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Whole-cell-dependent biosynthesis of sulfo-conjugate using human sulfotransferase expressing budding yeast

Applied Microbiology and Biotechnology volume 102, pages 723–732 (2018)Cite this article

Abstract

Cytosolic sulfotransferases (SULTs), one of the predominant phase II drug metabolizing enzymes (DME), play important roles in metabolism of xeno- and endobiotics to generate their sulfo-conjugates. These sulfo-conjugates often have biological activities but are difficult to study, because even though only small amounts are required to evaluate their efficacy and safety, chemical or biological synthesis of sulfo-conjugatesis is often challenging. Previously, we constructed a DME expression system for cytochrome P450 and UGT, using yeast cells, and successfully produced xenobiotic metabolites in a whole-cell-dependent manner. In this study, we developed a yeast expression system for human SULTs, including SULT1A1, 1A3, 1B1, 1C4, 1E1, and 2A1, in Saccharomyces cerevisiae and examined its sulfo-conjugate productivity. The recombinant yeast cells expressing each of the SULTs successfully produced several hundred milligram per liter of xeno- or endobioticsulfo-conjugates within 6 h. This whole-cell-dependent biosynthesis enabled us to produce sulfo-conjugates without the use of 3’-phosphoadenosine-5’-phosphosulfate, an expensive cofactor. Additionally, the production of regiospecific sulfo-conjugates of several polyphenols was possible with this method, making this novel yeast expression system a powerful tool for uncovering the metabolic pathways and biological actions of sulfo-conjugates.

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Acknowledgements

The study was supported by the JSPSKAKENHI Grant Number JP26292072(SI).

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Authors and Affiliations

  1. Imizu Research Center, TOPUBIO Research Co., Ltd., 5180 Kurokawa, Imizu, Toyama, 939-0351, Japan

    Miyu Nishikawa

  2. Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0351, Japan

    Miyu Nishikawa, Yuuka Masuyama, Motomichi Nunome, Kaori Yasuda, Toshiyuki Sakaki & Shinichi Ikushiro

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  1. Miyu Nishikawa
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  2. Yuuka Masuyama
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  3. Motomichi Nunome
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  4. Kaori Yasuda
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  5. Toshiyuki Sakaki
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  6. Shinichi Ikushiro
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Correspondence to Shinichi Ikushiro.

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Nishikawa, M., Masuyama, Y., Nunome, M. et al. Whole-cell-dependent biosynthesis of sulfo-conjugate using human sulfotransferase expressing budding yeast. Appl Microbiol Biotechnol 102, 723–732 (2018). https://doi.org/10.1007/s00253-017-8621-x

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  • DOI: https://doi.org/10.1007/s00253-017-8621-x

Keywords

  • Sulfotransferase (SULT)
  • Sulfo-conjugate
  • Regioselective biosynthesis
  • Heterologous expression system in yeast
  • Xenobiotic metabolism