Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Glycosylation of Semi-Synthetic Isoflavene Phenoxodiol with a Recombinant Glycosyltransferase from Micromonospora echinospora ATCC 27932

  • Seo, Minsuk (Transdisciplinary Major in Learning Health Systems, Department of Integrated Biomedical and Life Sciences, Korea University) ;
  • Seol, Yurin (Transdisciplinary Major in Learning Health Systems, Department of Integrated Biomedical and Life Sciences, Korea University) ;
  • Park, Je Won (Department of Integrated Biomedical and Life Sciences, Korea University)
  • Received : 2021.11.18
  • Accepted : 2022.02.05
  • Published : 2022.05.28
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Abstract

Glycosyltransferase (GT)-specific degenerate PCR screening followed by in silico sequence analyses of the target clone was used to isolate a member of family1 GT-encoding genes from the established fosmid libraries of soil actinomycetes Micromonospora echinospora ATCC 27932. A recombinant MeUGT1 was heterologously expressed as a His-tagged protein in E. coli, and its enzymatic reaction with semi-synthetic phenoxodiol isoflavene (as a glycosyl acceptor) and uridine diphosphate-glucose (as a glycosyl donor) created two different glycol-attached products, thus revealing that MeUGT1 functions as an isoflavonoid glycosyltransferase with regional flexibility. Chromatographic separation of product glycosides followed by the instrumental analyses, clearly confirmed these previously unprecedented glycosides as phenoxodiol-4'-α-O-glucoside and phenoxodiol-7-α-O-glucoside, respectively. The antioxidant activities of the above glycosides are almost the same as that of parental phenoxodiol, whereas their anti-proliferative activities are all superior to that of cisplatin (the most common platinum chemotherapy drug) against two human carcinoma cells, ovarian SKOV-3 and prostate DU-145. In addition, they are more water-soluble than their parental aglycone, as well as remaining intractable to the simulated in vitro digestion test, hence demonstrating the pharmacological potential for the enhanced bio-accessibility of phenoxodiol glycosides. This is the first report on the microbial enzymatic biosynthesis of phenoxodiol glucosides.

Keywords

Acknowledgement

This work was supported by Korea University Grant (K1808551).

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