. We designed the recombinant E. coli harboring activated sugar biosynthetic gene cluster (UDP-glucose or UDP-rhamnose) and suitable genes encoding glycosyltranferase or methyltransferase as host for biotransformation of substrates. Several flavonoid glycosides were successfully synthesized using various substrates such as flavonol (rhamnetin, myricetin, quercetin, kaempferol, morin), flavone (apigenin, baicalein), flavanonol (taxifolin) and flavonoid methoxides from isoflavonoid (genistein, daidzein) via whole-cell bioconversion under optimized culture conditions (DO, pH, temperature, carbon source). Based on regio-specific activity of biocatalyst, this approach was able to produce the high amount of products with low quality substrate, feasible, less by-product and effectively scale up the production of a number of specific flavonoid. The products were then used to test the growth inhibition of various cancer cell lines (A-549, B16F10, AGS, HepG2, PANC-1). It resulted significant changes in biological activity of modified flavonoids, in comparison to parent compounds. Collectively, biotransformation of flavonoids could be carried out using genetically engineered E. coli host as idea platform, and providing therapeutic flavonoid derivatives for subsequent pharmacological studies.
Nguyen Huy Thuan has completed his PhD in Department of Life Science and Biochemical Techniques, Sun Moon University, Asan city, Republic of Korea. His main areas of research interest is the biosynthesis of bioactive compounds using recombinant microorganism as Escherichi coli and actinomycetes.