Microbial metabolism. Part 14. Isolation and bioactivity evaluation of microbial metabolites of resveratrol

Herath, Wimal; Khan, Shabana I.; Khan, Ikhlas A.

doi:10.1080/14786419.2012.722089

Cited by 11 publications

(11 citation statements)

References 24 publications

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“…Thus, these enzymes conjugate various external substrates with methylglucose, although probably for self-defense and not in a synthetic capacity. In addition to the biotransformation of preformed aglycones, in situ biosynthesis of diverse aglycones is also feasible as shown by us for the BDL congeners and for the naphthalenes 57 and 58, and by others for flavonoids (15,58), chalcones and stilbenes (59), or anthraquinones (20). Just as with the BDL congeners, coupling the biosynthesis of such scaffolds with the expression of the GT-MT module in the same chassis would then yield de novo molecules by "total biosynthesis" (60)(61)(62).…”

Section: Discussionmentioning

confidence: 95%

Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis

Xie

Zhang

Wang

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Glycosylation is a prominent strategy to optimize the pharmacokinetic and pharmacodynamic properties of drug-like small-molecule scaffolds by modulating their solubility, stability, bioavailability, and bioactivity. Glycosyltransferases applicable for "sugarcoating" various small-molecule acceptors have been isolated and characterized from plants and bacteria, but remained cryptic from filamentous fungi until recently, despite the frequent use of some fungi for whole-cell biocatalytic glycosylations. Here, we use bioinformatic and genomic tools combined with heterologous expression to identify a glycosyltransferase-methyltransferase (GT-MT) gene pair that encodes a methylglucosylation functional module in the ascomycetous fungus The GT is the founding member of a family nonorthologous to characterized fungal enzymes. Using combinatorial biosynthetic and biocatalytic platforms, we reveal that this GT is a promiscuous enzyme that efficiently modifies a broad range of drug-like substrates, including polyketides, anthraquinones, flavonoids, and naphthalenes. It yields both- and -glucosides with remarkable regio- and stereospecificity, a spectrum not demonstrated for other characterized fungal enzymes. These glucosides are faithfully processed by the dedicated MT to afford 4--methylglucosides. The resulting "unnatural products" show increased solubility, while representative polyketide methylglucosides also display increased stability against glycoside hydrolysis. Upon methylglucosidation, specific polyketides were found to attain cancer cell line-specific antiproliferative or matrix attachment inhibitory activities. These findings will guide genome mining for fungal GTs with novel substrate and product specificities, and empower the efficient combinatorial biosynthesis of a broad range of natural and unnatural glycosides in total biosynthetic or biocatalytic formats.

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Section: Discussionmentioning

confidence: 95%

Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis

Xie

Zhang

Wang

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…However, limited information is available regarding the possible benefit of resveratrol metabolites. Based on current literature, sulfated conjugates partly maintain their bioactivity, but it seems that their activity decreases as the degree of sulfation increases . Interestingly, resveratrol‐3‐ O ‐sulfate, in contrast to unconjugated resveratrol, was found to exert pronounced anti‐estrogen activity in a yeast‐hybrid system with a marked preference for the human estrogen receptors α and β .…”

Section: Metabolism Of Resveratrol and Pterostilbenementioning

confidence: 98%

Metabolism and pharmacokinetics of resveratrol and pterostilbene

2018

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Beneficial properties of resveratrol and pterostilbene, a dimethyl ether analog of resveratrol, have attracted increasing interest in recent years. Resveratrol and pterostilbene exhibit many pharmacological similarities and both of them are generally considered to be safe for human consumption. Beyond the structural and general bioactivity similarities between them, large amounts of data are now available to reveal the metabolic fate and pharmacological differences between them. Pterostilbene was found to be more metabolically stable and usually exhibited stronger pharmacological activities than that of resveratrol. As a contribution to clarify and compare aspects like metabolic stability and pharmacokinetics of resveratrol and pterostilbene, as well as explain the pharmacological similarities and differences between them, this review presents and compares recent data on the metabolism and pharmacokinetics of resveratrol and pterostilbene. © 2018 BioFactors, 44(1):16-25, 2018.

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“…Furthermore, resveratrol-3-O-sulfate mediates the induction of deacetylase sirtuin-1 (SIRT1) and quinone reductase 1 (QR1), but not quinine reductase 2 (QR2). [13][14][15] Interestingly, resveratrol-3-O-sulfate, in contrast to unconjugated resveratrol, was found to exert pronounced anti-estrogen activity in a yeast-hybrid system with a marked preference for the human estrogen receptors ␣ and ␤. 16 Data concerning the biological activity of the resveratrol glucuronides are still scarce.…”

Section: Pharmacological Activity Of Metabolitesmentioning

confidence: 99%

Interplay between metabolism and transport of resveratrol

Maier‐Salamon

Böhmdorfer

Riha

et al. 2013

Annals of the New York Academy of Sciences

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Resveratrol exhibits a variety of biological and pharmacological activities despite its extensive metabolism to sulfates and glucuronides in the intestine and liver. The metabolism of resveratrol is cell specific and strongly correlates with enzyme expression levels. However, a high rate of biotransformation, in concert with the action of the efflux transporters MRP2, MRP3, and ABCG2, reduces intracellular resveratrol concentrations, and may thereby decrease its pharmacological activity. Interestingly, biotransformation is also dependent on disease status. For example, significantly greater sulfation of resveratrol occurs in human breast tumor tissue than in adjacent nonmalignant tissue. The observed differences, however, do not correlate with the expression of sulfotransferases responsible for catalyzing resveratrol sulfation, but rather with significantly higher steroid sulfatase mRNA levels. The in vitro activity of resveratrol sulfates may not necessarily reflect their in vivo function, given the fact that ubiquitously existing human sulfatases can convert the metabolites back to active resveratrol in humans.

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Microbial metabolism. Part 14. Isolation and bioactivity evaluation of microbial metabolites of resveratrol

Cited by 11 publications

References 24 publications

Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis

Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis

Metabolism and pharmacokinetics of resveratrol and pterostilbene

Interplay between metabolism and transport of resveratrol

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