Production of a Novel Quercetin Glycoside through Metabolic Engineering of Escherichia coli
Open Access
- 15 June 2012
- journal article
- research article
- Published by American Society for Microbiology in Applied and Environmental Microbiology
- Vol. 78 (12), 4256-4262
- https://doi.org/10.1128/aem.00275-12
Abstract
Most flavonoids exist as sugar conjugates. Naturally occurring flavonoid sugar conjugates include glucose, galactose, glucuronide, rhamnose, xylose, and arabinose. These flavonoid glycosides have diverse physiological activities, depending on the type of sugar attached. To synthesize an unnatural flavonoid glycoside, Actinobacillus actinomycetemcomitans gene tll (encoding dTDP-6-deoxy- l -lyxo-4-hexulose reductase, which converts the endogenous nucleotide sugar dTDP-4-dehydro-6-deoxy- l -mannose to dTDP-6-deoxytalose) was introduced into Escherichia coli . In addition, nucleotide-sugar dependent glycosyltransferases (UGTs) were screened to find a UGT that could use dTDP-6-deoxytalose. Supplementation of this engineered strain of E. coli with quercetin resulted in the production of quercetin-3- O -(6-deoxytalose). To increase the production of quercetin 3- O -(6-deoxytalose) by increasing the supplement of dTDP-6-deoxytalose in E. coli , we engineered nucleotide biosynthetic genes of E. coli , such as galU (UTP-glucose 1-phosphate uridyltransferase), rffA (dTDP-4-oxo-6-deoxy- d -glucose transaminase), and/or rfbD (dTDP-4-dehydrorahmnose reductase). The engineered E. coli strain produced approximately 98 mg of quercetin 3- O -(6-deoxytalose)/liter, which is 7-fold more than that produced by the wild-type strain, and the by-products, quercetin 3- O -glucose and quercetin 3- O -rhamnose, were also significantly reduced.Keywords
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