Isomerization of Dihydroquercetin

Kiehlmann, Eberhard; Li, Edmond P. M.

doi:10.1021/np50117a018

Cited by 59 publications

(47 citation statements)

References 16 publications

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“…This unique ring contraction through a 5-exo-trig cyclization is driven by the formation of the thermodynamically favored product 6, while the backward reaction via a 6-endo-trig cyclization to compound 1 is negligible. The catalytic efficacy of CHI becomes apparent when considering the drastic conditions that are required for conversion of a flavanonol, such as taxifolin, to the corresponding auronol, alphitonin, by a nonenzymatic reaction (19,27). For the thermal taxifolin-alphitonin rearrangement at 115°C, monitored over a period of 2 weeks, a half-life for taxifolin of 54 h was determined (19).…”

Section: Discussionmentioning

confidence: 99%

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

et al. 2016

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The enzyme catalyzing the ring-contracting conversion of the flavanonol taxifolin to the auronol alphitonin in the course of flavonoid degradation by the human intestinal anaerobe Eubacterium ramulus was purified and characterized. It stereospecifically catalyzed the isomerization of (؉)-taxifolin but not that of (؊)-taxifolin. The K m for (؉)-taxifolin was 6.4 ؎ 0.8 M, and the V max was 108 ؎ 4 mol min ؊1 (mg protein) ؊1 . The enzyme also isomerized (؉)-dihydrokaempferol, another flavanonol, to maesopsin. Inspection of the encoding gene revealed its complete identity to that of the gene encoding chalcone isomerase (CHI) from E. ramulus. Based on the reported X-ray crystal structure of CHI (M. Gall et al., Angew Chem Int Ed 53:1439 -1442, 2014, http://dx.doi.org/10.1002/anie.201306952), docking experiments suggest the substrate binding mode of flavanonols and their stereospecific conversion. Mutation of the active-site histidine (His33) to alanine led to a complete loss of flavanonol isomerization by CHI, which indicates that His33 is also essential for this activity. His33 is proposed to mediate the stereospecific abstraction of a proton from the hydroxymethylene carbon of the flavanonol C-ring followed by ring opening and recyclization. A flavanonol-isomerizing enzyme was also identified in the flavonoid-converting bacterium Flavonifractor plautii based on its 50% sequence identity to the CHI from E. ramulus. IMPORTANCE Chalcone isomerase was known to be involved in flavone/flavanone conversion by the human intestinal bacterium E. ramulus.Here we demonstrate that this enzyme moreover catalyzes a key step in the breakdown of flavonols/flavanonols. Thus, a single isomerase plays a dual role in the bacterial conversion of dietary bioactive flavonoids. The identification of a corresponding enzyme in the human intestinal bacterium F. plautii suggests a more widespread occurrence of this isomerase in flavonoid-degrading bacteria. F lavonoids represent a major group of plant-derived polyphenolic compounds and have been implicated in beneficial effects on human health (1-4). The flavonoids are classified into several subgroups, which include, among others, flavonols, flavanonols, flavones, flavanones, and chalcones. Quercetin (Fig. 1) is a highly abundant dietary flavonoid that shows a broad range of biological activities. Thus, this flavonol has been intensively studied with respect to its role in disease prevention and use in therapy (5-7). The effects of quercetin and other flavonoids depend on how they are metabolized in the human body, including their conversion by intestinal bacteria (8). Beside deglycosylation and deconjugation, intestinal bacteria are also able to further transform the resulting flavonoid aglycones. However, knowledge about the corresponding bacterial species and, in particular, the enzymes involved is still limited.Eubacterium ramulus and Flavonifractor plautii (formerly Clostridium orbiscindens) are human intestinal bacteria that have been demonstrated to cleave the central heterocyc...

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Section: Discussionmentioning

confidence: 99%

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

et al. 2016

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“…This compound is a minor component in complex (Weidmann 2012). In nature taxifolin is found in French maritime bark (Rohdewald 2002), Douglas fir bark (Kiehlmann and Li 1995), and Siberian larch wood (Ivanova et al 2012) and can be extracted on a commercial scale from the bark and wood, which are the waste products of the forest industry (Ostronkov and Lashin 2012). From this point of view, the use of taxifolin as a lead compound for the design of new biologically active molecules seems to be economical and promising.…”

Section: Introductionmentioning

confidence: 99%

Antioxidant and iron-chelating properties of taxifolin and its condensation product with glyoxylic acid

Shubina

Shatalin

2017

J Food Sci Technol

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The condensation of taxifolin with glyoxylic acid was examined, and the properties of the resulting product were compared with those of taxifolin. The structure of the product was determined by NMR spectroscopy. The ability of the polyphenols to scavenge reactive oxygen species (ROS) was estimated by luminoldependent chemiluminescence. The iron-chelating and iron-reducing activities were studied using absorption spectrophotometry. It was shown that the condensation leads to the formation of a dimer consisting of two taxifolin units linked through a carboxymethine bridge at the C-6 and C-8 positions of the A ring. The dimer exhibited a somewhat higher ROS scavenging activity than taxifolin. The iron-binding capacity of the compounds was proportional to the number of polyphenol units. The iron-reducing ability of the dimer was lower than that of taxifolin. Thus, the dimer possessed a higher antioxidant activity than the parent flavonoid. The data obtained may be useful for a better understanding of processes occurring in foods and beverages and in a search for new active compounds.

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“…A racemic mixture of cis/trans-DHQ was produced by C-2 epimerization of commercial DHQ as reported previously (54). cis-DHQ was purified from the cis/trans-DHQ mixture as follows.…”

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confidence: 99%

Mechanistic Studies on Three 2-Oxoglutarate-dependent Oxygenases of Flavonoid Biosynthesis

Turnbull¹,

Nakajima

Welford³

et al. 2004

Journal of Biological Chemistry

188

154

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Anthocyanidin synthase (ANS), flavonol synthase (FLS), and flavanone 3␤-hydroxylase (FHT) are involved in the biosynthesis of flavonoids in plants and are all members of the family of 2-oxoglutarate-and ferrous iron-dependent oxygenases. ANS, FLS, and FHT are closely related by sequence and catalyze oxidation of the flavonoid "C ring"; they have been shown to have overlapping substrate and product selectivities. In the initial steps of catalysis, 2-oxoglutarate and dioxygen are thought to react at the ferrous iron center producing succinate, carbon dioxide, and a reactive ferryl intermediate, the latter of which can then affect oxidation of the flavonoid substrate.

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Isomerization of Dihydroquercetin

Cited by 59 publications

References 16 publications

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

Chalcone Isomerase from Eubacterium ramulus Catalyzes the Ring Contraction of Flavanonols

Antioxidant and iron-chelating properties of taxifolin and its condensation product with glyoxylic acid

Mechanistic Studies on Three 2-Oxoglutarate-dependent Oxygenases of Flavonoid Biosynthesis

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