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Regioselective synthesis of flavonoid bisglycosides using Escherichia coli harboring two glycosyltransferases

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Abstract

Regioselective glycosylation of flavonoids cannot be easily achieved due to the presence of several hydroxyl groups in flavonoids. This hurdle could be overcome by employing uridine diphosphate-dependent glycosyltransferases (UGTs), which use nucleotide sugars as sugar donors and diverse compounds including flavonoids as sugar acceptors. Quercetin rhamnosides contain antiviral activity. Two quercetin diglycosides, quercetin 3-O-glucoside-7-O-rhamnoside and quercetin 3,7-O-bisrhamnoside, were synthesized using Escherichia coli expressing two UGTs. For the synthesis of quercetin 3-O-glucoside-7-O-rhamnoside, AtUGT78D2, which transfers glucose from UDP-glucose to the 3-hydroxyl group of quercetin, and AtUGT89C1, which transfers rhamnose from UDP-rhamnose to the 7-hydroxyl group of quercetin 3-O-glucoside, were transformed into E. coli. Using this approach, 67 mg/L of quercetin 3-O-glucoside-7-O-rhamnoside was synthesized. For the synthesis of quercetin 3,7-O-bisrhamnoside, AtUGT78D1, which transfers rhamnose to the 3-hydroxy group of quercetin, and AtUGT89C1 were used. The RHM2 gene from Arabidopsis thaliana was coexpressed to supply the sugar donor, UDP-rhamnose. E. coli expressing AtUGT78D1, AtUGT89C1, and RHM2 was used to obtain 67.4 mg/L of quercetin 3,7-O-bisrhamnoside.

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Acknowledgments

This work was supported by a grant from Next-Generation BioGreen 21 Program (PJ00948301), Rural Development Administration, Republic of Korea and by the Priority Research Centers Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012–0006686).

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Authors and Affiliations

  1. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, 1 Hwayang-Dong, Gwangjin-gu, Seoul, 143-701, South Korea

    Hyeon Jeong Kim, Bong-Gyu Kim & Joong-Hoon Ahn

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  1. Hyeon Jeong Kim
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  2. Bong-Gyu Kim
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  3. Joong-Hoon Ahn
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Correspondence to Joong-Hoon Ahn.

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Kim, H.J., Kim, BG. & Ahn, JH. Regioselective synthesis of flavonoid bisglycosides using Escherichia coli harboring two glycosyltransferases. Appl Microbiol Biotechnol 97, 5275–5282 (2013). https://doi.org/10.1007/s00253-013-4844-7

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