Metabolic engineering of Escherichia coli for the biosynthesis of flavonoid-O-glucuronides and flavonoid-O-galactoside
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- 作者：So Yeon Kim ; Hye Rin Lee ; Kwang-su Park…
- 关键词：Flavonoid ; O ; glucuronide ; Flavonoid ; O ; galactoside ; Metabolic engineering ; UGT
- 刊名：Applied Microbiology and Biotechnology
- 出版年：2015
- 出版时间：March 2015
- 年：2015
- 卷：99
- 期：5
- 页码：2233-2242
- 全文大小：935 KB
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文摘
Most flavonoids are glycosylated and the nature of the attached sugar can strongly affect their physiological properties. Although many flavonoid glycosides have been synthesized in Escherichia coli, most of them are glucosylated. In order to synthesize flavonoids attached to alternate sugars such as glucuronic acid and galactoside, E. coli was genetically modified to express a uridine diphosphate (UDP)-dependent glycosyltransferase (UGT) specific for UDP-glucuronic acid (AmUGT10 from Antirrhinum majus or VvUGT from Vitis vinifera) and UDP-galactoside (PhUGT from Petunia hybrid) along with the appropriate nucleotide biosynthetic genes to enable simultaneous production of their substrates, UDP-glucuronic acid and UDP-galactose. To engineer UDP-glucuronic acid biosynthesis, the araA gene encoding UDP-4-deoxy-4-formamido-L-arabinose formyltransferase/UDP-glucuronic acid C-4-decarboxylase, which also used UDP-glucuronic acid as a substrate, was deleted in E. coli, and UDP-glucose dehydrogenase (ugd) gene was overexpressed to increase biosynthesis of UDP-glucuronic acid. Using these strategies, luteolin-7-O-glucuronide and quercetin-3-O-glucuronide were biosynthesized to levels of 300 and 687?mg/L, respectively. For the synthesis of quercetin 3-O-galactoside, UGE (encoding UDP-glucose epimerase from Oryza sativa) was overexpressed along with a glycosyltransferase specific for quercetin and UDP-galactose. Using this approach, quercetin 3-O-galactoside was successfully synthesized to a level of 280?mg/L.