High Cell Density Fermentation for Production of Flavonoids using Recombinant E.coli in a Bioreactor
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Flavonoids are a diverse group of plant secondary metabolites. These phytochemicals belonging to the class of polyphenols have demonstrated assortment of pharmaceutical and nutraceutical properties which includes anti-oxidant, anti-microbial, anti-viral, anti-cancer, anti-diabetic, anti-cardiovascular etc. With the demand for flavonoid dietary supplements increasing, the current production practices of plant extraction and chemical synthesis exhibit significant drawbacks of low yield, lack of stereo selectivity, high cost and use of toxic chemicals and catalysts. We demonstrate that microbial production platform offers high yields with ease of scale up and eco - friendly cost effective processes. In our current project we have carried out multivariable optimization of fermentation parameters and investigated the effects of media composition, inducer concentration, carbon source and precursor concentration for the production of dihydrokaempferol (dihydroflavonol) consuming naringenin (flavonone) as substrate using recombinant E.coli harboring the Flavonone 3β Hydroxylase (FHT) gene. We have successfully optimized the fermentation protocol and scaled up the operation in 2 L bioreactor and increased the volumetric productivity by 6 folds compared to shake flasks. These results successfully validate the use of bioreactor based systems for commercial production of flavonoids.