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Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides

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논문

Metabolic engineering of Escherichia coli into a versatile glycosylation platform: production of bio-active quercetin glycosides

학술지

Microbial cell factories

저자명

De Bruyn, Frederik; Van Brempt, Maarten; Maertens, Jo; Van Bellegem, Wouter; Duchi, Dries; De Mey, Marjan

초록

<P><B>Background</B></P><P>Flavonoids are bio-active specialized plant metabolites which mainly occur as different glycosides. Due to the increasing market demand, various biotechnological approaches have been developed which use <I>Escherichia coli</I> as a microbial catalyst for the stereospecific glycosylation of flavonoids. Despite these efforts, most processes still display low production rates and titers, which render them unsuitable for large-scale applications.</P><P><B>Results</B></P><P>In this contribution, we expanded a previously developed in vivo glucosylation platform in <I>E. coli</I> W, into an efficient system for selective galactosylation and rhamnosylation. The rational of the novel metabolic engineering strategy constitutes of the introduction of an alternative sucrose metabolism in the form of a sucrose phosphorylase, which cleaves sucrose into fructose and glucose 1-phosphate as precursor for UDP-glucose. To preserve these intermediates for glycosylation purposes, metabolization reactions were knocked-out. Due to the pivotal role of UDP-glucose, overexpression of the interconverting enzymes <I>galE</I> and <I>MUM4</I> ensured the formation of both UDP-galactose and UDP-rhamnose, respectively. By additionally supplying exogenously fed quercetin and overexpressing a flavonol galactosyltransferase (F3GT) or a rhamnosyltransferase (RhaGT), 0.94&nbsp;g/L hyperoside (quercetin 3-<I>O</I>-galactoside) and 1.12&nbsp;g/L quercitrin (quercetin 3-<I>O</I>-rhamnoside) could be produced, respectively. In addition, both strains showed activity towards other promising dietary flavonols like kaempferol, fisetin, morin and myricetin.</P><P><B>Conclusions</B></P><P>Two <I>E. coli</I> W mutants were engineered that could effectively produce the bio-active flavonol glycosides hyperoside and quercitrin starting from the cheap substrates sucrose and quercetin. This novel fermentation-based glycosylation strategy will allow the economically viable production of various glycosides.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s12934-015-0326-1) contains supplementary material, which is available to authorized users.</P>

발행연도

2015

발행기관

BioMed Central

라이선스

cc-by

ISSN

1475-2859

14

페이지

pp.138

주제어

Galactosylation; Rhamnosylation; Glycosylation; Hyperoside; Quercitrin; Escherichia coli W; Metabolic engineering; Flavonoids

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1 2023-12-11

논문; 2015-09-16

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